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## Protocol Section ### Identification Module **NCT ID:** NCT04188379 **Acronym:** ADVANCE **Brief Title:** A Study to Assess the Efficacy and Safety of Efgartigimod in Adult Patients With Primary Immune Thrombocytopenia (ITP). **Official Title:** A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Efgartigimod (ARGX 113) 10 mg/kg Intravenous in Adult Patients With Primary Immune Thrombocytopenia #### Organization Study ID Info **ID:** ARGX-113-1801 #### Organization **Class:** INDUSTRY **Full Name:** argenx #### Secondary ID Infos **ID:** 2019-002100-41 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2022-02-03 **Type:** ACTUAL #### Disp First Post Date **Date:** 2023-02-09 **Type:** ACTUAL **Disp First Submit Date:** 2023-02-02 **Disp First Submit QC Date:** 2023-02-02 #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-07 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-02-03 **Type:** ACTUAL #### Start Date **Date:** 2019-12-16 **Type:** ACTUAL **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2019-12-05 **Type:** ACTUAL **Study First Submit Date:** 2019-12-04 **Study First Submit QC Date:** 2019-12-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** argenx #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a randomized, double-blind placebo-controlled multicenter phase 3 trial to evaluate the efficacy and safety of ARGX-113 in participants with primary ITP. ### Conditions Module **Conditions:** - Primary Immune Thrombocytopenia **Keywords:** - immune thrombocytopenia - sustained platelet count response - bleeding events ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 131 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patient receiving efgartigimod **Intervention Names:** - Biological: efgartigimod **Label:** efgartigimod **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients receiving placebo **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - efgartigimod **Description:** Intravenous infusion of efgartigimod **Name:** efgartigimod **Other Names:** - ARGX-113 **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Intravenous infusion of placebo **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Proportion of subjects with chronic ITP with a sustained platelet count response was defined as achieving platelet counts of at least 50 × 10\^9 per litre for at least 4 of the 6 visits between weeks 19 and 24 of the study. **Measure:** Proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet counts of at least 50×10E9/L for at least 4 of the 6 visits between week 19 and 24 of the trial. **Time Frame:** Up to five weeks (between visits 19 and 24) #### Secondary Outcomes **Description:** Extent of disease control, defined as the cumulative number of weeks over the planned 24-week treatment period with platelet counts of ≥50 × 10\^9/L in the chronic ITP population. **Measure:** Extent of disease control defined as the number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥50×10E9/L in the chronic ITP population **Time Frame:** Up to 24 weeks (treatment period) **Description:** Proportion of subjects in the overall population achieving platelet counts of at least 50 × 10\^9/L for at least 6 of the 8 visits between weeks 17 and 24 of the study. **Measure:** Proportion of patients in the overall population (chronic and persistent ITP) with a sustained platelet count response defined as achieving platelet counts of at least 50×10E9/L for at least 4 of the 6 visits between week 19 and 24 of the trial **Time Frame:** Up to five weeks (between visits 19 and 24) **Description:** Incidence of the World Health Organization (WHO)-classified bleeding events in the overall population. Analysis was performed on Full Analysis Set population that included all randomized subjects. This secondary endpoint used the WHO-classified bleeding scale. Bleeding was the predominant clinical manifestation of ITP and was typically related to platelet count. Accordingly, measuring bleeding was important for monitoring this subject population. The WHO bleeding scale was neither specific to nor validated for ITP, but had been implemented in ITP clinical studies; no specific and validated tools for assessing bleeding in ITP were available. **Measure:** Incidence and severity of the WHO-classified bleeding events **Time Frame:** Up to 24 weeks (From Week 1 to Week 24) **Description:** Proportion of subjects in the overall population (chronic and persistent ITP) with a sustained platelet count response, defined as achieving platelet counts of at least 50 × 10\^9/L for at least 4 of the 6 visits between weeks 19 and 24 of the study. The analysis was performed on Full Analysis set population that included all randomized subjects in the study. **Measure:** Proportion of patients in the overall population achieving platelet counts of at least 50 x 10^9/L for at least 6 of the 8 visits between week 17 and 24 of the trial. **Time Frame:** Up to 7 weeks (between visits 17 and 24) ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * Ability to understand the requirements of the trial, to provide written informed consent (including consent for the use and disclosure of research-related health information), and to comply with the trial protocol procedures (including required trial visits). * Male or female patient aged ≥18 years. * Confirmed ITP diagnosis, at least 3 months before randomization and according to the American Society of Hematology Criteria, and no known other etiology for thrombocytopenia. * Diagnosis supported by a response to a prior ITP therapy (other than thrombopoietin receptor agonists \[TPO-RAs\]), in the opinion of the investigator. * Mean platelet count of \<30×10E9/L from 2 counts: 1 platelet count collected during the screening period and the predose platelet count on the day of randomization. * At the start of the trial, the patient is either on concurrent ITP treatment(s) and has received at least 1 prior therapy for ITP in the past, or the patient is not on treatment for ITP but has received at least 2 prior treatments for ITP. Patients receiving permitted concurrent ITP treatment(s) at baseline, must have been stable in dose and frequency for at least 4 weeks prior to randomization. * Women of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline before trial medication (infusion) can be administered. * Women of childbearing potential should use a highly effective or acceptable method of contraception during the trial and for 90 days after the last administration of the IMP. Exclusion criteria: * ITP/thrombocytopenia associated with another condition, eg, lymphoma, chronic lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune thrombocytopenia, or thrombocytopenia associated with myeloid dysplasia. * Use of certain medications before the start of the studies (more details in the protocol) * Patients who have a history of malignancy, including malignant thymoma, or myeloproliferative or lymphoproliferative disorders, unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before screening. Patients with completely excised non-melanoma skin cancer (such as basal cell carcinoma or squamous cell carcinoma) or cervical carcinoma in situ would be permitted at any time. * Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments. * History of any major thrombotic or embolic event within 12 months prior to randomization. * History of coagulopathy or hereditary thrombocytopenia or a family history of thrombocytopenia. * History of a recent or planned major surgery (that involves major organs eg, brain, heart, lung, liver, bladder, or gastrointestinal tract) within 4 weeks of randomization. * Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) * Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than ITPdespite appropriate treatments which could put the patient at undue risk. * Patients with known medical history of hypersensitivity to any of the ingredients of the IMP. * Patients who previously participated in a clinical trial with efgartigimod and have received at least 1 administration of the IMP. * Pregnant or lactating females. More details in the protocol **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tucson **Country:** United States **Facility:** Investigator Site 0010038 **State:** Arizona **Zip:** 85711 **Location 2:** **City:** Washington **Country:** United States **Facility:** Investigator Site 0010045 **State:** District of Columbia **Zip:** 20007 **Location 3:** **City:** Jacksonville **Country:** United States **Facility:** Investigator Site 0010034 **State:** Florida **Zip:** 32204 **Location 4:** **City:** Ocala **Country:** United States **Facility:** Investigator site 0010037 **State:** Florida **Zip:** 34474 **Location 5:** **City:** Iowa City **Country:** United States **Facility:** Investigator Site 0010042 **State:** Iowa **Zip:** 52242 **Location 6:** **City:** Greenville **Country:** United States **Facility:** Investigator Site 0010046 **State:** North Carolina **Zip:** 27834 **Location 7:** **City:** Cleveland **Country:** United States **Facility:** Investigator Site 0010049 **State:** Ohio **Zip:** 44106 **Location 8:** **City:** Columbus **Country:** United States **Facility:** Investigator Site 0010040 **State:** Ohio **Zip:** 44106 **Location 9:** **City:** Philadelphia **Country:** United States **Facility:** Investigator Site 0010041 **State:** Pennsylvania **Zip:** 19104 **Location 10:** **City:** Linz **Country:** Austria **Facility:** Investigator Site 0430004 **Location 11:** **City:** Vienna **Country:** Austria **Facility:** Investigator Site 0430002 **Location 12:** **City:** Vienna **Country:** Austria **Facility:** Investigator Site 0430003 **Location 13:** **City:** Brasschaat **Country:** Belgium **Facility:** Investigator Site 0320012 **Location 14:** **City:** Brugge **Country:** Belgium **Facility:** Investigator Site 0320011 **Location 15:** **City:** Leuven **Country:** Belgium **Facility:** Investigator Site 0320015 **Location 16:** **City:** Turnhout **Country:** Belgium **Facility:** Investigator Site 0320014 **Location 17:** **City:** Verviers **Country:** Belgium **Facility:** Investigator Site 0320020 **Location 18:** **City:** Yvoir **Country:** Belgium **Facility:** Investigator site 0320002 **Location 19:** **City:** Pleven **Country:** Bulgaria **Facility:** Investigator Site 3590001 **Location 20:** **City:** Sofia **Country:** Bulgaria **Facility:** Investigator Site 3590002 **Location 21:** **City:** Brno **Country:** Czechia **Facility:** Investigator Site 4200001 **Location 22:** **City:** Olomouc **Country:** Czechia **Facility:** Investigator Site 4200008 **Location 23:** **City:** Ostrava **Country:** Czechia **Facility:** Investigator Site 4200006 **Location 24:** **City:** Praha **Country:** Czechia **Facility:** Investigator Site 4200007 **Location 25:** **City:** Clermont-Ferrand **Country:** France **Facility:** Investigator Site 0330019 **Location 26:** **City:** Créteil **Country:** France **Facility:** Investigator Site 0330009 **Location 27:** **City:** Le Mans **Country:** France **Facility:** Investigator Site 0330015 **Location 28:** **City:** Montpellier **Country:** France **Facility:** Investigator Site 0330018 **Location 29:** **City:** Pessac **Country:** France **Facility:** Investigator Site 0330008 **Location 30:** **City:** Périgueux **Country:** France **Facility:** Investigator Site 0330016 **Location 31:** **City:** Rouen **Country:** France **Facility:** Investigator Site 0330017 **Location 32:** **City:** Tbilisi **Country:** Georgia **Facility:** Investigator Site 9950006 **Location 33:** **City:** Tbilisi **Country:** Georgia **Facility:** Investigator Site 9950007 **Location 34:** **City:** Tbilisi **Country:** Georgia **Facility:** Investigator Site 9950008 **Location 35:** **City:** Tbilisi **Country:** Georgia **Facility:** Investigator Site 9950009 **Location 36:** **City:** Tbilisi **Country:** Georgia **Facility:** Investigator Site 9950011 **Location 37:** **City:** Tbilisi **Country:** Georgia **Facility:** Investigator Site 9950012 **Location 38:** **City:** Düsseldorf **Country:** Germany **Facility:** Investigator Site 0490010 **Location 39:** **City:** Essen **Country:** Germany **Facility:** Investigator Site 0490008 **Location 40:** **City:** Gießen **Country:** Germany **Facility:** Investigator Site 0490012 **Location 41:** **City:** Budapest **Country:** Hungary **Facility:** Investigator Site 0360004 **Location 42:** **City:** Debrecen **Country:** Hungary **Facility:** Investigator Site 0360006 **Location 43:** **City:** Győr **Country:** Hungary **Facility:** Investigator Site 0360015 **Location 44:** **City:** Nyiregyhaza **Country:** Hungary **Facility:** Investigator site 0360010 **Location 45:** **City:** Szombathely **Country:** Hungary **Facility:** Investigator Site 0360014 **Location 46:** **City:** Campobasso **Country:** Italy **Facility:** Investigator Site 0390012 **Location 47:** **City:** Milan **Country:** Italy **Facility:** Investigator Site 0390014 **Location 48:** **City:** Monza **Country:** Italy **Facility:** Investigator Site 0390020 **Location 49:** **City:** Novara **Country:** Italy **Facility:** Investigator Site 0390015 **Location 50:** **City:** Ravenna **Country:** Italy **Facility:** Investigator Site 0390010 **Location 51:** **City:** Reggio Calabria **Country:** Italy **Facility:** Investigator Site 0390011 **Location 52:** **City:** Reggio Emilia **Country:** Italy **Facility:** Investigator Site 0390018 **Location 53:** **City:** Rimini **Country:** Italy **Facility:** Investigator Site 0390019 **Location 54:** **City:** Roma **Country:** Italy **Facility:** Investigator Site 0390021 **Location 55:** **City:** Siena **Country:** Italy **Facility:** Investigator Site 0390009 **Location 56:** **City:** Torino **Country:** Italy **Facility:** Investigator Site 0390017 **Location 57:** **City:** Trieste **Country:** Italy **Facility:** Investigator Site 0390016 **Location 58:** **City:** Bunkyō-Ku **Country:** Japan **Facility:** Investigator Site 0810024 **Location 59:** **City:** Hirakata **Country:** Japan **Facility:** Investigator Site 0810015 **Location 60:** **City:** Hiroshima **Country:** Japan **Facility:** Investigator Site 0810010 **Location 61:** **City:** Iruma **Country:** Japan **Facility:** Investigator site 0810017 **Location 62:** **City:** Isehara **Country:** Japan **Facility:** Investigator site 0810011 **Location 63:** **City:** Kashiwa **Country:** Japan **Facility:** Investigator Site 0810022 **Location 64:** **City:** Maebashi **Country:** Japan **Facility:** Investigator site 0810018 **Location 65:** **City:** Minato-Ku **Country:** Japan **Facility:** Investigator site 0810020 **Location 66:** **City:** Niigata **Country:** Japan **Facility:** Investigator Site 0810021 **Location 67:** **City:** Sapporo **Country:** Japan **Facility:** Investigator site 0810014 **Location 68:** **City:** Shibukawa **Country:** Japan **Facility:** Investigator site 0810016 **Location 69:** **City:** Shimotsuke **Country:** Japan **Facility:** Investigator Site 0810023 **Location 70:** **City:** Shinjuku-Ku **Country:** Japan **Facility:** Investigator Site 0810025 **Location 71:** **City:** Den Haag **Country:** Netherlands **Facility:** Investigator site 0310006 **Location 72:** **City:** Rotterdam **Country:** Netherlands **Facility:** Investigator Site 0310005 **Location 73:** **City:** Rotterdam **Country:** Netherlands **Facility:** Investigator Site 0310007 **Location 74:** **City:** Białystok **Country:** Poland **Facility:** Investigator Site 0480030 **Location 75:** **City:** Brzozów **Country:** Poland **Facility:** Investigator Site 0480015 **Location 76:** **City:** Bydgoszcz **Country:** Poland **Facility:** Investigator Site 0480010 **Location 77:** **City:** Chorzów **Country:** Poland **Facility:** Investigator Site 0480013 **Location 78:** **City:** Gdańsk **Country:** Poland **Facility:** Investigator Site 0480012 **Location 79:** **City:** Katowice **Country:** Poland **Facility:** Investigator Site 0480008 **Location 80:** **City:** Lodz **Country:** Poland **Facility:** Investigator Site 0480011 **Location 81:** **City:** Lublin **Country:** Poland **Facility:** Investigator Site 0480014 **Location 82:** **City:** Nowy Sącz **Country:** Poland **Facility:** Investigator site 0480026 **Location 83:** **City:** Wrocław **Country:** Poland **Facility:** Investigator Site 0480016 **Location 84:** **City:** Kaluga **Country:** Russian Federation **Facility:** Investigator site 0070006 **Location 85:** **City:** Petrozavodsk **Country:** Russian Federation **Facility:** Investigator Site 0070007 **Location 86:** **City:** Rostov-on-Don **Country:** Russian Federation **Facility:** Investigator Site 0070013 **Location 87:** **City:** Syktyvkar **Country:** Russian Federation **Facility:** Investigator Site 0070015 **Location 88:** **City:** Tula **Country:** Russian Federation **Facility:** Investigator Site 0070012 **Location 89:** **City:** Ufa **Country:** Russian Federation **Facility:** Investigator site 0070010 **Location 90:** **City:** Barcelona **Country:** Spain **Facility:** Investigator Site 0340006 **Location 91:** **City:** Barcelona **Country:** Spain **Facility:** Investigator Site 0340007 **Location 92:** **City:** Burgos **Country:** Spain **Facility:** Investigator Site 0340030 **Location 93:** **City:** Madrid **Country:** Spain **Facility:** Investigator Site 0340009 **Location 94:** **City:** Madrid **Country:** Spain **Facility:** Investigator Site 0340014 **Location 95:** **City:** Madrid **Country:** Spain **Facility:** Investigator Site 0340015 **Location 96:** **City:** Palma De Mallorca **Country:** Spain **Facility:** Investigator site 0340012 **Location 97:** **City:** Sevilla **Country:** Spain **Facility:** Investigator Site 0340013 **Location 98:** **City:** Valencia **Country:** Spain **Facility:** Investigator Site 0340004 **Location 99:** **City:** Valencia **Country:** Spain **Facility:** Investigator Site 0340011 **Location 100:** **City:** Adana **Country:** Turkey **Facility:** Investigator Site 0900002 **Location 101:** **City:** Adapazarı **Country:** Turkey **Facility:** Investigator Site 0900007 **Location 102:** **City:** Ankara **Country:** Turkey **Facility:** Investigator Site 0900003 **Location 103:** **City:** Ankara **Country:** Turkey **Facility:** Investigator Site 0900006 **Location 104:** **City:** Ankara **Country:** Turkey **Facility:** Investigator Site 0900008 **Location 105:** **City:** Ankara **Country:** Turkey **Facility:** Investigator Site 0900015 **Location 106:** **City:** Edirne **Country:** Turkey **Facility:** Investigator Site 0900016 **Location 107:** **City:** Istanbul **Country:** Turkey **Facility:** Investigator Site 0900013 **Location 108:** **City:** Izmir **Country:** Turkey **Facility:** Investigator Site 0900004 **Location 109:** **City:** Kocaeli **Country:** Turkey **Facility:** Investigator Site 0900014 **Location 110:** **City:** Malatya **Country:** Turkey **Facility:** Investigator Site 0900018 **Location 111:** **City:** Manisa **Country:** Turkey **Facility:** Investigator Site 0900005 **Location 112:** **City:** Mersin **Country:** Turkey **Facility:** Investigator Site 0900010 **Location 113:** **City:** Samsun **Country:** Turkey **Facility:** Investigator Site 0900009 **Location 114:** **City:** Tekirdağ **Country:** Turkey **Facility:** Investigator Site 0900017 **Location 115:** **City:** Trabzon **Country:** Turkey **Facility:** Investigator Site 0900019 **Location 116:** **City:** Kharkiv **Country:** Ukraine **Facility:** Investigator Site 3800022 **Location 117:** **City:** Mykolayiv **Country:** Ukraine **Facility:** Investigator site 3800006 **Location 118:** **City:** London **Country:** United Kingdom **Facility:** Investigator Site 0440008 **Location 119:** **City:** Rhyl **Country:** United Kingdom **Facility:** Investigator Site 0440010 **Location 120:** **City:** Southampton **Country:** United Kingdom **Facility:** Investigator Site 0440012 **Location 121:** **City:** Truro **Country:** United Kingdom **Facility:** Investigator Site 0440014 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001791 - Term: Blood Platelet Disorders - ID: D000006402 - Term: Hematologic Diseases - ID: D000095542 - Term: Cytopenia - ID: D000011696 - Term: Purpura, Thrombocytopenic - ID: D000011693 - Term: Purpura - ID: D000001778 - Term: Blood Coagulation Disorders - ID: D000057049 - Term: Thrombotic Microangiopathies - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases - ID: D000006470 - Term: Hemorrhage - ID: D000010335 - Term: Pathologic Processes - ID: D000012877 - Term: Skin Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: LOW - As Found: Unknown - ID: M16680 - Name: Thrombocytopenia - Relevance: HIGH - As Found: Thrombocytopenia - ID: M18945 - Name: Purpura, Thrombocytopenic, Idiopathic - Relevance: HIGH - As Found: Immune Thrombocytopenia - ID: M14547 - Name: Purpura - Relevance: LOW - As Found: Unknown - ID: M14550 - Name: Purpura, Thrombocytopenic - Relevance: LOW - As Found: Unknown - ID: M5072 - Name: Blood Platelet Disorders - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M3170 - Name: Cytopenia - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M28682 - Name: Thrombotic Microangiopathies - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M15680 - Name: Skin Manifestations - Relevance: LOW - As Found: Unknown - ID: T3021 - Name: Immune Thrombocytopenia - Relevance: HIGH - As Found: Immune Thrombocytopenia - ID: T3007 - Name: Idiopathic Thrombocytopenic Purpura - Relevance: HIGH - As Found: Primary Immune Thrombocytopenia ### Condition Browse Module - Meshes - ID: D000013921 - Term: Thrombocytopenia - ID: D000016553 - Term: Purpura, Thrombocytopenic, Idiopathic ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT06315179 **Acronym:** STRIDE **Brief Title:** Seattle Spatial Transcriptomic Research in Inflammatory Bowel Disease Evaluation (STRIDE) **Official Title:** Seattle Spatial Transcriptomic Research in Inflammatory Bowel Disease Evaluation #### Organization Study ID Info **ID:** STUDY00004616 #### Organization **Class:** OTHER **Full Name:** Seattle Children's Hospital ### Status Module #### Completion Date **Date:** 2030-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-19 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-15 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2028-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-04 **Type:** ESTIMATED **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2024-03-18 **Type:** ACTUAL **Study First Submit Date:** 2024-03-05 **Study First Submit QC Date:** 2024-03-11 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Allen Institute #### Lead Sponsor **Class:** OTHER **Name:** Seattle Children's Hospital #### Responsible Party **Investigator Affiliation:** Seattle Children's Hospital **Investigator Full Name:** Betty Zheng **Investigator Title:** Assistant Professor, Director of Advanced IBD Fellowship Program **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a prospective observational study collecting long-term clinical data and samples for research in pediatric inflammatory bowel disease (IBD) patients with gut inflammation and a control cohort of pediatric patients with disorders of the brain-gut interactions (DBGI) with no detectable gut inflammation. **Detailed Description:** Research procedures will coincide with clinical visits at institutional standards. As part of their clinical disease evaluation, participants will have blood, stool, and tissue collected as indicated by their disease course. Additional research samples or data will be collected during these visits. Participants will be asked to collect urine samples specifically for research. ### Conditions Module **Conditions:** - Inflammatory Bowel Diseases - Crohn Disease - Ulcerative Colitis - Indeterminate Colitis - Functional Abdominal Pain Syndrome - Functional Bowel Disorder - Esophageal Diseases - Gastroduodenal Disorder - Bowel Dysfunction - Gallbladder Diseases - Sphincter of Oddi Dysfunction - Anorectal Disorder **Keywords:** - IBD - DGBI ### Design Module #### Bio Spec **Description:** -The blood and tissue bio-specimens obtained for this research will undergo genetic testing including but not limited to single-cell analysis, exome sequencing, and whole genome sequencing, gene editing, and organoid generation (results will not be provided to participants and/or their care providers). Cells are not 'immortalized' and will eventually expire. **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 3 Years ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will enroll before their initial diagnostic procedure. After pathology results are reported, participants will be categorized based on the assigned diagnoses: Inflammatory Bowel Disease (IBD) \[Crohn's disease (CD), ulcerative colitis (UC), and Indeterminate Colitis (IC)\] vs Disorders of the Brain-Gut Interactions (DGBI). Participation in the IBD cohort will last for three years. **Intervention Names:** - Diagnostic Test: Esophagogastroduodenoscopy (EGD) with biopsy - Diagnostic Test: Colonoscopy w/ biopsy **Label:** Inflammatory Bowel Disease #### Arm Group 2 **Description:** Participants will enroll before their initial diagnostic procedure. After pathology results are reported, participants will be categorized based on the assigned diagnoses: Inflammatory Bowel Disease (IBD) \[Crohn's disease (CD), ulcerative colitis (UC), and Indeterminate Colitis (IC)\] vs Disorders of the Brain-Gut Interactions (DGBI). -The DGBI cohort will be subdivided into: Esophageal Disorder, Gastroduodenal Disorder, Bowel Disorder, Centrally Mediated Disorders of GI Pain, Gallbladder and Sphincter of Oddi Disorder, Anorectal Disorder, Childhood Functional GI Disorders: Neonate/Toddler, Childhood Functional GI Disorders: Child/Adolescent Participation in the DGBI cohort will include the initial sample and data collection as well an one further medical record extraction at month 24. **Intervention Names:** - Diagnostic Test: Esophagogastroduodenoscopy (EGD) with biopsy - Diagnostic Test: Colonoscopy w/ biopsy **Label:** Disorders of the Brain-Gut Interactions ### Interventions #### Intervention 1 **Arm Group Labels:** - Disorders of the Brain-Gut Interactions - Inflammatory Bowel Disease **Description:** Esophagogastroduodenoscopy (EGD) is a test procedure to examine the lining of the esophagus, stomach, and first part of the small intestine. **Name:** Esophagogastroduodenoscopy (EGD) with biopsy **Type:** DIAGNOSTIC_TEST #### Intervention 2 **Arm Group Labels:** - Disorders of the Brain-Gut Interactions - Inflammatory Bowel Disease **Description:** Colonoscopy is a test procedure to examine the lining of the different portions of the large intestine: cecum, colon, rectum, and anal canal. **Name:** Colonoscopy w/ biopsy **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Collection of blood and stool samples at baseline month 1, month 2, month 3, month 6, month 12, month 24, and month 36. Tissue will be collected at baseline and at any follow-up endoscopy or surgical intervention. **Measure:** Bio-repository sample collection for spatial transcriptomics **Time Frame:** 3 years #### Secondary Outcomes **Description:** * Age at diagnosis * Location of disease: distal 1/3 +- ileum limited cecal disease, colonic, ileocolonic, upper disease proximal to ligament of treitz, upper disease distal to ligament of treitz and proximal to distal 1/3 ileum * Behavior of disease: non-stricturing/non-penetrating, stricturing, penetrating, both penetrating and stricturing disease, either at the same or different times * Perianal sub type: yes, no, do not know * Growth sub type: no evidence of growth delay, growth delay **Measure:** Paris Classification of Crohn's Disease **Time Frame:** Baseline **Description:** * Age at diagnosis * Location of disease: terminal ileal +- limited cecal disease, colonic, ileocolonic, isolated upper disease * Behavior of disease: non-stricturing/non-penetrating, stricturing, penetrating, both penetrating and stricturing disease, either at the same or different times **Measure:** Montreal Classification of Crohn's disease **Time Frame:** Baseline **Description:** * Extent of disease: ulcerative proctitis, left-sided UC (distal to splenic flexure), extensive (hepatic flexure distally), pancolitis (proximal to hepatic flexure) * Severity: never severe, ever severe **Measure:** Paris Classification of Ulcerative Colitis/Indeterminate Colitis **Time Frame:** Baseline **Description:** * Extent of disease: ulcerative proctitis, left-sided UC (distal to splenic flexure), extensive (proximal to splenic flexure) * Severity: clinical remission, mild UC, moderate UC, severe UC **Measure:** Montreal Classification of Ulcerative Colitis/Indeterminate Colitis **Time Frame:** Baseline **Description:** Diagnoses super-type and applicable sub type: * Esophageal Disorders * Gastroduodenal Disorder * Bowel Disorder * Centrally Mediated Disorders of GI Pain * Gallbladder and Sphincter of Oddi Disorder * Anorectal Disorder * Childhood Functional GI Disorders: Neonate/Toddler * Childhood Functional GI Disorders: Child/Adolescent **Measure:** Disorder of Gut-Brain Interaction classification **Time Frame:** Baseline **Description:** Severity: Quiescent, Mild, Moderate, Severe **Measure:** Physician's Global Assessment (PGA) **Time Frame:** 3 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Suspected diagnosis of CD (Crohn's Disease), UC (Ulcerative Colitis) or Indeterminate colitis (IC) Exclusion Criteria: * Evidence of Other Complicating Medical Issues: * Other serious medical conditions, such as neurological, liver, kidney, or systemic disease * Pregnancy * Tobacco, alcohol, or illicit drug abuse **Maximum Age:** 21 Years **Minimum Age:** 6 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT **Study Population:** All individuals who meet inclusion criteria will be approached. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mason E Nuding, BS **Phone:** 206-987-0055 **Role:** CONTACT #### Locations **Location 1:** **City:** Seattle **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mason E Nuding - **Phone:** 206-987-0055 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Clinical Research Coordinator - **Phone:** 206-987-2521 - **Role:** CONTACT ***Contact 3:*** - **Name:** Hengqi Zheng, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Seattle Children's Hospital **State:** Washington **Zip:** 98105 #### Overall Officials **Official 1:** **Affiliation:** Seattle Children's Hospital, University of Washington **Name:** Betty (Hengqi) Zheng, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005759 - Term: Gastroenteritis - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000003108 - Term: Colonic Diseases - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations - ID: D000012817 - Term: Signs and Symptoms, Digestive - ID: D000001660 - Term: Biliary Tract Diseases - ID: D000001657 - Term: Biliary Dyskinesia - ID: D000003137 - Term: Common Bile Duct Diseases - ID: D000001649 - Term: Bile Duct Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M6638 - Name: Crohn Disease - Relevance: HIGH - As Found: Crohn's Disease - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: HIGH - As Found: Bowel Disease - ID: M17917 - Name: Inflammatory Bowel Diseases - Relevance: HIGH - As Found: Inflammatory Bowel Disease - ID: M6320 - Name: Colitis - Relevance: HIGH - As Found: Colitis - ID: M18311 - Name: Abdominal Pain - Relevance: HIGH - As Found: Abdominal Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M6321 - Name: Colitis, Ulcerative - Relevance: LOW - As Found: Unknown - ID: M17206 - Name: Ulcer - Relevance: LOW - As Found: Unknown - ID: M8085 - Name: Esophageal Diseases - Relevance: HIGH - As Found: Esophageal Diseases - ID: M8823 - Name: Gallbladder Diseases - Relevance: HIGH - As Found: Gallbladder Diseases - ID: M25690 - Name: Sphincter of Oddi Dysfunction - Relevance: HIGH - As Found: Sphincter of Oddi Dysfunction - ID: M14844 - Name: Rectal Diseases - Relevance: HIGH - As Found: Anorectal Disorder - ID: M8875 - Name: Gastroenteritis - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M6336 - Name: Colonic Diseases - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M15622 - Name: Signs and Symptoms, Digestive - Relevance: LOW - As Found: Unknown - ID: M4946 - Name: Biliary Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M22574 - Name: Dyskinesias - Relevance: LOW - As Found: Unknown - ID: M4943 - Name: Biliary Dyskinesia - Relevance: LOW - As Found: Unknown - ID: M4935 - Name: Bile Duct Diseases - Relevance: LOW - As Found: Unknown - ID: M6364 - Name: Common Bile Duct Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003424 - Term: Crohn Disease - ID: D000003092 - Term: Colitis - ID: D000007410 - Term: Intestinal Diseases - ID: D000015212 - Term: Inflammatory Bowel Diseases - ID: D000004935 - Term: Esophageal Diseases - ID: D000005705 - Term: Gallbladder Diseases - ID: D000012002 - Term: Rectal Diseases - ID: D000046628 - Term: Sphincter of Oddi Dysfunction - ID: D000015746 - Term: Abdominal Pain ### Intervention Browse Module - Browse Branches - Abbrev: HB - Name: Herbal and Botanical - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T120 - Name: Cola - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05680779 **Brief Title:** Neuromodulation in Chronic Ankle Instability **Official Title:** Ultrasound-guided Percutaneous Neuromodulation in Patiens With Chronic Ankle Instability #### Organization Study ID Info **ID:** CEID/2022/2/031 #### Organization **Class:** OTHER **Full Name:** University of Alcala ### Status Module #### Completion Date **Date:** 2024-05-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-03 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2024-05-02 **Type:** ACTUAL #### Start Date **Date:** 2023-07-23 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2023-01-11 **Type:** ACTUAL **Study First Submit Date:** 2022-12-23 **Study First Submit QC Date:** 2022-12-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Alcala #### Responsible Party **Investigator Affiliation:** University of Alcala **Investigator Full Name:** Prof. Dr. Daniel Pecos Martín **Investigator Title:** PhD Daniel Pecos-Martin **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Ankle sprain is a common injury. Around 712,000 sprains occur every day in the world. It is estimated that they account for 45% of sports injuries, being the second part of the body that is most frequently injured in sports. Of the patients who suffer this injury, around 70% will develop chronic ankle instability, a situation that can cause residual pain, recurrent sprains, a feeling of lack of stability and decreased physical activity. Two entities can be included in chronic ankle instability: mechanical instability, which involves movement of the joint beyond its physiological limit, and functional instability, which includes proprioceptive dysfunction, impaired neuromuscular control, postural control, and strength deficits. Currently, the conservative treatment of these patients consists of neuromuscular training through the use of dynamic balance platforms, taping, joint mobilization, dry needling, and the use of plantar supports, balance training being the one that has shown the best result. Ultrasound-guided percutaneous neuromodulation (PNM) is a recently used technique in the field of invasive physiotherapy that consists of applying a square wave biphasic electrical current through an acupuncture needle-like electrode that is place in close proximity to the nerve with ultrasound guidance. The aim of this study is to evaluate the effectiveness of PNM in ankle instability. ### Conditions Module **Conditions:** - Ankle Sprains ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects were treated once time. The technique consisted in the application of a square wave biphasic electrical current, with 10 Hz frequency, with 250 μs pulse width and the maximal torelable intensity to cause an exacerbated muscle contraction during ten seconds with a rest period of another ten seconds y total number of ten times. The subjects were lying in lateral decubitus. The common peroneal nerve was located with ultrasound (cross section) near to the peroneal head. After, an acupuncture needle (0,30mm x 30mm) was inserted in a long axis approach until the perineurium of the common peroneal nerve (in close proximity) **Intervention Names:** - Other: ultrasound-guided percutaneous neuromodulation **Label:** PNM group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subjects were treated once time. The subjects were lying in lateral decubitus. The common peroneal nerve was located with ultrasound (cross section) near to the peroneal head. After, an acupuncture needle (0,30mm x 30mm) was inserted in a long axis approach until the perineurium of the common peroneal nerve (in close proximity). The needle remains in this location during 200 seconds without any electrical current. **Intervention Names:** - Other: dry needling **Label:** Control group **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - PNM group **Description:** It´s an intervention of physiotherapy **Name:** ultrasound-guided percutaneous neuromodulation **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Control group **Description:** It´s an intervention of physiotherapy **Name:** dry needling **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The Cumberland ankle instability tool (CAIT) is a questionnaire that consists of 9 items, the maximum score of the questionnaire is 30 points, the lower the score obtained, the more severe the functional instability of the ankle. The Spanish version of the CAIT has high internal consistency (Cronbach's α00.766) and reliability (intraclass correlation coefficient 0.979, 95 % confidence interval (CI) 0.958-0.990). **Measure:** Cumberland ankle instability tool **Time Frame:** Change from Baseline up to three months #### Secondary Outcomes **Description:** The BBS is a platform designed to measure and record an individual´s ability to maintain stability under dynamic stress. It calculates a medial-lateral stability index (MLSI), anterior-posterior stability index (APSI), and an overall stability index (OSI) with reliability estimates of R= 0.92 (OSI), R = 0.89 (APSI), R= 0.93 (MLSI). **Measure:** Byodex Balance System (BBS) **Time Frame:** Change from Baseline up to 5 minutes **Description:** Mdurance EMG system is valid tool to measure muscle activity during isokinetic contractions. It has shown an almost perfect Intraclass Correlation Coefficient\>0.81. **Measure:** Electromyography muscle (EMG) **Time Frame:** Change from Baseline up to 5 minutes **Description:** Myoton Pro is a device designed to measure and record Oscillation frequency (pitch), dynamic stiffness (stiffness), logarithmic decrement (elasticity), mechanical stress relaxation time and creep. It has shown an excellent reliability, Intraclass Correlation Coefficient 0.91-0.96 in all measures with the exception of elasticity 0.78-0.86 **Measure:** stiffness tissue **Time Frame:** Change from Baseline up to 5 minutes ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Ankle instability Exclusion Criteria: * Subjects taking NSAIDs, analgesics or muscle relaxants * Epilepsy * Belonephobia or allergy to metals **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Alcalá de Henares **Country:** Spain **Facility:** Physioterapy and Pain center research **State:** Madrid **Zip:** 28805 #### Overall Officials **Official 1:** **Affiliation:** Alcala University **Name:** Daniel Pecos-Martin, PhD **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007869 - Term: Leg Injuries - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M18909 - Name: Ankle Injuries - Relevance: HIGH - As Found: Ankle Sprain - ID: M10881 - Name: Leg Injuries - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000016512 - Term: Ankle Injuries ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03304379 **Acronym:** FACT OA2 **Brief Title:** Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip **Official Title:** Phase 3 Randomized, Double-Blind, Multi-Dose, Placebo And NSAID Controlled Study To Evaluate The Efficacy And Safety Of Fasinumab In Patients With Pain Due To Osteoarthritis Of The Knee Or Hip #### Organization Study ID Info **ID:** R475-OA-1688 #### Organization **Class:** INDUSTRY **Full Name:** Regeneron Pharmaceuticals #### Secondary ID Infos **ID:** 2017-001702-15 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2020-11-09 **Type:** ACTUAL #### Disp First Post Date **Date:** 2023-02-24 **Type:** ACTUAL **Disp First Submit Date:** 2020-12-11 **Disp First Submit QC Date:** 2023-01-30 #### Expanded Access Info #### Last Update Post Date **Date:** 2023-02-24 **Type:** ACTUAL **Last Update Submit Date:** 2023-01-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-12-13 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-02-24 **Type:** ACTUAL **Results First Submit Date:** 2022-12-09 **Results First Submit QC Date:** 2023-01-30 #### Start Date **Date:** 2017-10-26 **Type:** ACTUAL **Status Verified Date:** 2023-01 #### Study First Post Date **Date:** 2017-10-09 **Type:** ACTUAL **Study First Submit Date:** 2017-10-02 **Study First Submit QC Date:** 2017-10-05 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Teva Pharmaceutical Industries, Ltd. #### Lead Sponsor **Class:** INDUSTRY **Name:** Regeneron Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The primary objective of the study is to evaluate the efficacy of fasinumab compared to placebo, when administered for up to 24 weeks in patients with pain due to osteoarthritis (OA) of the knee or hip. The secondary objectives of the study are: * To evaluate the efficacy of fasinumab compared to non-steroidal anti-inflammatory drugs (NSAID)s, when administered for up to 24 weeks in patients with pain due to OA of the knee or hip * To assess the safety and tolerability of fasinumab compared to placebo and compared to NSAIDs, when administered for up to 24 weeks in patients with pain due to OA of the knee or hip ### Conditions Module **Conditions:** - Osteoarthritis, Knee - Osteoarthritis, Hip ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1650 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Fasinumab - Drug: Matching placebo **Label:** Dosing regimen 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Other: Diclofenac - Drug: Matching placebo **Label:** Dosing regimen 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Intervention Names:** - Other: Celecoxib - Drug: Matching placebo **Label:** Dosing regimen 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Intervention Names:** - Drug: Matching placebo **Label:** Dosing regimen 4 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dosing regimen 1 **Description:** Solution for injection in pre-filled syringe **Name:** Fasinumab **Other Names:** - REGN475 - MT-5547 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Dosing regimen 2 **Description:** NSAID active comparator (capsule) **Name:** Diclofenac **Other Names:** - ZORVOLEX **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Dosing regimen 3 **Description:** NSAID active comparator (capsule) **Name:** Celecoxib **Other Names:** - CELEBREX **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Dosing regimen 1 - Dosing regimen 2 - Dosing regimen 3 - Dosing regimen 4 **Description:** Fasinumab-matching placebo (solution for injection in pre-filled syringe); NSAID-matching placebo (capsule) **Name:** Matching placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain. **Measure:** Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo **Time Frame:** Baseline up to Week 24 **Description:** Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty. **Measure:** Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo **Time Frame:** Baseline up to Week 24 #### Secondary Outcomes **Description:** WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a NRS of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. **Measure:** Percentage of Participants With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Participants Treated With Fasinumab Compared to Placebo **Time Frame:** Baseline up to Week 24 **Description:** The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition. **Measure:** Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo **Time Frame:** Baseline up to Week 24 **Description:** WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain. **Measure:** Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs **Time Frame:** Baseline up to Week 24 **Description:** Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty. **Measure:** Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs **Time Frame:** Baseline up to Week 24 **Description:** The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition. **Measure:** Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs **Time Frame:** Baseline up to Week 24 **Description:** Participants reported weekly average walking index joint pain based on NRS. The NRS was nationally recognized numeric scale from 0 to 10, where 0 would demonstrate no pain, 1 to 3 would demonstrate mild pain, 4 to 6 would be moderate pain, 7 to 9 would be severe pain and 10 would be the worst pain possible. Higher score indicated greater pain. **Measure:** Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale **Time Frame:** Baseline up to Week 24 **Description:** AA was a composite term that encompasses the following conditions: Rapidly progressive Osteoarthritis (OA) type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee. AAs were also evaluated to determine if they met Destructive Arthropathy criteria. **Measure:** Number of Participants With Adjudicated Arthropathy (AA) Events **Time Frame:** Baseline up to follow-up period (Week 44) **Description:** DA is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee. **Measure:** Number of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria **Time Frame:** Baseline up to follow-up period (Week 44) **Description:** An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. TEAE was defined as an AE with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs. **Measure:** Number of Participants With Treatment Emergent Adverse Events (TEAEs) **Time Frame:** Baseline up to follow-up period (Week 44) **Description:** Potential events of SNS dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist. **Measure:** Number of Participants With Sympathetic Nervous System (SNS) Dysfunction Events **Time Frame:** Baseline up to follow-up period (Week 44) **Description:** Any participants with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an Adverse Events of Special Interest (AESI). **Measure:** Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs) **Time Frame:** Baseline up to Week 44 **Description:** Number of participants who underwent a JR surgery from baseline up to Week 24 were reported. **Measure:** Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24 **Time Frame:** Baseline up to Week 24 **Description:** Number of participants who underwent a JR surgery from baseline up to follow-up period (Week 44) were reported. **Measure:** Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44 **Time Frame:** Baseline up to Week 44 **Description:** An EOS phone contact was conducted at Week 72 following the last dose of study drug (Week 24) to evaluate the number of participants who had undergone or were scheduled for JR surgery. **Measure:** Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72) **Time Frame:** At Week 72 **Measure:** Serum Concentrations of Functional Fasinumab **Time Frame:** At Weeks 0, 4, 8, 16, 24 and 44 **Description:** Immunogenicity was characterized by ADA responses \& titers. Responses categories: Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses \< 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, \>= 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response post first dose when baseline results = negative or missing. **Measure:** Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development **Time Frame:** Baseline up to Week 44 ### Eligibility Module **Eligibility Criteria:** Key Inclusion Criteria (additional criteria may apply at screening): 1. A clinical diagnosis of osteoarthritis (OA) of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2 for the index joint) at the screening visit. 2. Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments (acetaminophen/paracetamol to be taken as needed with a maximum daily dose of 2500 mg \[countries where 500 mg strength tablets/capsules are available\] or 2600 mg \[countries where 325 mg strength tablets/capsules are available\]) 3. A history of at least 12 weeks of inadequate pain relief or intolerance to analgesics used for pain due to OA of the knee or hip 4. Currently using a stable dose of NSAID 5. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the 24 weeks of treatment Key Exclusion Criteria (additional criteria may apply at screening): 1. Non-compliance with the numeric rating scale (NRS) recording during the pre-randomization period 2. History or presence at the screening visit of non-OA inflammatory joint disease, Paget's disease of the spine, pelvis or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy 3. History or presence on imaging of arthropathy, hip or knee dislocation, extensive subchondral cysts, evidence of severe structural damage, bone collapse, or primary metastatic tumor with the exception of chondromas or pathologic fractures 4. Trauma to the index joint within 3 months prior to the screening visit 5. Signs or symptoms of carpal tunnel syndrome within 6 months of screening 6. Patient is not a candidate for magnetic resonance imaging (MRI) 7. Is scheduled for a JR surgery to be performed during the study period or who would be unwilling or unable to undergo JR surgery if needed 8. History or presence at the screening visit of autonomic or diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy 9. Evidence of autonomic neuropathy as defined in the schedule of assessments (SoAs) 10. History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy 11. Use of systemic corticosteroids within 30 days prior to the screening visit. Intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit, or to any other joint within 30 days prior to the screening visit 12. Exposure to an anti-NGF antibody prior to the screening visit or known sensitivity or intolerance to anti-NGF antibodies 13. Women of childbearing potential who are unwilling to practice highly effective contraception prior to the start of the first treatment, during the study, and for at least 20 weeks after the last dose **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Anniston **Country:** United States **Facility:** Pinnacle Research Group, Llc **State:** Alabama **Zip:** 36207 **Location 2:** **City:** Mobile **Country:** United States **Facility:** Horizon Research Partners **State:** Alabama **Zip:** 36608 **Location 3:** **City:** Chandler **Country:** United States **Facility:** Clinical Research Advantage, Inc./Warner Family Practice, PC **State:** Arizona **Zip:** 85224 **Location 4:** **City:** Phoenix **Country:** United States **Facility:** Synexus Central Phoenix Medical Clinic **State:** Arizona **Zip:** 85020 **Location 5:** **City:** Tempe **Country:** United States **Facility:** Clinical Research Consortium Arizona **State:** Arizona **Zip:** 85283 **Location 6:** **City:** Anaheim **Country:** United States **Facility:** Advance Research Center **State:** California **Zip:** 92805 **Location 7:** **City:** El Cajon **Country:** United States **Facility:** TriWest Research Associates, LLC **State:** California **Zip:** 92020 **Location 8:** **City:** Garden Grove **Country:** United States **Facility:** Paragon Rx Clinical Research, Inc. **State:** California **Zip:** 92840 **Location 9:** **City:** Montclair **Country:** United States **Facility:** Catalina Research Institute, LLC **State:** California **Zip:** 91763 **Location 10:** **City:** Roseville **Country:** United States **Facility:** Sierra Clinical Research **State:** California **Zip:** 95661 **Location 11:** **City:** Sacramento **Country:** United States **Facility:** UC Davis Center for Musculoskeletal Health **State:** California **Zip:** 95817 **Location 12:** **City:** San Diego **Country:** United States **Facility:** Advanced Research Center, Inc **State:** California **Zip:** 92103 **Location 13:** **City:** San Diego **Country:** United States **Facility:** California Research Foundation **State:** California **Zip:** 92123 **Location 14:** **City:** Santa Ana **Country:** United States **Facility:** Paragon Rx Clinical Research, Inc **State:** California **Zip:** 92703 **Location 15:** **City:** Spring Valley **Country:** United States **Facility:** Encompass Clinical Research **State:** California **Zip:** 91978 **Location 16:** **City:** Thousand Oaks **Country:** United States **Facility:** Westlake Medical Research **State:** California **Zip:** 91360 **Location 17:** **City:** Vista **Country:** United States **Facility:** Synexus Clinical Research US, Inc. **State:** California **Zip:** 92083 **Location 18:** **City:** Denver **Country:** United States **Facility:** Mountain View Clinical Research **State:** Colorado **Zip:** 80209 **Location 19:** **City:** Bridgeport **Country:** United States **Facility:** New England Research Associates, LLC **State:** Connecticut **Zip:** 06606 **Location 20:** **City:** Hamden **Country:** United States **Facility:** CRM of Greater New Haven, LLC **State:** Connecticut **Zip:** 06157 **Location 21:** **City:** Stamford **Country:** United States **Facility:** Stamford Therapeutics Consortium **State:** Connecticut **Zip:** 06905 **Location 22:** **City:** DeLand **Country:** United States **Facility:** Avail Clinical Research, LLC **State:** Florida **Zip:** 32720 **Location 23:** **City:** Miami Lakes **Country:** United States **Facility:** Lakes Research, LLC **State:** Florida **Zip:** 33014 **Location 24:** **City:** Miami **Country:** United States **Facility:** AMB Research Center, Inc **State:** Florida **Zip:** 33144 **Location 25:** **City:** Miami **Country:** United States **Facility:** Allied Biomedical Research Institute **State:** Florida **Zip:** 33155 **Location 26:** **City:** Orlando **Country:** United States **Facility:** Bioclinica Research **State:** Florida **Zip:** 32806 **Location 27:** **City:** Pensacola **Country:** United States **Facility:** Gulf Region Clinical Research institute **State:** Florida **Zip:** 32514 **Location 28:** **City:** Plantation **Country:** United States **Facility:** Integral Rheumatology & Immunology Specialists (IRIS) **State:** Florida **Zip:** 33324 **Location 29:** **City:** Port Orange **Country:** United States **Facility:** Progressive Medical Research **State:** Florida **Zip:** 32127 **Location 30:** **City:** Marietta **Country:** United States **Facility:** Drug Studies America **State:** Georgia **Zip:** 30060 **Location 31:** **City:** Marietta **Country:** United States **Facility:** Georgia Institute For Clinical Research LLC **State:** Georgia **Zip:** 30060 **Location 32:** **City:** Woodstock **Country:** United States **Facility:** North Georgia Clinical Research **State:** Georgia **Zip:** 30189 **Location 33:** **City:** Chicago **Country:** United States **Facility:** Chicago Clinical Research Institute, Inc **State:** Illinois **Zip:** 60607 **Location 34:** **City:** Oak Lawn **Country:** United States **Facility:** Affinity Clinical Research Institute **State:** Illinois **Zip:** 60453 **Location 35:** **City:** Evansville **Country:** United States **Facility:** Clinical Research Advantage, Inc. **State:** Indiana **Zip:** 47714 **Location 36:** **City:** Evansville **Country:** United States **Facility:** MediSphere Medical Research Center, LLC **State:** Indiana **Zip:** 47714 **Location 37:** **City:** Louisville **Country:** United States **Facility:** L-MARC Research Center **State:** Kentucky **Zip:** 40213 **Location 38:** **City:** Marrero **Country:** United States **Facility:** Tandem Clinical Research **State:** Louisiana **Zip:** 70072 **Location 39:** **City:** Boston **Country:** United States **Facility:** Tufts Medical Center, Inc. **State:** Massachusetts **Zip:** 02111 **Location 40:** **City:** Bay City **Country:** United States **Facility:** Great Lakes Research Group, Inc. **State:** Michigan **Zip:** 48706 **Location 41:** **City:** Caro **Country:** United States **Facility:** Onyx Clinical Research **State:** Michigan **Zip:** 48723 **Location 42:** **City:** Richfield **Country:** United States **Facility:** Synexus Clinical Research US, Inc. **State:** Minnesota **Zip:** 55423 **Location 43:** **City:** Elkhorn **Country:** United States **Facility:** Skyline Medical Center /Radiant Research, Inc. **State:** Nebraska **Zip:** 68022 **Location 44:** **City:** Omaha **Country:** United States **Facility:** Meridian Clinical Research Associates, LLC **State:** Nebraska **Zip:** 68134 **Location 45:** **City:** Las Vegas **Country:** United States **Facility:** Robert Kaplan, D.O. **State:** Nevada **Zip:** 89144 **Location 46:** **City:** Raritan **Country:** United States **Facility:** Amici Clinical Research, LLC **State:** New Jersey **Zip:** 08869 **Location 47:** **City:** Albuquerque **Country:** United States **Facility:** Albuquerque Clinical Trials, Inc. **State:** New Mexico **Zip:** 87102 **Location 48:** **City:** Brooklyn **Country:** United States **Facility:** Drug Trial Brooklyn **State:** New York **Zip:** 11230 **Location 49:** **City:** Great Neck **Country:** United States **Facility:** Northwell Health **State:** New York **Zip:** 11021 **Location 50:** **City:** Hartsdale **Country:** United States **Facility:** Drug Trials America **State:** New York **Zip:** 10530 **Location 51:** **City:** Williamsville **Country:** United States **Facility:** Upstate Clinical Research Associates, LLC **State:** New York **Zip:** 14221 **Location 52:** **City:** Shelby **Country:** United States **Facility:** Carolina Research Center **State:** North Carolina **Zip:** 28150 **Location 53:** **City:** Wilmington **Country:** United States **Facility:** PMG Research of Wilmington LLC **State:** North Carolina **Zip:** 28401 **Location 54:** **City:** Winston-Salem **Country:** United States **Facility:** The Center For Clinical Research **State:** North Carolina **Zip:** 27103 **Location 55:** **City:** Cincinnati **Country:** United States **Facility:** New Horizons Clinical Research **State:** Ohio **Zip:** 45242 **Location 56:** **City:** Columbus **Country:** United States **Facility:** Aventiv Research Inc **State:** Ohio **Zip:** 43213 **Location 57:** **City:** Dayton **Country:** United States **Facility:** DOC Clinical Research **State:** Ohio **Zip:** 45432 **Location 58:** **City:** Indiana **Country:** United States **Facility:** Center for Orthopaedics and Sports Medicine **State:** Pennsylvania **Zip:** 15701 **Location 59:** **City:** Anderson **Country:** United States **Facility:** Radiant Research, Inc. **State:** South Carolina **Zip:** 29621 **Location 60:** **City:** Greenville **Country:** United States **Facility:** Piedmont Comprehensive Pain Management Group **State:** South Carolina **Zip:** 29601 **Location 61:** **City:** Greer **Country:** United States **Facility:** Radiant Research, Inc. **State:** South Carolina **Zip:** 29651 **Location 62:** **City:** Indian Land **Country:** United States **Facility:** Piedmont Research Partners, LLC **State:** South Carolina **Zip:** 29707 **Location 63:** **City:** North Charleston **Country:** United States **Facility:** Coastal Carolina Research Center at LowCountry Orthopaedics **State:** South Carolina **Zip:** 29406 **Location 64:** **City:** Orangeburg **Country:** United States **Facility:** ACME Research, LLC **State:** South Carolina **Zip:** 29118 **Location 65:** **City:** Memphis **Country:** United States **Facility:** Office of Dr.Ramesh C. Gupta MD **State:** Tennessee **Zip:** 38119 **Location 66:** **City:** Lubbock **Country:** United States **Facility:** West Texas Clinical Research **State:** Texas **Zip:** 79410 **Location 67:** **City:** Plano **Country:** United States **Facility:** Clinical Investigations Of Texas **State:** Texas **Zip:** 75075 **Location 68:** **City:** Plano **Country:** United States **Facility:** Synexus USA **State:** Texas **Zip:** 75093 **Location 69:** **City:** Charlottesville **Country:** United States **Facility:** Charlottesville Medical Research Center LLC **State:** Virginia **Zip:** 22911 **Location 70:** **City:** Newport News **Country:** United States **Facility:** Health Research of Hampton Roads, Inc **State:** Virginia **Zip:** 23606 **Location 71:** **City:** Spokane **Country:** United States **Facility:** Spokane Joint Replacement Center **State:** Washington **Zip:** 99218 #### Overall Officials **Official 1:** **Affiliation:** Regeneron Pharmaceuticals **Name:** Clinical Trial Management **Role:** STUDY_DIRECTOR ## Document Section ### Large Document Module #### Large Docs - Date: 2018-07-11 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1024724 - Type Abbrev: Prot - Upload Date: 2022-12-09T14:25 - Date: 2020-04-16 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 716112 - Type Abbrev: SAP - Upload Date: 2022-12-09T14:25 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M12926 - Name: Osteoarthritis - Relevance: HIGH - As Found: Osteoarthritis - ID: M22168 - Name: Osteoarthritis, Knee - Relevance: HIGH - As Found: Osteoarthritis, Knee - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M17912 - Name: Osteoarthritis, Hip - Relevance: HIGH - As Found: Osteoarthritis, Hip - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010003 - Term: Osteoarthritis - ID: D000020370 - Term: Osteoarthritis, Knee - ID: D000015207 - Term: Osteoarthritis, Hip ### Intervention Browse Module - Ancestors - ID: D000000894 - Term: Anti-Inflammatory Agents, Non-Steroidal - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000018501 - Term: Antirheumatic Agents - ID: D000052246 - Term: Cyclooxygenase 2 Inhibitors - ID: D000016861 - Term: Cyclooxygenase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M7197 - Name: Diclofenac - Relevance: HIGH - As Found: Personalized - ID: M277 - Name: Celecoxib - Relevance: HIGH - As Found: Air - ID: M4218 - Name: Anti-Inflammatory Agents, Non-Steroidal - Relevance: LOW - As Found: Unknown - ID: M293679 - Name: Fasinumab - Relevance: HIGH - As Found: Exercise habits - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M27009 - Name: Cyclooxygenase 2 Inhibitors - Relevance: LOW - As Found: Unknown - ID: M19209 - Name: Cyclooxygenase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068579 - Term: Celecoxib - ID: D000004008 - Term: Diclofenac - ID: C000626997 - Term: Fasinumab ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2023-01-06 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Placebo **Deaths Num Affected:** 1 **Deaths Num At Risk:** 309 **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** EG000 **Other Num Affected:** 121 **Other Num at Risk:** 309 **Serious Number Affected:** 20 **Serious Number At Risk:** 309 **Title:** Placebo **Group ID:** EG001 **Title:** NSAIDs **Deaths Num Affected:** 3 **Deaths Num At Risk:** 609 **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** EG001 **Other Num Affected:** 263 **Other Num at Risk:** 609 **Serious Number Affected:** 45 **Serious Number At Risk:** 609 **Title:** NSAIDs **Group ID:** EG002 **Title:** Fasinumab 1mg Q4W **Deaths Num Affected:** 1 **Deaths Num At Risk:** 609 **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** EG002 **Other Num Affected:** 261 **Other Num at Risk:** 609 **Serious Number Affected:** 35 **Serious Number At Risk:** 609 **Title:** Fasinumab 1mg Q4W **Group ID:** EG003 **Title:** Fasinumab 3mg Q4W **Deaths Num At Risk:** 58 **Description:** Participants received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** EG003 **Other Num Affected:** 17 **Other Num at Risk:** 58 **Serious Number Affected:** 5 **Serious Number At Risk:** 58 **Title:** Fasinumab 3mg Q4W **Group ID:** EG004 **Title:** Fasinumab 6mg Q8W **Deaths Num At Risk:** 59 **Description:** Participants received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Participants received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID **ID:** EG004 **Other Num Affected:** 15 **Other Num at Risk:** 59 **Serious Number Affected:** 2 **Serious Number At Risk:** 59 **Title:** Fasinumab 6mg Q8W **Frequency Threshold:** 5 #### Other Events **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.1) **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) **Term:** Blood creatine phosphokinase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.1) **Term:** Ligament sprain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) **Term:** Muscle strain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) #### Serious Events **Term:** Arteriosclerosis coronary artery **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Atrial fibrillation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 609 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Cardiac failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Vertigo positional **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Retinal detachment **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Gastritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Gastrointestinal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 609 **Num Events:** 2 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Hiatus hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Pancreatitis acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Cholecystitis acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 609 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Peritonsillar abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Wound infection staphylococcal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Concussion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Femur fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Fractured sacrum **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Multiple injuries **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Radius fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Hyperkalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Hyponatraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 2 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Intervertebral disc protrusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 309 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 609 **Num Events:** 6 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Osteoporotic fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Rapidly progressive osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 309 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 8 **Num At Risk:** 609 **Num Events:** 9 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 58 **Num Events:** 2 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 59 **Num Events:** 2 **Term:** Rotator cuff syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 609 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Spinal synovial cyst **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Tendonitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Prostate cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 609 **Num Events:** 2 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Amnesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Cerebrovascular accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 609 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Presyncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Trigeminal neuralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Device loosening **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Product Issues **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Endometrial hyperplasia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Uterine prolapse **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Pulmonary embolism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Joint arthroplasty **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 609 **Num Events:** 3 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Knee arthroplasty **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 609 **Num Events:** 4 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 609 **Num Events:** 3 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Arteriosclerosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Hypertensive crisis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Varicose vein **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Acute myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Atrioventricular block complete **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Cardiac arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Diverticulum intestinal haemorrhagic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Large intestine polyp **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Rectal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Impaired healing **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Cholelithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Atypical pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** COVID-19 pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Influenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Lower respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Meningitis viral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Accidental overdose **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Hip fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Tendon injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Tendon rupture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Arthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Bursitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Joint range of motion decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Lumbar spinal stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Spinal osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Spinal stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Subchondral insufficiency fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 58 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Invasive papillary breast carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Pseudostroke **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Device dislocation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Product Issues **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Depressed mood **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Nephrolithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num At Risk:** 609 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Breast cyst **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Hip arthroplasty **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 309 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 609 **Num Events:** 3 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 309 **Group ID:** EG001 **Num At Risk:** 609 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 609 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 58 **Group ID:** EG004 **Num At Risk:** 59 **Time Frame:** First dose to week 44 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 308 **Group ID:** BG001 **Value:** 612 **Group ID:** BG002 **Value:** 612 **Group ID:** BG003 **Value:** 59 **Group ID:** BG004 **Value:** 59 **Group ID:** BG005 **Value:** 1650 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. ### Group **ID:** BG001 **Title:** NSAIDs **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. ### Group **ID:** BG002 **Title:** Fasinumab 1 mg **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID ### Group **ID:** BG003 **Title:** Fasinumab 3 mg **Description:** Participants received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID ### Group **ID:** BG004 **Title:** Fasinumab 6 mg **Description:** Participants received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Participants received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID ### Group **ID:** BG005 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.30 **Value:** 62.0 #### Measurement **Group ID:** BG001 **Spread:** 9.41 **Value:** 62.3 #### Measurement **Group ID:** BG002 **Spread:** 9.13 **Value:** 62.1 #### Measurement **Group ID:** BG003 **Spread:** 9.38 **Value:** 62.8 #### Measurement **Group ID:** BG004 **Spread:** 9.55 **Value:** 61.5 #### Measurement **Group ID:** BG005 **Spread:** 9.28 **Value:** 62.2 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 308 **Group ID:** BG001 **Value:** 612 **Group ID:** BG002 **Value:** 612 **Group ID:** BG003 **Value:** 59 **Group ID:** BG004 **Value:** 59 **Group ID:** BG005 **Value:** 1650 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 222 #### Measurement **Group ID:** BG001 **Value:** 418 #### Measurement **Group ID:** BG002 **Value:** 436 #### Measurement **Group ID:** BG003 **Value:** 36 #### Measurement **Group ID:** BG004 **Value:** 34 #### Measurement **Group ID:** BG005 **Value:** 1146 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 86 #### Measurement **Group ID:** BG001 **Value:** 194 #### Measurement **Group ID:** BG002 **Value:** 176 #### Measurement **Group ID:** BG003 **Value:** 23 #### Measurement **Group ID:** BG004 **Value:** 25 #### Measurement **Group ID:** BG005 **Value:** 504 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 308 **Group ID:** BG001 **Value:** 612 **Group ID:** BG002 **Value:** 612 **Group ID:** BG003 **Value:** 59 **Group ID:** BG004 **Value:** 59 **Group ID:** BG005 **Value:** 1650 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 20 #### Measurement **Group ID:** BG001 **Value:** 44 #### Measurement **Group ID:** BG002 **Value:** 31 #### Measurement **Group ID:** BG003 **Value:** 5 #### Measurement **Group ID:** BG004 **Value:** 10 #### Measurement **Group ID:** BG005 **Value:** 110 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 285 #### Measurement **Group ID:** BG001 **Value:** 568 #### Measurement **Group ID:** BG002 **Value:** 581 #### Measurement **Group ID:** BG003 **Value:** 54 #### Measurement **Group ID:** BG004 **Value:** 49 #### Measurement **Group ID:** BG005 **Value:** 1537 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 3 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 308 **Group ID:** BG001 **Value:** 612 **Group ID:** BG002 **Value:** 612 **Group ID:** BG003 **Value:** 59 **Group ID:** BG004 **Value:** 59 **Group ID:** BG005 **Value:** 1650 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 2 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 33 #### Measurement **Group ID:** BG001 **Value:** 57 #### Measurement **Group ID:** BG002 **Value:** 54 #### Measurement **Group ID:** BG003 **Value:** 8 #### Measurement **Group ID:** BG004 **Value:** 3 #### Measurement **Group ID:** BG005 **Value:** 155 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 2 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 60 #### Measurement **Group ID:** BG001 **Value:** 134 #### Measurement **Group ID:** BG002 **Value:** 132 #### Measurement **Group ID:** BG003 **Value:** 12 #### Measurement **Group ID:** BG004 **Value:** 16 #### Measurement **Group ID:** BG005 **Value:** 354 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 202 #### Measurement **Group ID:** BG001 **Value:** 396 #### Measurement **Group ID:** BG002 **Value:** 405 #### Measurement **Group ID:** BG003 **Value:** 39 #### Measurement **Group ID:** BG004 **Value:** 40 #### Measurement **Group ID:** BG005 **Value:** 1082 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 24 #### Measurement **Group ID:** BG002 **Value:** 18 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 53 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 2 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 308 **Group ID:** BG001 **Value:** 612 **Group ID:** BG002 **Value:** 612 **Group ID:** BG003 **Value:** 59 **Group ID:** BG004 **Value:** 59 **Group ID:** BG005 **Value:** 1650 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.394 **Value:** 6.42 #### Measurement **Group ID:** BG001 **Spread:** 1.344 **Value:** 6.38 #### Measurement **Group ID:** BG002 **Spread:** 1.321 **Value:** 6.46 #### Measurement **Group ID:** BG003 **Spread:** 1.401 **Value:** 6.43 #### Measurement **Group ID:** BG004 **Spread:** 1.279 **Value:** 6.54 #### Measurement **Group ID:** BG005 **Spread:** 1.344 **Value:** 6.42 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 308 **Group ID:** BG001 **Value:** 611 **Group ID:** BG002 **Value:** 612 **Group ID:** BG003 **Value:** 58 **Group ID:** BG004 **Value:** 59 **Group ID:** BG005 **Value:** 1648 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.495 **Value:** 6.40 #### Measurement **Group ID:** BG001 **Spread:** 1.418 **Value:** 6.32 #### Measurement **Group ID:** BG002 **Spread:** 1.462 **Value:** 6.39 #### Measurement **Group ID:** BG003 **Spread:** 1.350 **Value:** 6.50 #### Measurement **Group ID:** BG004 **Spread:** 1.392 **Value:** 6.34 #### Measurement **Group ID:** BG005 **Spread:** 1.445 **Value:** 6.37 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 304 **Group ID:** BG001 **Value:** 609 **Group ID:** BG002 **Value:** 610 **Group ID:** BG003 **Value:** 58 **Group ID:** BG004 **Value:** 57 **Group ID:** BG005 **Value:** 1638 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Description:** WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Here 'n' = number of evaluable participants at the specified time point **Title:** Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score **Unit of Measure:** Score on a scale ### Measure 6 **Description:** WOMAC physical function subscale:17-item questionnaire used to assess degree of difficulty experienced due to OA in index joint during past 48 hours. It was calculated as mean of scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Here 'n' = number of evaluable participants at the specified time point **Title:** WOMAC Physical Function Subscale Scores **Unit of Measure:** Score on a scale ## Results Section - More Information Module ### Certain Agreement **Other Details:** The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Regeneron Pharmaceuticals, Inc. **Phone:** 844-734-6643 **Title:** Clinical Trials Administrator ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -0.971 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.286 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Analyses were based on a multiple imputation approach using a Mixed-Effect Model With Repeated Measure (MMRM) model with baseline randomization strata, baseline, treatment, visit and treatment by-visit interaction. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** = 0.0003 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Least Square (LS) Mean Difference **Parameter Value:** -0.63 **Statistical Comment:** **Statistical Method:** MMRM **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -1.154 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.383 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** (mFAS) Analyses were based on a multiple imputation approach using a MMRM model with baseline, randomization strata, baseline, treatment, visit and treatment by-visit interaction **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** > 0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -0.77 **Statistical Comment:** **Statistical Method:** MMRM **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -0.981 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.290 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Analyses were based on a multiple imputation approach using a Mixed-Effect Model With Repeated Measure (MMRM) model with baseline randomization strata, baseline, treatment, visit and treatment by-visit interaction. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** = 0.0003 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -0.64 **Statistical Comment:** **Statistical Method:** MMRM **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -1.198 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.443 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** (mFAS) Analyses were based on a multiple imputation approach using an Mixed-Effect Model With Repeated Measure (MMRM) model with baseline randomization strata, baseline, treatment, visit and treatment by-visit interaction. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level **Parameter Type:** LS Mean Difference **Parameter Value:** -0.82 **Statistical Comment:** **Statistical Method:** MMRM **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 1.195 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.092 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. Analyses are based on Cochran-Mantel-Haenszel model. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** = 0.0013 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.581 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -0.28 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.009 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. Analyses are based on a multiple imputation approach using Mixed-Effect Model With Repeated Measure (MMRM) model. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** = 0.0365 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -0.14 **Statistical Comment:** **Statistical Method:** MMRM **Tested Non-Inferiority:** ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ### Outcome Measure 17 ### Outcome Measure 18 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.165 - **Upper Limit:** - **Value:** -2.21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.127 - **Upper Limit:** - **Value:** -2.84 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 208 - **Group ID:** OG001 - **Value:** 439 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.182 - **Upper Limit:** - **Value:** -2.01 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.141 - **Upper Limit:** - **Value:** -2.78 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 173 - **Group ID:** OG001 - **Value:** 372 **Units:** Participants #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.164 - **Upper Limit:** - **Value:** -2.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.125 - **Upper Limit:** - **Value:** -2.65 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 207 - **Group ID:** OG001 - **Value:** 439 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.180 - **Upper Limit:** - **Value:** -1.80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.138 - **Upper Limit:** - **Value:** -2.62 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 172 - **Group ID:** OG001 - **Value:** 372 **Units:** Participants #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 48.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 59.8 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.063 - **Upper Limit:** - **Value:** -0.66 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.047 - **Upper Limit:** - **Value:** -0.81 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.128 - **Upper Limit:** - **Value:** -2.60 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.127 - **Upper Limit:** - **Value:** -2.84 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 426 - **Group ID:** OG001 - **Value:** 439 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.140 - **Upper Limit:** - **Value:** -2.48 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.141 - **Upper Limit:** - **Value:** -2.78 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 363 - **Group ID:** OG001 - **Value:** 372 **Units:** Participants #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.127 - **Upper Limit:** - **Value:** -2.33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.125 - **Upper Limit:** - **Value:** -2.65 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 426 - **Group ID:** OG001 - **Value:** 439 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.140 - **Upper Limit:** - **Value:** -2.26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.138 - **Upper Limit:** - **Value:** -2.62 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 364 - **Group ID:** OG001 - **Value:** 372 **Units:** Participants #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.048 - **Upper Limit:** - **Value:** -0.75 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.047 - **Upper Limit:** - **Value:** -0.81 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.130 - **Upper Limit:** - **Value:** -1.85 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.101 - **Upper Limit:** - **Value:** -2.13 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.100 - **Upper Limit:** - **Value:** -2.51 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 34 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 186 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 406 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 403 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.002 - **Upper Limit:** - **Value:** 0.000155 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 586 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0179 - **Upper Limit:** - **Value:** 0.0469 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 570 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0275 - **Upper Limit:** - **Value:** 0.0644 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 543 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0380 - **Upper Limit:** - **Value:** 0.0738 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 502 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0379 - **Upper Limit:** - **Value:** 0.0713 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 465 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.00476 - **Upper Limit:** - **Value:** 0.000349 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 186 **Units:** Participants #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** This outcome measure examined only placebo vs. fasinumab 1mg arms. Here, "Number of Subjects Analysed" signifies those subjects who were evaluable for this endpoint. Modified full analysis set (mFAS) includes all randomized participants in FAS but excludes participants from 4 sites for which there were potential concerns regarding data quality, identified prior to database lock. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo **Type:** PRIMARY **Unit of Measure:** Score on a Scale ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG001 **Title:** Fasinumab 1 mg #### Outcome Measure 2 **Description:** Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** This outcome measure examined only placebo vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized participants in the FAS but excludes participants from four sites for which there were potential concerns regarding data quality, identified prior to database lock. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo **Type:** PRIMARY **Unit of Measure:** Score on a Scale ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG001 **Title:** Fasinumab 1 mg #### Outcome Measure 3 **Description:** WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a NRS of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. **Parameter Type:** NUMBER **Population Description:** The FAS included all randomized participants excluding participants affected by the urgent safety measure and was based on the treatment allocated (as randomized). As pre-specified in the protocol, efficacy data from participants randomized to Fasinumab 1 mg Q4W and placebo was only included in the analysis for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Percentage of Participants With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Participants Treated With Fasinumab Compared to Placebo **Type:** SECONDARY **Unit of Measure:** Percentage of Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG001 **Title:** Fasinumab 1 mg #### Outcome Measure 4 **Description:** The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** This outcome measure examined only placebo vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo **Type:** SECONDARY **Unit of Measure:** Score on a Scale ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG001 **Title:** Fasinumab 1 mg #### Outcome Measure 5 **Description:** WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** This outcome measure examined only NSAIDs vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized participants in the FAS but excludes participants from four sites for which there were potential concerns regarding data quality, identified prior to database lock. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs **Type:** SECONDARY **Unit of Measure:** Score on a Scale ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG000 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG001 **Title:** Fasinumab 1 mg #### Outcome Measure 6 **Description:** Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** This outcome measure examined only NSAIDs vs. fasinumab 1mg arms. Here, "Number of Subjects Analysed" signifies those subjects who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized participants in the FAS but excludes participants from four sites for which there were potential concerns regarding data quality, identified prior to database lock. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs **Type:** SECONDARY **Unit of Measure:** Score on a Scale ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG000 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG001 **Title:** Fasinumab 1 mg #### Outcome Measure 7 **Description:** The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** This outcome measure examined only NSAIDs vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs **Type:** SECONDARY **Unit of Measure:** Score on a Scale ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG000 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG001 **Title:** Fasinumab 1 mg #### Outcome Measure 8 **Description:** Participants reported weekly average walking index joint pain based on NRS. The NRS was nationally recognized numeric scale from 0 to 10, where 0 would demonstrate no pain, 1 to 3 would demonstrate mild pain, 4 to 6 would be moderate pain, 7 to 9 would be severe pain and 10 would be the worst pain possible. Higher score indicated greater pain. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale **Type:** SECONDARY **Unit of Measure:** Score on a Scale ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Pooled Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 9 **Description:** AA was a composite term that encompasses the following conditions: Rapidly progressive Osteoarthritis (OA) type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee. AAs were also evaluated to determine if they met Destructive Arthropathy criteria. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. Safety Analysis set (SAF) included all randomized participants from the FAS who received any study drug. It was based on the actual treatment received. **Reporting Status:** POSTED **Time Frame:** Baseline up to follow-up period (Week 44) **Title:** Number of Participants With Adjudicated Arthropathy (AA) Events **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Pooled Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 10 **Description:** DA is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It was based on the actual treatment received. Here, "Number of Participants Analyzed" signifies those participants who had positive AA. **Reporting Status:** POSTED **Time Frame:** Baseline up to follow-up period (Week 44) **Title:** Number of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Pooled Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 11 **Description:** An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. TEAE was defined as an AE with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It was based on the actual treatment received. **Reporting Status:** POSTED **Time Frame:** Baseline up to follow-up period (Week 44) **Title:** Number of Participants With Treatment Emergent Adverse Events (TEAEs) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Pooled Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 12 **Description:** Potential events of SNS dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It was based on the actual treatment received. **Reporting Status:** POSTED **Time Frame:** Baseline up to follow-up period (Week 44) **Title:** Number of Participants With Sympathetic Nervous System (SNS) Dysfunction Events **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Pooled Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 13 **Description:** Any participants with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an Adverse Events of Special Interest (AESI). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 44 **Title:** Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 14 **Description:** Number of participants who underwent a JR surgery from baseline up to Week 24 were reported. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 24 **Title:** Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 15 **Description:** Number of participants who underwent a JR surgery from baseline up to follow-up period (Week 44) were reported. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 44 **Title:** Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 16 **Description:** An EOS phone contact was conducted at Week 72 following the last dose of study drug (Week 24) to evaluate the number of participants who had undergone or were scheduled for JR surgery. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received. **Reporting Status:** POSTED **Time Frame:** At Week 72 **Title:** Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg #### Outcome Measure 17 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic (PK) analysis set included all treated participants who received any study drug and who had at least 1 non-missing drug concentration result following the first study dose. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome measure and "Number Analyzed" = participants who were evaluable at specified time points. Data was planned to be collected and analyzed for Fasinumab 1 mg Q4W arm only. **Reporting Status:** POSTED **Time Frame:** At Weeks 0, 4, 8, 16, 24 and 44 **Title:** Serum Concentrations of Functional Fasinumab **Type:** SECONDARY **Unit of Measure:** Milligrams per Liter (mg/L) ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG000 **Title:** Fasinumab 1 mg #### Outcome Measure 18 **Description:** Immunogenicity was characterized by ADA responses \& titers. Responses categories: Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses \< 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, \>= 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response post first dose when baseline results = negative or missing. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. The ADA analysis set included all participants who received any study drug and had at least 1 non-missing ADA result following the first dose of study drug. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 44 **Title:** Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** OG001 **Title:** NSAIDs ##### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** OG002 **Title:** Fasinumab 1 mg ### Participant Flow Module #### Group **Description:** Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks. **ID:** FG000 **Title:** Placebo #### Group **Description:** Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks. **ID:** FG001 **Title:** NSAIDs #### Group **Description:** Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** FG002 **Title:** Fasinumab 1 mg #### Group **Description:** Participants received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID **ID:** FG003 **Title:** Fasinumab 3 mg #### Group **Description:** Participants received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Participants received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID **ID:** FG004 **Title:** Fasinumab 6 mg #### Period **Title:** Overall Study ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 8 ###### Reason **Group ID:** FG001 **Number of Subjects:** 10 ###### Reason **Group ID:** FG002 **Number of Subjects:** 5 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 2 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 20 ###### Reason **Group ID:** FG002 **Number of Subjects:** 17 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 17 ###### Reason **Group ID:** FG001 **Number of Subjects:** 16 ###### Reason **Group ID:** FG002 **Number of Subjects:** 20 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 6 ###### Reason **Group ID:** FG001 **Number of Subjects:** 10 ###### Reason **Group ID:** FG002 **Number of Subjects:** 6 ###### Reason **Group ID:** FG003 **Number of Subjects:** 9 ###### Reason **Group ID:** FG004 **Number of Subjects:** 10 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 26 ###### Reason **Group ID:** FG001 **Number of Subjects:** 58 ###### Reason **Group ID:** FG002 **Number of Subjects:** 66 ###### Reason **Group ID:** FG003 **Number of Subjects:** 3 ###### Reason **Group ID:** FG004 **Number of Subjects:** 5 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 8 ###### Reason **Group ID:** FG001 **Number of Subjects:** 24 ###### Reason **Group ID:** FG002 **Number of Subjects:** 35 ###### Reason **Group ID:** FG003 **Number of Subjects:** 4 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ##### Withdraw **Type:** Other ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 308 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 612 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 612 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 59 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 59 ##### Milestone **Type:** Full Analysis Set (FAS) **Comment:** FAS included all randomized participants excluding participants affected by the urgent safety measure and was based on the treatment allocated (as randomized) ###### Achievement **Group ID:** FG000 **Number of Subjects:** 308 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 612 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 612 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ##### Milestone **Type:** Safety Analysis Set (SAF) **Comment:** SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received. ###### Achievement **Group ID:** FG000 **Number of Subjects:** 309 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 609 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 609 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ##### Milestone **Type:** Urgent Safety Measure Set (USMS) **Comment:** USMS included all participants randomized to Fasinumab 3 mg Q4W or 6 mg Q8W and was based on the treatment allocated (as randomized) ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 59 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 59 ##### Milestone **Type:** Completed Treatment ###### Achievement **Group ID:** FG000 **Number of Subjects:** 218 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 436 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 454 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 238 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 471 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 463 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 42 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 42 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 70 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 141 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 149 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 17 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 17 **Pre-Assignment Details:** In May 2018, the sponsor implemented an urgent safety measure to stop dosing for participants randomized to Fasinumab (6 mg and 3 mg), to prevent further randomization to these regimens across the Fasinumab program based on review of unblinded data in an ongoing study R475-PN-1523 (NCT02683239). Participants from Fasinumab 3 mg and 6 mg group were moved directly into the 20-week follow-up period. **Recruitment Details:** A total of 4531 participants were screened in this study. Out of which, 1650 participants were randomized to 1 of the following arms: Fasinumab (1 milligram \[mg\]), non-steroidal anti-inflammatory drug (NSAIDs), matched placebo, Fasinumab 3 and 6 mg. Screen failure was mostly due to inclusion criteria not met/exclusion criteria met. Eligible participants were randomized to receive placebo matched to Fasinumab/NSAIDs, NSAIDs (Diclofenac and Celecoxib) and Fasinumab 1 mg. **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT01745679 **Brief Title:** Pharmacological Study of High Doses of Ceftriaxone in Meningitidis **Official Title:** Therapeutic Monitoring of Ceftriaxone, Prescribed at High Doses, in the Treatment of Meningitis and Others Neurological Infections. #### Organization Study ID Info **ID:** RC12_0171 #### Organization **Class:** OTHER **Full Name:** Nantes University Hospital ### Status Module #### Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-10-05 **Type:** ESTIMATED **Last Update Submit Date:** 2016-10-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Start Date **Date:** 2012-12 **Status Verified Date:** 2016-10 #### Study First Post Date **Date:** 2012-12-10 **Type:** ESTIMATED **Study First Submit Date:** 2012-12-04 **Study First Submit QC Date:** 2012-12-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nantes University Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of the study is to describe the concentrations of Ceftriaxone at the steady state, in patients treated for meningitis, to determine pharmacokinetic parameters at high dose in this population. Additionally, we aimed to detect adverse effect, especially neurological trouble related to Ceftriaxone toxicity. **Detailed Description:** Day 0 : onset of treatment by Ceftriaxone, following usual therapeutic process (French Guideline) From Day 0 to Day 4 : inclusion, clinical and biological data collection, electroencephalogram at baseline. Two samples for ceftriaxone concentration monitoring : * Trough concentration of ceftriaxone at steady state * A random sample (population PK) At the end of ceftriaxone treatment : assessment of tolerance and efficacy of the treatment. ### Conditions Module **Conditions:** - Meningitis - Neurological Infections **Keywords:** - Ceftriaxone - Adverse drug effects - Therapeutic monitoring - Meningitis ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 198 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** ceftriaxone will be administered à high dose : \> or equal to 75mg/kg/day or 4 gr/day **Intervention Names:** - Drug: Ceftriaxone treatment **Label:** Ceftriaxone treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Ceftriaxone treatment **Description:** ceftriaxone will be administered à high dose : \> or equal to 75mg/kg/day or 4 gr/day **Name:** Ceftriaxone treatment **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** plasmatic concentration of ceftriaxone, measured at the steady state (after 48 hours of treatment at least). **Time Frame:** after at least 48 hours of ceftriaxone treatment #### Secondary Outcomes **Description:** Neurological troubles explored by electroencephalogram aiming to diagnose epileptic syndrome. **Measure:** Neurological troubles **Time Frame:** participants will be followed for the duration of ceftriaxone treatment, an expected average of two weeks **Description:** Time of return to apyrexia, health complications and lenght of hospital stay will be registered. **Measure:** clinical evolution **Time Frame:** participants will be followed for the duration of ceftriaxone treatment, an expected average of 2 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Hospitalized adults patients, * age equal or above 18 * Patients with Community or surgical acquired neurological infections, meningitis and others * Prescription of ceftriaxone \>75mg/kg/d or \>4g/d - * Subjects affiliated to French health insurance (social security) * Informed consent form signed Exclusion Criteria: - Patient under guardianship **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Nantes **Country:** France **Facility:** Nantes Universitary Hospital **State:** Loire Atlantique **Zip:** 44093 **Location 2:** **City:** Angers **Country:** France **Facility:** Angers Universitary Hospital **Zip:** 49933 **Location 3:** **City:** La Roche/Yon **Country:** France **Facility:** La Roche/Yon hospital **Zip:** 85925 **Location 4:** **City:** Poitiers **Country:** France **Facility:** Poitiers Universitary hospital **Zip:** 86021 **Location 5:** **City:** Rennes **Country:** France **Facility:** Rennes Universitary hospital **Zip:** 35033 **Location 6:** **City:** St Nazaire **Country:** France **Facility:** St Nazaire hospital **Zip:** 44600 **Location 7:** **City:** Tours **Country:** France **Facility:** Tours universitary hospital **Zip:** 37170 ### References Module #### References **Citation:** Gregoire M, Dailly E, Le Turnier P, Garot D, Guimard T, Bernard L, Tattevin P, Vandamme YM, Hoff J, Lemaitre F, Verdier MC, Deslandes G, Bellouard R, Sebille V, Chiffoleau A, Boutoille D, Navas D, Asseray N. High-Dose Ceftriaxone for Bacterial Meningitis and Optimization of Administration Scheme Based on Nomogram. Antimicrob Agents Chemother. 2019 Aug 23;63(9):e00634-19. doi: 10.1128/AAC.00634-19. Print 2019 Sep. **PMID:** 31235630 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000090862 - Term: Neuroinflammatory Diseases - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC25 - Name: Substance Related Disorders - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M30303 - Name: Drug-Related Side Effects and Adverse Reactions - Relevance: LOW - As Found: Unknown - ID: M11564 - Name: Meningitis - Relevance: HIGH - As Found: Meningitis - ID: M2803 - Name: Neuroinflammatory Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000008581 - Term: Meningitis ### Intervention Browse Module - Ancestors - ID: D000097911 - Term: Third Generation Cephalosporins - ID: D000097902 - Term: Beta Lactam Antibiotics - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M5693 - Name: Ceftriaxone - Relevance: HIGH - As Found: Antimicrobial - ID: M5760 - Name: Cephalosporins - Relevance: LOW - As Found: Unknown - ID: M3453 - Name: Third Generation Cephalosporins - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M10789 - Name: Lactams - Relevance: LOW - As Found: Unknown - ID: M25772 - Name: beta-Lactams - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M3444 - Name: Beta Lactam Antibiotics - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002443 - Term: Ceftriaxone ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05844579 **Acronym:** LIBERATION **Brief Title:** The ICU LIBERATION Study **Official Title:** ReLatIonship BEtween Implementation of Evidence-based and suppoRtive ICU cAre and ouTcomes of patIents With Acute respiratOry Distress syNdrome #### Organization Study ID Info **ID:** 2200115 #### Organization **Class:** OTHER **Full Name:** Japanese Society for Early Mobilization ### Status Module #### Completion Date **Date:** 2031-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-26 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-06-01 **Type:** ACTUAL **Status Verified Date:** 2023-04 #### Study First Post Date **Date:** 2023-05-06 **Type:** ACTUAL **Study First Submit Date:** 2023-04-02 **Study First Submit QC Date:** 2023-04-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Japanese Society for Early Mobilization #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Acute respiratory distress syndrome (ARDS) is a condition associated with hypoxemia due to noncardiogenic causes and results in high mortality. However, the epidemiology and treatment strategy for ARDS may have changed significantly due to the accumulation of a large body of knowledge, following the two-year pandemic of the novel coronavirus (SARS-CoV-2) of which the primary manifestation is ARDS. To improve the quality of ICU care that patients receive after admission to the ICU, a variety of academic societies, including the Japanese Society of Intensive Care Medicine and the Society of Critical Care Medicine, are currently developing evidence-based guidelines and consensus guidelines and statements regarding ABCDEF bundles, nutritional therapy, ICU diary. The ABCDEF bundle, nutritional therapy, and ICU diary have been developed and are being promoted for implementation in hospitals around the world. The implementation of evidence-based ICU care is strongly recommended, especially for patients with acute respiratory distress syndrome who frequently require ventilators to maintain their lives, because their patient outcomes are worse than those who were admitted to ICU with other causes. However, there is still little evidence on how the quality of ICU care (compliance rate) correlates with patient prognosis and outcomes, and there are currently no clear goals or indicators for the ICU care we should develop. This study aims to investigate the epidemiology and treatments given to the patients and evaluate the implementation of evidence-based ICU care and its association with the outcomes of patients with acute respiratory distress syndrome admitted to the ICU. The contents of mechanical ventilation settings, respiratory conditions, and the evidence-based ICU care, such as analgesia, sedation, rehabilitation, and nutrition, given to the patients will be collected in a daily basis. Aim 1: Epidemiology Aim 2: Treatments Aim 3: Evidence-based ICU care Aim 4: ARDS related Post Intensive Care Syndrome **Detailed Description:** Background: Acute respiratory distress syndrome (ARDS) is a condition associated with hypoxemia due to noncardiogenic causes with bilateral lung infiltrates on chest X-ray or CT imaging. 10% of all ICU admissions are ARDS patients, and the recent pandemic of the novel coronavirus has dramatically increased the number of ARDS patients in ICUs across the world. The international epidemiological study (2016) reported a mortality rate of 35-46% for ARDS, and this is very high mortality compared to other ICU diseases. Furthermore, ARDS survivors present with many functional impairments, including physical, cognitive, and psychiatric dysfunction (Post Intensive Care Syndrome, PICS), and their Activities of Daily Living (ADL) and Quality of Life (QOL) are impaired and many other functional impairments have been pointed out. Their inability to get their original life has attracted significant research attention and become a significantly important research topic. Many patients who are unable to return to work due to functional disability require nursing care, and there is concern about the increased burden on the patient, the family supporting the patient, and the social economy. Therefore, the development of effective strategies for patients with ARDS that take into account not only mortality but also functional prognosis is strongly needed. Recent studies have shown that lung-protective ventilation (low tidal volume and airway pressure control), neuromuscular blocking agents, prone position, noninvasive mechanical ventilators, and extracorporeal membrane oxygenation (ECMO) have improved outcomes, including mortality, in patients with ARDS. However, the mortality of patients with ARDS is still as high as 40%. In addition, the complete reintegration ratio of patients with ARDS after 1 year of hospital discharge reported in 2003 was only 50%, and recent reports have shown little progress in this aspect. Strategies to improve outcomes (mortality and functional prognosis) of ARDS patients by improving not only treatment but also the quality of ICU care have become a hot topic in recent years. The previous paper showed that excessive sedation and absolute bed rest for the purpose of ventilation control and rest during intubation in ARDS patients correlated with delirium, prolonged duration of ventilation, and even increased mortality. Therefore, attempts have been explored to improve outcomes for ARDS patients by systematically providing sedation, analgesia, rehabilitation, spontaneous breathing and awaking tests, and delirium management during ICU admission. These attempts, known as the ABCDEF bundle, have been actively recommended by a number of academic societies to be introduced in ICUs as an attempt to improve outcomes of patients with ARDS and promote their reintegration into society. (ABCDEF bundle: A (Assess, prevent, and manage pain), B (Both spontaneous awakening trials (SAT) and spontaneous breathing trials (SBT)), C (Choice of analgesia and sedation), D (Delirium: assess, prevent, and manage), E (Early mobility and exercise), F (Family engagement and empowerment)), and even ICU care such as nutritional therapy and ICU diaries have been shown to improve outcomes for ICU patients, including ARDS, and are strongly recommended. (In this study, this ICU care is referred to as evidence-based ICU care.) On the other hand, our research team has reported that the overall implementation rate of these evidence-based ICU care, ABCDEF bundles, nutritional therapy, and ICU diaries in ICU patients is quite low, and the rate is significantly lower in mechanically ventilated patients. The reason for the low implementation rates is thought to be that the ventilator is a major barrier. Although many articles have proposed evidence-based ICU care, there is little evidence as to which of these should be prioritized and which should be combined to maximize patient outcomes. The reason for this may be that there is a lack of evidence on which of these should be prioritized and which should be combined to maximize patient outcomes. Implementation of evidence-based ICU care requires many resources and effort, and it is difficult to implement all of them simultaneously. Therefore, the purpose of this international multicenter study is to investigate the current epidemiology and treatment strategy given to the patients with ARDS after the two-year pandemic of the novel coronavirus, clarify the actual implementation of ICU care for ARDS patients who require ventilators at high frequency, and evaluate how the implementation of evidence-based ICU care is associated with patient outcomes. Significance of the study This study has the potential to increase the generalizability of the results which will be obtained from all regions of the world, including Asia, Europe, North and South America, Oceania, and Africa. Therefore, the results will potentially contribute to improving patient treatment and outcomes in all regions of the world. Furthermore, the results obtained will provide a detailed picture of the current ICU care given to patients with ARDS in the ICU. The association/correlation analysis between its implementation and patient outcomes will identify the content of ICU care which can maximize improvement in outcomes for ARDS patients. As a result, this study will contribute to the development of ICU care guidelines and thereby improve the outcomes of patients with ARDS. The study will play a significant role in improving outcomes for patients with ARDS worldwide. In addition, the results of this study will serve as basement data for future interventional research. ### Conditions Module **Conditions:** - Acute Respiratory Distress Syndrome - Post Intensive Care Syndrome - Treatment Compliance - Quality of Life ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1000 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 3 Months ### Outcomes Module #### Primary Outcomes **Description:** For Aim 1 **Measure:** Mortality **Time Frame:** at the time of hospital discharge (an average of 20 days) **Description:** For Aim 2 **Measure:** Compliance of lung protective ventilation defined as Tidal Volme < 6ml/kg, Plateau Pressure < 30 cmH2O, and Driving Pressure < 15cmH2O that can be measured on the mechanical ventilator **Time Frame:** within the first two weeks of ICU admission **Description:** For Aim 3 **Measure:** The implementation rate of an entire and each component of the ABCDEF bundle **Time Frame:** within the first two weeks of ICU admission **Description:** For Aim 4: Post Intensive Care Syndrome defined as any of the following criteria; (1) physical impairment defined as the presence of Barthel Index 90 and less, (2) cognitive impairment defined as the presence of MMSE below 24 , or (3) mental health disorders defined as the presence of HADs Anxiety 8 or higher, HADs Depression 8 or higher, or IES-R 25 or higher **Measure:** Incidence of Post Intensive Care Syndrome **Time Frame:** at the time of follow-up 3 months after hospital discharge ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Patients on an invasive or non-invasive ventilator within 24 hours of ICU admission 2. Patients who are expected to be on an invasive and/or non-invasive ventilator for more than 48 hours in total 3. Patients who meet the diagnosis of ARDS within 24 hours of ICU admission Exclusion Criteria: 1. Patients who are younger than 16 years old 2. Patients with terminal conditions at the time of ICU admission 3. Patients who have been admitted to the ICU with a terminal care policy or who are expected to be admitted to the ICU with a terminal care policy within 24 hours of admission to the ICU 4. Patients who have expressed their refusal to have their clinical data used in research. **Minimum Age:** 16 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** The following Berlin definition of ARDS will be used 1. Acute onset (within 1 week of an apparent trigger or the appearance or worsening of respiratory symptoms) 2. Chest imaging (plain X-ray/CT) (pleural effusion, atelectasis, bilateral shadows that cannot be explained by nodules alone) 3. Causes of pulmonary edema (cannot be explained by cardiac insufficiency or excessive fluid infusion alone) 4. Impaired oxygenation (PEEP/CPAP ≥ 5 cmH2O and P/F ratio \< 300 mmHg) ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Kensuke Nakamura, MD, PhD **Phone:** ＋81-29-231-1111 **Role:** CONTACT #### Locations **Location 1:** **City:** Tokyo **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Kensuke Nakamura, MD, PhD - **Phone:** ＋81-29-231-1111 - **Role:** CONTACT **Country:** Japan **Facility:** LIBERATION Study Research Office **Status:** RECRUITING **Zip:** 102-0073 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000012120 - Term: Respiration Disorders - ID: D000007235 - Term: Infant, Premature, Diseases - ID: D000007232 - Term: Infant, Newborn, Diseases - ID: D000055370 - Term: Lung Injury ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14965 - Name: Respiratory Distress Syndrome - Relevance: HIGH - As Found: Respiratory Distress Syndrome - ID: M14964 - Name: Respiratory Distress Syndrome, Newborn - Relevance: HIGH - As Found: Respiratory Distress Syndrome - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M28144 - Name: Acute Lung Injury - Relevance: HIGH - As Found: Acute Respiratory Distress Syndrome - ID: M28143 - Name: Lung Injury - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: M25869 - Name: Premature Birth - Relevance: LOW - As Found: Unknown - ID: M10279 - Name: Infant, Premature, Diseases - Relevance: LOW - As Found: Unknown - ID: M10276 - Name: Infant, Newborn, Diseases - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: HIGH - As Found: Quality of Life - ID: T4927 - Name: Respiratory Distress Syndrome, Infant - Relevance: HIGH - As Found: Respiratory Distress Syndrome - ID: T192 - Name: Acute Respiratory Distress Syndrome - Relevance: HIGH - As Found: Acute Respiratory Distress Syndrome - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012128 - Term: Respiratory Distress Syndrome - ID: D000012127 - Term: Respiratory Distress Syndrome, Newborn - ID: D000055371 - Term: Acute Lung Injury - ID: D000013577 - Term: Syndrome ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04974879 **Brief Title:** Osimertinib Combined With Bevacizumab in the Treatment Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions Metastatic Non-Small Cell Lung Cancer **Official Title:** Osimertinib Combined With Bevacizumab in the Treatment Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions Local Advanced or Metastatic Non-Small Cell Lung Cancer #### Organization Study ID Info **ID:** QDCH2021-07-02 #### Organization **Class:** OTHER **Full Name:** Qingdao Central Hospital ### Status Module #### Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-03-29 **Type:** ACTUAL **Last Update Submit Date:** 2023-03-27 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-07-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-07-01 **Type:** ACTUAL **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2021-07-23 **Type:** ACTUAL **Study First Submit Date:** 2021-07-16 **Study First Submit QC Date:** 2021-07-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Qingdao Central Hospital #### Responsible Party **Investigator Affiliation:** Qingdao Central Hospital **Investigator Full Name:** Youxin Ji **Investigator Title:** chief **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** There is no muture method to treat EGFR 20 insertion mutation non-small-cell lung cancer (NSCLC). the he purpose of this study is to study osimertinib combined with bevacizumab in the management of it. **Detailed Description:** Lung cancer is one of the most common types of cancer and is the most common cause of death from cancer (almost 20 percent \[%\] of cancer deaths); NSCLC accounts for 80% to 85% of lung cancers. The hypothesis is that osimertinib combined bevacizumab in patients with locally advanced or metastatic NSCLC characterized by EGFR Exon 20ins activating mutations. Efficacy assessments will include disease assessment, symptomatic progression and patient-reported outcome. Safety assessments will include physical examinations, vital signs, electrocardiograms (ECGs), Eastern Cooperative Oncology Group (ECOG) performance status and clinical safety laboratory assessments (serum chemistry, hematology, coagulation, and urinalysis). ### Conditions Module **Conditions:** - Carcinoma, Non-Small-Cell Lung **Keywords:** - Bronchial Neoplasms - EGFR Exon20ins Mutation ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** osimertinib oral and bevazizumab intravenously ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** osimertinib oral daily and bevacizumab 15mg/KG body weight intravenously infusion every 21 days. **Intervention Names:** - Drug: Osimertinib Oral Tablet **Label:** study drug **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - study drug **Description:** Osimertinib, 80mg, oral daily; bevacizumab (avastin), 15mg/KG body weight, erery 21 days, intravenously. **Name:** Osimertinib Oral Tablet **Other Names:** - bevacizumab **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Progression-Free Survival (PFS) According to RECIST v1.1 as Assessed by Blinded Independent Central Review (BICR) **Measure:** Progression free survival **Time Frame:** 18 months #### Secondary Outcomes **Description:** ORR is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as defined by BICR using RECIST v1.1 criteria. **Measure:** Objective Response Rate (ORR) **Time Frame:** Up to 48 months **Description:** Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause. **Measure:** Overall Survival (OS) **Time Frame:** Up to 48 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Participant must have histologically or cytologically confirmed, locally advanced or metastatic, nonsquamous non-small cell lung cancer (NSCLC) with documented primary epidermal growth factor receptor (EGFR) Exon 20ins activating mutation Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, or 2 Participant must agree to genetic characterization of tumor status through the required pretreatment tumor biopsy (or submission of equivalent archival material), as well as baseline and periodic blood samples for analysis of tumor mutations in the bloodstream A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study Exclusion Criteria: Participant has history of spinal cord compression that has not been treated definitively with surgery or radiation Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD, or radiation pneumonitis Participant has a contraindication to the use Osimertinib or Bevacizumab **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Qingdao **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** youxin ji, M.D. - **Phone:** 8653268665078 - **Role:** CONTACT ***Contact 2:*** - **Name:** ketao lan, M.D. - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** chunling zhang, M.D. - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** youxin ji, M.D. - **Role:** SUB_INVESTIGATOR **Country:** China **Facility:** Qingdao Central Hospital, Qingdao Cancer Hospital **State:** Shandong **Status:** RECRUITING **Zip:** 266042 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms - ID: D000008175 - Term: Lung Neoplasms - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M11172 - Name: Lung Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: HIGH - As Found: Carcinoma, Non-Small-Cell Lung - ID: M5260 - Name: Bronchial Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002289 - Term: Carcinoma, Non-Small-Cell Lung ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000092004 - Term: Tyrosine Kinase Inhibitors - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M246 - Name: Bevacizumab - Relevance: LOW - As Found: Unknown - ID: M145673 - Name: Osimertinib - Relevance: HIGH - As Found: Facility - ID: M11900 - Name: Mitogens - Relevance: LOW - As Found: Unknown - ID: M2889 - Name: Tyrosine Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: T22 - Name: Tyrosine - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000596361 - Term: Osimertinib ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04955379 **Brief Title:** Study in Pediatric Volunteers of a Handheld Device Versus a Standard Diagnostic Device in Ophthalmic Refraction **Official Title:** An Exploratory Study in Healthy Pediatric Volunteers to Evaluate the Performance of a Handheld Device Compared With Standard Eye Care Diagnostic Device in Measuring Ophthalmic Refraction #### Organization Study ID Info **ID:** EYEQUE-005 #### Organization **Class:** INDUSTRY **Full Name:** EyeQue Corp. ### Status Module #### Completion Date **Date:** 2023-07-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-01-30 **Type:** ACTUAL **Last Update Submit Date:** 2023-01-26 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-07-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-12-15 **Type:** ACTUAL **Status Verified Date:** 2023-01 #### Study First Post Date **Date:** 2021-07-08 **Type:** ACTUAL **Study First Submit Date:** 2021-06-28 **Study First Submit QC Date:** 2021-07-06 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** Sheba Medical Center #### Lead Sponsor **Class:** INDUSTRY **Name:** EyeQue Corp. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is exploratory and examines whether the refraction results obtained from a novel optical device yields results similar to the ophthalmic refraction measurements obtained from an autorefractor in children. **Detailed Description:** This study is exploratory and examines whether the refraction results obtained from a novel optical device yields results similar to the ophthalmic refraction measurements obtained from an autorefractor in the age stratum of 6 through 17 years. ### Conditions Module **Conditions:** - Refractive Errors - Accomodation - Diagnostic Self Evaluation **Keywords:** - Refraction - Telehealth - Vision - Accommodation ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will be tested with the Autorefractor and the EQ103 device **Intervention Names:** - Device: EQ103 **Label:** Measurements **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Measurements **Description:** Ophthalmic Refractometer with a measurement and background channel **Name:** EQ103 **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Tendency of, or achieving, statistical equivalence of refraction measurements EQ103 (non-cycloplegic) compared with autorefractor (non-cycloplegic) **Measure:** Tendency of, or achieving, statistical equivalence of refraction measurements EQ103 (non-cycloplegic) compared with autorefractor (non-cycloplegic) **Time Frame:** Day 1 #### Secondary Outcomes **Description:** EyeQue EQ103 (non-cycloplegic) and the autorefractor (cycloplegic) assessed by refractive error measured by each device analyzed in the following age-strata. Age Groups * 6 to 12 y.o. \>12 to \<18 y.o. **Measure:** EyeQue EQ103 (non-cycloplegic) and the autorefractor (cycloplegic) assessed by refractive error measured by each device analyzed by age-strata. **Time Frame:** Day 1 and 14 **Description:** EyeQue EQ103 (non-cycloplegic) and the autorefractor (cycloplegic) assessed by refractive error measured by each device analyzed in the following age-strata. Age Group * 6 to 12 y.o. **Measure:** EyeQue EQ103 (non-cycloplegic) and the autorefractor (cycloplegic) assessed by refractive error measured by each device analyzed by age-strata. **Time Frame:** Day 1 and 14 **Description:** EQ103 without cycloplegia will be compared to EQ103 with cycloplegia in the following age-strata. Age Group * 6 to 12 y.o. **Measure:** EQ103 without cycloplegia will be compared to EQ103 with cycloplegia by younger age-strata. **Time Frame:** Day 1 and 14 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or Female * Ages ≥6 y.o. and \<18 y.o. * Binocular vision * Parent(s) or Guardian(s) willing and able to give informed consent on behalf of the subject. * Subject able to follow all study procedures and requirements Exclusion Criteria: * Spherical correction \> +8 or \< -10 * Using anticholinergic medications (including first-generation antihistamines) or other medications known to affect visual acuity within the greater of 3 days or 5 half-lives prior to enrolling in this study. * Using an investigational drug or approved therapy for investigational use within the greater of 3 days or 5 half-lives prior to enrolling in this study. * Has initiated any new medication in the past 2 weeks that, in the best medical judgment of the investigator, would impact their participation in the study or ability to use the EyeQue EQ103 device, * Any self/caregiver-reported mental illness or condition of the subject, including but not limited to claustrophobia, fear of simulators, nyctophobia. * Any self/caregiver-reported neurological diseases of the subject, including but not limited to: epilepsy, nystagmus. * Any self/caregiver-reported glaucoma diagnosis of the subject. * Eye disease, including but not limited to: * Cataracts * Macular degeneration * Eye infection (by self-report or observation) * Keratoconus * Diabetic neuropathy/retinopathy * Cytomegalovirus retinitis * Color blindness (any color deficiency) * Diabetic macular edema * Amblyopia * Chronic or acute uveitis * Strabismus * Astigmatism \> 3 diopters * Macular hole * Lack physical dexterity to properly operate the EyeQue device. * Lack the ability to follow instruction. * Lack binocular vision. * Are colorblind. * Had eye surgery within the last 12 months. **Healthy Volunteers:** True **Maximum Age:** 17 Years **Minimum Age:** 6 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Noam Sapiens, PhD **Phone:** (510) 953-6433 **Phone Ext:** 600 **Role:** CONTACT **Contact 2:** **Name:** Ygal Rotenstreich **Phone:** (408) 630-5086 **Role:** CONTACT #### Locations **Location 1:** **City:** Tel HaShomer **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ygal Rotenstreich - **Phone:** +972-527485888 - **Role:** CONTACT **Country:** Israel **Facility:** Sheba Medical Center **Status:** RECRUITING **Zip:** 5262100 #### Overall Officials **Official 1:** **Affiliation:** Sponsor GmbH **Name:** Noam Sapiens, PhD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14872 - Name: Refractive Errors - Relevance: HIGH - As Found: Refractive Errors - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012030 - Term: Refractive Errors ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01581879 **Brief Title:** Bioequivalence Study of Ziprasidone HCL Capsules, 20 mg of Dr. Reddy's Under Fed Conditions **Official Title:** Randomized, 2-way Crossover, Bioequivalence Study of Ziprasidone HCL Capsules, 20 mg in Healthy Subjects Under Fed Conditions. #### Organization Study ID Info **ID:** 40350 #### Organization **Class:** INDUSTRY **Full Name:** Dr. Reddy's Laboratories Limited ### Status Module #### Completion Date **Date:** 2005-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-04-20 **Type:** ESTIMATED **Last Update Submit Date:** 2012-04-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2004-11 **Type:** ACTUAL #### Start Date **Date:** 2004-11 **Status Verified Date:** 2012-04 #### Study First Post Date **Date:** 2012-04-20 **Type:** ESTIMATED **Study First Submit Date:** 2012-04-19 **Study First Submit QC Date:** 2012-04-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Dr. Reddy's Laboratories Limited #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The objective of this study is to compare the rate and extent of absorption of ziprasidone 20 mg capsules versus Geodon 20 mg capsules under fed conditions. **Detailed Description:** Randomized, 2-way crossover, bioequivalence study of Ziprasidone 20 mg capsules and Geodon 20 mg capsules in healthy subjects under fed conditions. ### Conditions Module **Conditions:** - Healthy **Keywords:** - Bioequivalence - Ziprasidone hydrochloride - crossover ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 38 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Ziprasidone HCL Capsules, 20 mg of Dr. Reddy's Laboratories Limited **Intervention Names:** - Drug: Ziprasidone Hydrochloride **Label:** Ziprasidone HCL Capsules, 20 mg **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Geodon Capsules, 20 mg of Pfizer Inc **Intervention Names:** - Drug: Ziprasidone Hydrochloride **Label:** Geodon Capsules, 20 mg **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Geodon Capsules, 20 mg - Ziprasidone HCL Capsules, 20 mg **Description:** Ziprasidone HCL Capsules, 20 mg **Name:** Ziprasidone Hydrochloride **Other Names:** - Geodon **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Area under curve (AUC) **Time Frame:** 1, 2, 3, 3.50, 4, 4.50, 5, 5.50, 6, 6.50, 7, 8, 9, 10, 12, 16, 24 and 36 hours post-dose ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female, smoker or non-smoker, 18 years of age and older. * Capable of consent. * BMI between 19.0 and 30.0 kg/m2 inclusively. Exclusion Criteria: * Clinically significant illnesses within 4 weeks prior to the administration of the study medication. * Clinically significant surgery within 4 weeks prior to the administration of the study medication. * Any clinically significant abnormality found during medical screening. * Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study. * Abnormal laboratory tests judged clinically significant. * Positive testing for hepatitis B, hepatitis C, or HIV at screening. * ECG abnormalities (clinically significant) or vital sign abnormalities (systolic blood pressure lower than 100 or over 140 mmHg, diastolic blood pressure lower than 60 or over 90 mmHg, or heart rate less than 60 or over 100 bpm) at screening. * Qtc \> 430 for males and Qtc \> 450 for females. * History of significant alcohol abuse or drug abuse within one year prior to the screening visit. * Regular use of alcohol within six months prior to the screening visit ( more than fourteen units of alcohol per week \[1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol\]). * Use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine \[PCP\] and crack) within 1 year prior to the screening visit or positive urine drug screen at screening. * History of allergic reaction to heparin, ziprasidone, or other related drugs. * Use of any drugs known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; examples of inhibitors: antidepressants (SSRI), cimetidine, diltiazem, macrolides, imidazole, neuroleptics, verapamil, fluoroquinolones, antihistamines) within 30 days prior to administration of the study medication. * Use of an investigational drug or participation in an investigational study within 30 days prior to administration of the study medication. * Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms(e.g. diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug. * Any clinically significant history or presence of clinically significant neurological endocrinal cardiovascular, pulmonary, hematologic, immunologic, psychiatric, or metabolic disease. * Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products (including natural food supplements, vitamins, garlic as a supplement) within 7 days prior to administration of study medication, except for topical products without systemic absorption and hormonal contraceptives. * Difficulty to swallow study medication. * Smoking more than 25 cigarettes per day. * Any food allergy, intolerance, restriction or special diet that, in the opinion of the Medical Sub-Investigator, could contraindicate the subject's participation in this study. * A depot injection or an implant of any drug (other than hormonal contraceptives) within 3 months prior to administration of study medication. * Donation of plasma (500 mL) within 7 days prior to drug administration. Donation or loss of whole blood (excluding the volume of blood that will be drawn during the screening procedures of this study) prior to administration of the study medication as follows. 1. 50 mL to 300 mL of whole blood within 30 days, 2. 301 mL to 500 mL of whole blood within 45 days, or 3. more than 500 mL of whole blood within 56 days prior to drug administration. * Consumption of food or beverages containing grapefruit (e.g. fresh, canned, or frozen) within 7 days prior to administration of the study medication. * History or known presence of tardive dyskinesia. * History of neuroleptic malignant syndrome. * History or known presence of clinically significant cardiac diseases (such as heart failure, QT prolongation, congenital long QT syndrome, myocardial infarction, cardiac arrhythmias, conduction abnormalities) or other conditions such as electrolyte disturbance, hypokalemia or hypomagnesemia. * Breast-feeding subject. * Positive urine pregnancy test at screening. * Female subjects of childbearing potential having unprotected sexual intercourse with any non-steril male partner (i.e male who has not been sterilized by vasectomy for at least 6 months ) within 14 days prior to study drug administration. Acceptable methods of contraception. 1. intra-uterine contraceptive device (placed at least 4 weeks prior to study drug administration; 2. condom or diaphragm + spermicide; 3. hormonal contraceptives (starting at least 4 weeks prior to study drug administration. **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Fort Myers **Country:** United States **Facility:** SFBC Ft. Myers, Inc. **State:** Florida **Zip:** 33901 #### Overall Officials **Official 1:** **Affiliation:** SFBC Ft. Myers, Inc **Name:** Antonio R. Pizarro, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009748 - Term: Nutrition Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M25306 - Name: Malnutrition - Relevance: HIGH - As Found: Under Fed - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000044342 - Term: Malnutrition ### Intervention Browse Module - Ancestors - ID: D000012702 - Term: Serotonin Antagonists - ID: D000018490 - Term: Serotonin Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000014150 - Term: Antipsychotic Agents - ID: D000014149 - Term: Tranquilizing Agents - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000011619 - Term: Psychotropic Drugs - ID: D000018492 - Term: Dopamine Antagonists - ID: D000015259 - Term: Dopamine Agents ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: CaAg - Name: Cardiotonic Agents ### Intervention Browse Module - Browse Leaves - ID: M254665 - Name: Ziprasidone - Relevance: HIGH - As Found: Extragonadal germ cell tumor - ID: M15512 - Name: Serotonin - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M16904 - Name: Antipsychotic Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M7473 - Name: Dopamine - Relevance: LOW - As Found: Unknown - ID: M20596 - Name: Dopamine Antagonists - Relevance: LOW - As Found: Unknown - ID: M17962 - Name: Dopamine Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000092292 - Term: Ziprasidone ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02136979 **Brief Title:** Effect of Anesthetics on CD39 and CD73 After Open-heart Surgery **Official Title:** Effect of Propofol and Sevoflurane on Serum CD39 and CD73 Level After Open Heart Surgery With Cardiopulmonary Bypass #### Organization Study ID Info **ID:** KUH1160064 #### Organization **Class:** OTHER **Full Name:** Konkuk University Medical Center ### Status Module #### Completion Date **Date:** 2017-08-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-01-18 **Type:** ACTUAL **Last Update Submit Date:** 2018-01-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-12-31 **Type:** ACTUAL #### Start Date **Date:** 2014-05-21 **Type:** ACTUAL **Status Verified Date:** 2018-01 #### Study First Post Date **Date:** 2014-05-13 **Type:** ESTIMATED **Study First Submit Date:** 2014-05-07 **Study First Submit QC Date:** 2014-05-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Konkuk University Medical Center #### Responsible Party **Investigator Affiliation:** Konkuk University Medical Center **Investigator Full Name:** Seong-Hyop Kim **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** CD39 and CD73 was known protein expressed on surface of Th1 and Th17 cell and modulate immune related reaction. Cardiopulmonary bypass (CPB) can induce inflammatory reaction during cardiac surgery, and induce immunosuppression. Propofol and volatile anesthetics were related to immune reaction. However, the effect of propofol and sevoflurane on the change of CD39 and CD73 after CPB was not evaluated in previous studies. The authors hypothesized that the expression of CD39 and CD73 would differ between propofol- and volatile anaesthetic-based anaesthesia in patients undergoing CPB. Therefore, the present study determined the effect of propofol and sevoflurane on CD39 and CD73 during and after CPB. **Detailed Description:** After obtaining permission of the Institutional Review Board of Konkuk University Medical Center, Seoul, South Korea , patients scheduled to undergo elective cardiac surgery under cardiopulmonary bypass (CPB) after signed written informed consent agreements and prospectively participate in the present study. All patients got a cardiac surgery under moderate hypothermic cardiopulmonary bypass (CPB) by one cardiac surgeon. Also, 6ml of blood and sample was obtained for total 5 times in consecutive order. 1. Before operation (pre-CPB1) 2. 15 minute after successful CPB weaning (post-CPB1) 3. 3 hrs after CPB weaning (post-CPB2) 4. 24 hrs after CPB weaning (post-CPB3) 5. 48 hrs after CPB weaning (post-CPB4) The following intraoperative exclusion criteria are applied: 1. Emergency operation that could not obtain pre-CPB1 sample 2. Patients who have infectious factor before operation 3. Patients who have immunosuppressive agent for underlying disease before operation 4. Patients who have history of cancer previously 5. Patients who are younger than 19 years old Using blood sample, authors examined as follows 1. Flow cytometry for Th 17 and Th 1 cell. 2. Immunocytochemistry for CD39, CD73. 3. Assay for IL 1,6,10,17,IFN-γ, and TNF-α 4. patient vital sign during operation 5. other laboratory tests Statistical analyses are conducted using SPSS 20.0 (SPSS Inc., Chicago, IL, USA). CD39 and CD73 are analysed used a Repeated Measures Analysis of Variance and their pairwise multiple comparisons are performed via the tukey method. The comparisons of the other continuous variables are performed by paired t or Wilcoxon Signed Rank tests. Data are expressed as mean ± SD (95% confidence interval. CI) or median (25%-75%), and number of the patients. A p value less than 0.05 is considered statistically significant. ### Conditions Module **Conditions:** - Valvular Heart Disease - Aortic Disease ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** FACTORIAL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 2 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** patients with propofol-based anesthesia **Intervention Names:** - Drug: Propofol **Label:** Propofol group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** patients with sevoflurane-based anesthesia **Intervention Names:** - Drug: Sevoflurane **Label:** Sevoflurane group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Propofol group **Description:** group of patients with propofol-based anesthesia **Name:** Propofol **Other Names:** - Propofol group **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Sevoflurane group **Description:** group of patients with sevoflurane-based anesthesia **Name:** Sevoflurane **Other Names:** - Sevoflurane group **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The difference of CD39 and CD73 level between propofol and sevoflurane group **Measure:** The level of CD39 and CD73 between propofol and sevoflurane group after CPB **Time Frame:** from preoperative status up to 48 hrs after CPB weaning status ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. patients scheduled to undergo elective cardiac surgery 2. signed written informed consent agreements Exclusion Criteria: 1. Emergency operation that could not obtain pre-CPB1 sample 2. Patients who have infectious factor before operation 3. Patients who have immunosuppressive agent for underlying disease before operation 4. Patients who have history of cancer previously 5. Patients who are younger than 19 years old **Maximum Age:** 90 Years **Minimum Age:** 19 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Konkuk University Medical Center **Zip:** 143-729 #### Overall Officials **Official 1:** **Affiliation:** Konkuk University Medical Center **Name:** Seong-Hyop Kim, M.D, Ph.D **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000014652 - Term: Vascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9419 - Name: Heart Diseases - Relevance: HIGH - As Found: Heart Disease - ID: M9437 - Name: Heart Valve Diseases - Relevance: HIGH - As Found: Valvular Heart Disease - ID: M4334 - Name: Aortic Diseases - Relevance: HIGH - As Found: Aortic Diseases - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006331 - Term: Heart Diseases - ID: D000006349 - Term: Heart Valve Diseases - ID: D000001018 - Term: Aortic Diseases ### Intervention Browse Module - Ancestors - ID: D000006993 - Term: Hypnotics and Sedatives - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018686 - Term: Anesthetics, Intravenous - ID: D000018681 - Term: Anesthetics, General - ID: D000000777 - Term: Anesthetics - ID: D000010975 - Term: Platelet Aggregation Inhibitors - ID: D000018685 - Term: Anesthetics, Inhalation ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PlAggInh - Name: Platelet Aggregation Inhibitors ### Intervention Browse Module - Browse Leaves - ID: M18307 - Name: Propofol - Relevance: HIGH - As Found: COVID-19 - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M1673 - Name: Sevoflurane - Relevance: HIGH - As Found: Metabolic - ID: M10043 - Name: Hypnotics and Sedatives - Relevance: LOW - As Found: Unknown - ID: M20766 - Name: Anesthetics, Intravenous - Relevance: LOW - As Found: Unknown - ID: M20761 - Name: Anesthetics, General - Relevance: LOW - As Found: Unknown - ID: M13865 - Name: Platelet Aggregation Inhibitors - Relevance: LOW - As Found: Unknown - ID: M20765 - Name: Anesthetics, Inhalation - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000015742 - Term: Propofol - ID: D000077149 - Term: Sevoflurane ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02974179 **Brief Title:** A Long Term Follow-up Study of AMG0001 in Subjects With Critical Limb Ischemia **Official Title:** A Long Term Follow-up Study of AMG0001 in Subjects With Critical Limb Ischemia #### Organization Study ID Info **ID:** AG-CLI-0206-LTFU #### Organization **Class:** INDUSTRY **Full Name:** AnGes USA, Inc. #### Secondary ID Infos **ID:** 2016-003491-41 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2020-01-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-12 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-01-10 **Type:** ACTUAL #### Start Date **Date:** 2017-02-20 **Type:** ACTUAL **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2016-11-28 **Type:** ESTIMATED **Study First Submit Date:** 2016-11-23 **Study First Submit QC Date:** 2016-11-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** AnGes USA, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** Subjects from the AG-CLI-0206 phase 3 study that received AMG0001 will be eligible for the AG-CLI-0206-LTFU study **Detailed Description:** The study is designed to assess the long term safety of subjects who have been treated in the phase 3 study with AMG0001. A health questionnaire will be used to collect specific information from the subject every 6 months. Only those subjects that were randomized in the AG-CLI-0206 study and who received AMG0001 are eligible to participate in this long term follow-up study. Subjects that received placebo will not be eligible for participation in this study. ### Conditions Module **Conditions:** - Critical Limb Ischemia ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 9 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects from Study AG-CLI-0206 who received the study product AMG0001 **Intervention Names:** - Biological: Subjects from Study AG-CLI-0206 who received AMG0001 **Label:** Subjects who received AMG0001 ### Interventions #### Intervention 1 **Arm Group Labels:** - Subjects who received AMG0001 **Description:** Subjects from Study AG-CLI-0206 who received the study product AMG0001 **Name:** Subjects from Study AG-CLI-0206 who received AMG0001 **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** A health questionnaire will be used to collect specific information from the subject every 6 months **Measure:** Assess the long term safety of subjects from the AG-CLI-0206 study who have been treated with AMG0001 **Time Frame:** 3 years from the date last subject randomized into AG-CLI-0206 study ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects who have been treated with AMG0001 in the AG-CLI-0206 study. * Subjects who have provided consent for this long term follow-up study either directly or through a legally authorized representative. * Subjects who have provided a release of information to the sponsor. Exclusion Criteria: * Subjects who were not enrolled in the AGCLI-0206 study. * Subjects who enrolled in AG-CLI-0206 and who were not treated with AMG0001. * Subjects who have not provided consent to this long term follow-up study either directly or through a legally authorized representative. * Subjects who have not provided a release of information for the Sponsor to contact them directly via phone, email and/or mail. **Maximum Age:** 90 Years **Minimum Age:** 40 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Subjects with critical limb ischemia who have previously been treated with AMG0001 in the AG-CLI-0206 study. ### Contacts Locations Module #### Locations **Location 1:** **City:** Lebanon **Country:** United States **Facility:** Dartmouth-Hitchcock Medical Center **State:** New Hampshire **Zip:** 03756 #### Overall Officials **Official 1:** **Affiliation:** Dartmouth-Hitchcock Medical Center **Name:** Richard Powell, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000058729 - Term: Peripheral Arterial Disease - ID: D000050197 - Term: Atherosclerosis - ID: D000001161 - Term: Arteriosclerosis - ID: D000001157 - Term: Arterial Occlusive Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000016491 - Term: Peripheral Vascular Diseases - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10543 - Name: Ischemia - Relevance: HIGH - As Found: Ischemia - ID: M2714 - Name: Chronic Limb-Threatening Ischemia - Relevance: HIGH - As Found: Critical Limb Ischemia - ID: M29213 - Name: Peripheral Arterial Disease - Relevance: LOW - As Found: Unknown - ID: M18894 - Name: Peripheral Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M26188 - Name: Atherosclerosis - Relevance: LOW - As Found: Unknown - ID: M4469 - Name: Arteriosclerosis - Relevance: LOW - As Found: Unknown - ID: M4465 - Name: Arterial Occlusive Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000089802 - Term: Chronic Limb-Threatening Ischemia - ID: D000007511 - Term: Ischemia ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03759379 **Brief Title:** HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis) **Official Title:** HELIOS-A: A Phase 3 Global, Randomized, Open-label Study to Evaluate the Efficacy and Safety of ALN-TTRSC02 in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis) #### Organization Study ID Info **ID:** ALN-TTRSC02-002 #### Organization **Class:** INDUSTRY **Full Name:** Alnylam Pharmaceuticals #### Secondary ID Infos **ID:** 2018-002098-23 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2026-10 **Type:** ESTIMATED #### Disp First Post Date **Date:** 2021-11-15 **Type:** ACTUAL **Disp First Submit Date:** 2021-11-09 **Disp First Submit QC Date:** 2021-11-09 #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-20 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-18 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2020-11-10 **Type:** ACTUAL #### Results First Post Date **Date:** 2022-08-11 **Type:** ACTUAL **Results First Submit Date:** 2022-07-12 **Results First Submit QC Date:** 2022-07-12 #### Start Date **Date:** 2019-02-14 **Type:** ACTUAL **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2018-11-30 **Type:** ACTUAL **Study First Submit Date:** 2018-11-28 **Study First Submit QC Date:** 2018-11-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Alnylam Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to evaluate the efficacy and safety of vutrisiran (ALN-TTRSC02) in participants with hereditary transthyretin amyloidosis (hATTR amyloidosis). Participants will receive vutrisiran subcutaneous (SC) injection once every 3 months (q3M) or the reference comparator patisiran intravenous (IV) injection once every 3 weeks (q3w) during the 18 month Treatment Period. This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints during the 18 Month Treatment Period. Following the 18 Month Treatment Period, all participants will be randomized to receive vutrisiran SC injection once every 6 months (q6M) or q3M in the Randomized Treatment Extension (RTE) Period. ### Conditions Module **Conditions:** - Amyloidosis, Hereditary - Transthyretin Amyloidosis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 164 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection once every 6 months (q6M) or q3M during the Randomized Treatment Extension (RTE) Period. **Intervention Names:** - Drug: Vutrisiran **Label:** Vutrisiran + Vutrisiran (HELIOS-A) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. **Intervention Names:** - Drug: Patisiran - Drug: Vutrisiran **Label:** Patisiran + Vutrisiran (HELIOS-A) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Patisiran + Vutrisiran (HELIOS-A) **Description:** Patisiran will be administered by IV infusion. **Name:** Patisiran **Other Names:** - ONPATTRO - ALN-TTR02 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Patisiran + Vutrisiran (HELIOS-A) - Vutrisiran + Vutrisiran (HELIOS-A) **Description:** Vutrisiran will be administered by SC injection. **Name:** Vutrisiran **Other Names:** - ALN-TTRSC02 - AMVUTTRA **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome. **Measure:** Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Time Frame:** Baseline, Month 9 #### Secondary Outcomes **Description:** The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome. **Measure:** Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Time Frame:** Baseline, Month 9 **Description:** The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening. **Measure:** Change From Baseline in the Timed 10-Meter Walk Test (10-MWT) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Time Frame:** Baseline, Month 9 **Description:** The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome. **Measure:** Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Time Frame:** Baseline, Month 18 **Description:** The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome. **Measure:** Change From Baseline in Norfolk QoL-DN Total Score at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Time Frame:** Baseline, Month 18 **Description:** The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening. **Measure:** Change From Baseline in the 10-MWT at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Time Frame:** Baseline, Month 18 **Description:** The mBMI, which is a measure of nutritional status, is calculated as the product of body mass index (BMI) (weight in kilograms divided by the square of height in meters) and serum albumin (g/L) to reflect fluid balance, such as fluid accumulation or dehydration. A negative change from baseline indicates a better outcome. **Measure:** Change From Baseline in the Modified Body Mass Index (mBMI) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Time Frame:** Baseline, Month 18 **Description:** The R-ODS is a patient-reported measure of level of disability on a scale of 0-48, with 0 being the worst and 48 the best (no limitations); scores are based on activities of daily living and social participation. An increase in R-ODS from baseline suggests improvement in disability, and a decrease from baseline suggests worsening of disability. **Measure:** Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Time Frame:** Baseline, Month 18 **Description:** Serum TTR was assessed at multiple timepoints up to Month 18. **Measure:** Percent Reduction in Serum Transthyretin (TTR) Levels Through Month 18 Between the Vutrisiran Group (HELIOS-A) and the Patisiran Group (HELIOS-A) **Time Frame:** Up to Month 18 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female of 18 to 85 years of age (inclusive); * Has a diagnosis of hATTR amyloidosis with transthyretin (TTR) mutation; * Has adequate neurologic impairment score (NIS); * Has adequate polyneuropathy disability (PND) score; * Has adequate Karnofsky Performance Status (KPS). Exclusion Criteria: * Had a prior liver transplant or is likely to undergo liver transplantation during the study; * Has known other (non-hATTR) forms of amyloidosis or leptomeningeal amyloidosis; * Has New York Heart Association heart failure classification \>2; * Clinically significant liver function test abnormalities; * Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; * Received an experimental drug within 30 days of dosing; * Received prior TTR-lowering treatment; * Has other known causes of neuropathy. **Maximum Age:** 85 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Diego **Country:** United States **Facility:** Clinical Trial Site **State:** California **Zip:** 92120 **Location 2:** **City:** Aurora **Country:** United States **Facility:** Clinical Trial Site **State:** Colorado **Zip:** 80045 **Location 3:** **City:** Chicago **Country:** United States **Facility:** Clinical Trial Site **State:** Illinois **Zip:** 97239 **Location 4:** **City:** Baltimore **Country:** United States **Facility:** Clinical Trial Site **State:** Maryland **Zip:** 21205 **Location 5:** **City:** Boston **Country:** United States **Facility:** Clinical Trial Site **State:** Massachusetts **Zip:** 02118 **Location 6:** **City:** Rochester **Country:** United States **Facility:** Clinical Trial Site **State:** Minnesota **Zip:** 55905 **Location 7:** **City:** Saint Louis **Country:** United States **Facility:** Clinical Trial Site **State:** Missouri **Zip:** 63130 **Location 8:** **City:** New York **Country:** United States **Facility:** Clinical Trial Site **State:** New York **Zip:** 10032 **Location 9:** **City:** Chapel Hill **Country:** United States **Facility:** Clinical Trial Site **State:** North Carolina **Zip:** 27599 **Location 10:** **City:** Columbus **Country:** United States **Facility:** Clinical Trial Site **State:** Ohio **Zip:** 43210 **Location 11:** **City:** Portland **Country:** United States **Facility:** Clinical Trial Site **State:** Oregon **Zip:** 97239 **Location 12:** **City:** Philadelphia **Country:** United States **Facility:** Clinical Trial Site **State:** Pennsylvania **Zip:** 19140 **Location 13:** **City:** Fort Worth **Country:** United States **Facility:** Clinical Trial Site **State:** Texas **Zip:** 75246 **Location 14:** **City:** Buenos Aires **Country:** Argentina **Facility:** Clinical Trial Site **Location 15:** **City:** Box Hill **Country:** Australia **Facility:** Clinical Trial Site **Location 16:** **City:** Westmead **Country:** Australia **Facility:** Clinical Trial Site **Location 17:** **City:** Woolloongabba **Country:** Australia **Facility:** Clinical Trial Site **Location 18:** **City:** Bruxelles **Country:** Belgium **Facility:** Clinical Trial Site **Location 19:** **City:** Leuven **Country:** Belgium **Facility:** Clinical Trial Site **Location 20:** **City:** Rio De Janeiro **Country:** Brazil **Facility:** Clinical Trial Site **Location 21:** **City:** Sofia **Country:** Bulgaria **Facility:** Clinical Trial Site **Location 22:** **City:** Montréal **Country:** Canada **Facility:** Clinical Trial Site **Location 23:** **City:** Vancouver **Country:** Canada **Facility:** Clinical Trial Site **Location 24:** **City:** Nicosia **Country:** Cyprus **Facility:** Clinical Trial Site **Location 25:** **City:** Bordeaux **Country:** France **Facility:** Clinical Trial Site **Location 26:** **City:** Créteil **Country:** France **Facility:** Clinical Trial Site **Location 27:** **City:** Marseille **Country:** France **Facility:** Clinical Trial Site **Location 28:** **City:** Paris **Country:** France **Facility:** Clinical Trial Site **Location 29:** **City:** Mainz **Country:** Germany **Facility:** Clinical Trial Site **Location 30:** **City:** Münster **Country:** Germany **Facility:** Clinical Trial Site **Location 31:** **City:** Athens **Country:** Greece **Facility:** Clinical Trial Site **Location 32:** **City:** Messina **Country:** Italy **Facility:** Clinical Trial Site **Location 33:** **City:** Pavia **Country:** Italy **Facility:** Clinical Trial Site **Location 34:** **City:** Rome **Country:** Italy **Facility:** Clinical Trial Site **Location 35:** **City:** Kumamoto **Country:** Japan **Facility:** Clinical Trial Site **Location 36:** **City:** Nagano **Country:** Japan **Facility:** Clinical Trial Site **Location 37:** **City:** Nagoya **Country:** Japan **Facility:** Clinical Trial Site **Location 38:** **City:** Osaka **Country:** Japan **Facility:** Clinical Trial Site **Location 39:** **City:** Junggu **Country:** Korea, Republic of **Facility:** Clinical Trial Site **Location 40:** **City:** Kuala Lumpur **Country:** Malaysia **Facility:** Clinical Trial Site **Location 41:** **City:** Mexico City **Country:** Mexico **Facility:** Clinical Trial Site **Location 42:** **City:** Groningen **Country:** Netherlands **Facility:** Clinical Trial Site **Location 43:** **City:** Lisboa **Country:** Portugal **Facility:** Clinical Trial Site **Location 44:** **City:** Porto **Country:** Portugal **Facility:** Clinical Trial Site **Location 45:** **City:** Barcelona **Country:** Spain **Facility:** Clinical Trial Site **Location 46:** **City:** Huelva **Country:** Spain **Facility:** Clinical Trial Site **Location 47:** **City:** Madrid **Country:** Spain **Facility:** Clinical Trial Site **Location 48:** **City:** Valencia **Country:** Spain **Facility:** Clinical Trial Site **Location 49:** **City:** Solna **Country:** Sweden **Facility:** Clinical Trial Site **Location 50:** **City:** Umeå **Country:** Sweden **Facility:** Clinical Trial Site **Location 51:** **City:** Taipei City **Country:** Taiwan **Facility:** Clinical Trial Site **Location 52:** **City:** Taipei **Country:** Taiwan **Facility:** Clinical Trial Site **Location 53:** **City:** London **Country:** United Kingdom **Facility:** Clinical Trial Site #### Overall Officials **Official 1:** **Affiliation:** Alnylam Pharmaceuticals **Name:** Medical Director **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Adams D, Tournev IL, Taylor MS, Coelho T, Plante-Bordeneuve V, Berk JL, Gonzalez-Duarte A, Gillmore JD, Low SC, Sekijima Y, Obici L, Chen C, Badri P, Arum SM, Vest J, Polydefkis M; HELIOS-A Collaborators. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023 Mar;30(1):1-9. doi: 10.1080/13506129.2022.2091985. Epub 2022 Jul 23. **PMID:** 35875890 ## Document Section ### Large Document Module #### Large Docs - Date: 2021-02-19 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 9085902 - Type Abbrev: Prot - Upload Date: 2022-07-12T11:46 - Date: 2021-08-24 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 8347637 - Type Abbrev: SAP - Upload Date: 2022-07-12T11:51 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000057165 - Term: Proteostasis Deficiencies - ID: D000008659 - Term: Metabolic Diseases - ID: D000020271 - Term: Heredodegenerative Disorders, Nervous System - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000017772 - Term: Amyloid Neuropathies - ID: D000010523 - Term: Peripheral Nervous System Diseases - ID: D000009468 - Term: Neuromuscular Diseases - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000008661 - Term: Metabolism, Inborn Errors ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M4021 - Name: Amyloidosis - Relevance: HIGH - As Found: Amyloidosis - ID: M23330 - Name: Amyloid Neuropathies, Familial - Relevance: HIGH - As Found: Transthyretin Amyloidosis - ID: M19981 - Name: Amyloid Neuropathies - Relevance: LOW - As Found: Unknown - ID: M23329 - Name: Amyloidosis, Familial - Relevance: HIGH - As Found: Amyloidosis, Hereditary - ID: M28747 - Name: Proteostasis Deficiencies - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M22092 - Name: Heredodegenerative Disorders, Nervous System - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M13432 - Name: Peripheral Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M12411 - Name: Neuromuscular Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M11641 - Name: Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: T2264 - Name: Familial Transthyretin Amyloidosis - Relevance: HIGH - As Found: Transthyretin Amyloidosis - ID: T340 - Name: Amyloid Neuropathy - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000028227 - Term: Amyloid Neuropathies, Familial - ID: D000028226 - Term: Amyloidosis, Familial - ID: D000000686 - Term: Amyloidosis ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020). #### Event Groups **Group ID:** EG000 **Title:** Vutrisiran + Vutrisiran (HELIOS-A) **Deaths Num Affected:** 2 **Deaths Num At Risk:** 122 **Description:** Participants will receive vutrisiran 25 mg SC injection q3M for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. **ID:** EG000 **Other Num Affected:** 78 **Other Num at Risk:** 122 **Serious Number Affected:** 21 **Serious Number At Risk:** 122 **Title:** Vutrisiran + Vutrisiran (HELIOS-A) **Group ID:** EG001 **Title:** Patisiran + Vutrisiran (HELIOS-A) **Deaths Num Affected:** 3 **Deaths Num At Risk:** 42 **Description:** Participants will receive patisiran 0.3 mg/kg IV infusion q3w for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. **ID:** EG001 **Other Num Affected:** 31 **Other Num at Risk:** 42 **Serious Number Affected:** 17 **Serious Number At Risk:** 42 **Title:** Patisiran + Vutrisiran (HELIOS-A) **Frequency Threshold:** 5 #### Other Events **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Oedema peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) **Term:** Ligament sprain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) **Term:** Vitamin A decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Neuralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (23.0) #### Serious Events **Term:** Acute myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Arrhythmia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Atrioventricular block complete **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Cardiac failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Cardiac failure acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Cardiac failure chronic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Cardiac failure congestive **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 42 **Term:** Cardiogenic shock **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Conduction disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Myocardial ischaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Ventricular tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Vertigo **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Cyclic vomiting syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Upper gastrointestinal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Asthenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Infusion site phlebitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 42 **Term:** COVID-19 **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** COVID-19 pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Endocarditis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Escherichia urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Infusion site cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 42 **Term:** Kidney infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Pyelonephritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Vestibular neuronitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Femur fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Foot fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 42 **Term:** Fractured sacrum **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Post procedural complication **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Cardiovascular evaluation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Investigation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Dyslipidaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Fluid overload **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Hypokalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Endometrial neoplasm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Cerebrovascular accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Neuralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Syncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Renal failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Hospitalisation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 42 **Term:** Iliac artery occlusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Term:** Orthostatic hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 42 **Time Frame:** Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 241 **Units:** Participants ### Group **ID:** BG000 **Title:** External Placebo Comparator (APOLLO) **Description:** Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo. ### Group **ID:** BG001 **Title:** Vutrisiran + Vutrisiran (HELIOS-A) **Description:** Participants will receive vutrisiran 25 mg SC injection q3M for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. ### Group **ID:** BG002 **Title:** Patisiran + Vutrisiran (HELIOS-A) **Description:** Participants will receive patisiran 0.3 mg/kg IV infusion q3w for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. ### Group **ID:** BG003 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG001 **Spread:** 13.2 **Value:** 57.8 #### Measurement **Group ID:** BG002 **Spread:** 10.5 **Value:** 58.0 #### Measurement **Group ID:** BG003 **Spread:** 12.5 **Value:** 57.9 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 10.76 **Value:** 62.2 #### Measurement **Group ID:** BG003 **Spread:** 10.76 **Value:** 62.2 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 77 **Class Title:** ### Measure #### Measurement **Group ID:** BG001 **Value:** 43 #### Measurement **Group ID:** BG002 **Value:** 15 #### Measurement **Group ID:** BG003 **Value:** 58 **Category Title:** Female #### Measurement **Group ID:** BG001 **Value:** 79 #### Measurement **Group ID:** BG002 **Value:** 27 #### Measurement **Group ID:** BG003 **Value:** 106 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 19 #### Measurement **Group ID:** BG003 **Value:** 19 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 58 #### Measurement **Group ID:** BG003 **Value:** 58 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 77 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 21 #### Measurement **Group ID:** BG002 **Value:** 8 #### Measurement **Group ID:** BG003 **Value:** 29 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 8 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** Multiple #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 11 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** Other #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** Unknown #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 86 #### Measurement **Group ID:** BG002 **Value:** 29 #### Measurement **Group ID:** BG003 **Value:** 115 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** White ### Measure #### Measurement **Group ID:** BG000 **Value:** 25 #### Measurement **Group ID:** BG003 **Value:** 25 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 77 **Class Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 1 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 77 **Class Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 50 #### Measurement **Group ID:** BG003 **Value:** 50 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 77 **Class Title:** White #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 1 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 77 **Class Title:** Unknown or Not Reported ### Measure #### Measurement **Group ID:** BG001 **Spread:** 35.99 **Value:** 60.55 #### Measurement **Group ID:** BG002 **Spread:** 33.71 **Value:** 57.69 #### Measurement **Group ID:** BG003 **Spread:** 35.34 **Value:** 59.82 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 42 **Group ID:** BG003 **Value:** 164 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 37.041 **Value:** 74.61 #### Measurement **Group ID:** BG003 **Spread:** 37.041 **Value:** 74.61 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 77 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below. **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately. **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below. **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately. **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below. **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ### Measure 6 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately. **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ### Measure 7 **Description:** The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below. **Title:** Modified Neuropathy Impairment Score +7 (mNIS+7) **Unit of Measure:** score on a scale ### Measure 8 **Description:** The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately. **Title:** Modified Neuropathy Impairment Score +7 (mNIS+7) **Unit of Measure:** score on a scale **Population Description:** Safety Population: all participants who received any amount of study drug. Data from the placebo arm of the APOLLO study (NCT01960348) is included as it will be used as an external comparator for the primary and most other efficacy endpoints. The placebo APOLLO arm did not participate in this study. ## Results Section - More Information Module ### Certain Agreement **Other Details:** It is intended that after completion of the study, the data are to be submitted for publication in a scientific journal and/or for reporting at a scientific meeting. A copy of any proposed publication (eg, manuscript, abstracts, oral/slide presentations, book chapters) based on this study, must be provided and confirmed/received at the Sponsor at least 30 days before its submission. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Alnylam Pharmaceuticals Inc. **Phone:** 866-330-0326 **Title:** Chief Medical Officer ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -21.78 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -12.22 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.44 **Estimate Comment:** **Group Description:** Multiple imputation estimates and p-value derived per combining least squares (LS) estimates per Rubin's rules based on 100 datasets where missing Month 9 values were imputed using a regression procedure including select baseline variables. LS estimates derived from analysis of covariance model, controlling for categorical factors (treatment, genotype, age of disease onset) and continuous covariate (baseline value). **Non-Inferiority Comment:** H0: No difference between vutrisiran and external placebo comparator (APOLLO): difference (vutrisiran - placebo) = 0 **Non-Inferiority Type:** EQUIVALENCE **Other Analysis Description:** **P-Value:** <0.0000001 **P-Value Comment:** P=3.542E-12 **Parameter Type:** LS Mean Difference **Parameter Value:** -17.00 **Statistical Comment:** **Statistical Method:** ANCOVA with Multiple Imputation **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -21.7 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -10.8 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.8 **Estimate Comment:** **Group Description:** Multiple imputation estimates and p-value derived per combining least squares (LS) estimates per Rubin's rules based on 100 datasets where missing Month 9 values were imputed using a regression procedure including select baseline variables. LS estimates derived from analysis of covariance model, controlling for categorical factors (treatment, genotype, age of disease onset baseline NIS) and continuous covariate (baseline value). **Non-Inferiority Comment:** H0: No difference between vutrisiran and external placebo comparator (APOLLO): difference (vutrisiran - placebo) = 0 **Non-Inferiority Type:** EQUIVALENCE **Other Analysis Description:** **P-Value:** <0.0000001 **P-Value Comment:** P=5.426E-09 **Parameter Type:** LS Mean Difference **Parameter Value:** -16.2 **Statistical Comment:** **Statistical Method:** ANCOVA with Multiple Imputation **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 0.070 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.193 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.031 **Estimate Comment:** **Group Description:** Multiple imputation estimates and p-value derived per combining least squares (LS) estimates per Rubin's rules based on 100 datasets where missing Month 9 values were imputed using a regression procedure including select baseline variables. LS estimates derived from analysis of covariance model, controlling for categorical factors (treatment, genotype, age of disease onset, baseline NIS) and continuous covariate (baseline value). **Non-Inferiority Comment:** H0: No difference between vutrisiran and external placebo comparator (APOLLO): difference (vutrisiran - placebo) = 0 **Non-Inferiority Type:** EQUIVALENCE **Other Analysis Description:** **P-Value:** <0.0000001 **P-Value Comment:** P=3.103E-05 **Parameter Type:** LS Mean Difference **Parameter Value:** 0.131 **Statistical Comment:** **Statistical Method:** ANCOVA with Multiple Imputation **Tested Non-Inferiority:** ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.00 - **Upper Limit:** - **Value:** 14.76 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.43 - **Upper Limit:** - **Value:** -2.24 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** 12.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.7 - **Upper Limit:** - **Value:** -3.3 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.025 - **Upper Limit:** - **Value:** -0.133 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.019 - **Upper Limit:** - **Value:** -0.001 **Title:** #### Outcome Measure 4 #### Outcome Measure 5 #### Outcome Measure 6 #### Outcome Measure 7 #### Outcome Measure 8 #### Outcome Measure 9 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized. **Reporting Status:** POSTED **Time Frame:** Baseline, Month 9 **Title:** Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Type:** PRIMARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo. **ID:** OG000 **Title:** External Placebo Comparator (APOLLO) ##### Group **Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period. **ID:** OG001 **Title:** Vutrisiran + Vutrisiran (HELIOS-A) #### Outcome Measure 2 **Description:** The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized. **Reporting Status:** POSTED **Time Frame:** Baseline, Month 9 **Title:** Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo. **ID:** OG000 **Title:** External Placebo Comparator (APOLLO) ##### Group **Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period. **ID:** OG001 **Title:** Vutrisiran + Vutrisiran (HELIOS-A) #### Outcome Measure 3 **Description:** The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized. **Reporting Status:** POSTED **Time Frame:** Baseline, Month 9 **Title:** Change From Baseline in the Timed 10-Meter Walk Test (10-MWT) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Type:** SECONDARY **Unit of Measure:** m/sec ##### Group **Description:** Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo. **ID:** OG000 **Title:** External Placebo Comparator (APOLLO) ##### Group **Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection during the Randomized Treatment Extension (RTE) Period. **ID:** OG001 **Title:** Vutrisiran + Vutrisiran (HELIOS-A) #### Outcome Measure 4 **Description:** The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome. **Reporting Status:** NOT_POSTED **Time Frame:** Baseline, Month 18 **Title:** Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Type:** SECONDARY #### Outcome Measure 5 **Description:** The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome. **Reporting Status:** NOT_POSTED **Time Frame:** Baseline, Month 18 **Title:** Change From Baseline in Norfolk QoL-DN Total Score at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Type:** SECONDARY #### Outcome Measure 6 **Description:** The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening. **Reporting Status:** NOT_POSTED **Time Frame:** Baseline, Month 18 **Title:** Change From Baseline in the 10-MWT at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Type:** SECONDARY #### Outcome Measure 7 **Description:** The mBMI, which is a measure of nutritional status, is calculated as the product of body mass index (BMI) (weight in kilograms divided by the square of height in meters) and serum albumin (g/L) to reflect fluid balance, such as fluid accumulation or dehydration. A negative change from baseline indicates a better outcome. **Reporting Status:** NOT_POSTED **Time Frame:** Baseline, Month 18 **Title:** Change From Baseline in the Modified Body Mass Index (mBMI) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Type:** SECONDARY #### Outcome Measure 8 **Description:** The R-ODS is a patient-reported measure of level of disability on a scale of 0-48, with 0 being the worst and 48 the best (no limitations); scores are based on activities of daily living and social participation. An increase in R-ODS from baseline suggests improvement in disability, and a decrease from baseline suggests worsening of disability. **Reporting Status:** NOT_POSTED **Time Frame:** Baseline, Month 18 **Title:** Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)] **Type:** SECONDARY #### Outcome Measure 9 **Description:** Serum TTR was assessed at multiple timepoints up to Month 18. **Reporting Status:** NOT_POSTED **Time Frame:** Up to Month 18 **Title:** Percent Reduction in Serum Transthyretin (TTR) Levels Through Month 18 Between the Vutrisiran Group (HELIOS-A) and the Patisiran Group (HELIOS-A) **Type:** SECONDARY ### Participant Flow Module #### Group **Description:** Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran SC injection once every 6 months (q6M) or q3M during the Randomized Treatment Extension (RTE) Period. **ID:** FG000 **Title:** Vutrisiran + Vutrisiran (HELIOS-A) #### Group **Description:** Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. **ID:** FG001 **Title:** Patisiran + Vutrisiran (HELIOS-A) #### Period **Title:** Treatment Period ##### Withdraw **Type:** Remained in this Period at Time of Data Cut ###### Reason **Group ID:** FG000 **Number of Subjects:** 119 ###### Reason **Group ID:** FG001 **Number of Subjects:** 38 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 42 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 42 #### Period **Title:** Randomized Treatment Extension Period ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Pre-Assignment Details:** This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints (N=77). **Recruitment Details:** Participants with hATTR amyloidosis were enrolled and treated at 57 sites in Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Cyprus, France, Germany, Greece, Italy, Japan, Korea, Malaysia, Mexico, Netherlands, Portugal, Spain, Sweden, Taiwan, United Kingdom and United States. Data is reported for the 9-Month primary analysis period. **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT04960579 **Acronym:** MM **Brief Title:** P-BCMA-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Multiple Myeloma **Official Title:** Open-Label, Multicenter, Phase 1 Study to Assess the Safety of P-BCMA-ALLO1 in Subjects With Relapsed / Refractory Multiple Myeloma (MM) #### Organization Study ID Info **ID:** P-BCMA-ALLO1-001 #### Organization **Class:** INDUSTRY **Full Name:** Poseida Therapeutics, Inc. ### Status Module #### Completion Date **Date:** 2039-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-27 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2027-12 **Type:** ESTIMATED #### Start Date **Date:** 2022-05-05 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2021-07-14 **Type:** ACTUAL **Study First Submit Date:** 2021-06-24 **Study First Submit QC Date:** 2021-07-09 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Roche-Genentech #### Lead Sponsor **Class:** INDUSTRY **Name:** Poseida Therapeutics, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** Phase 1 study comprised of open-label, dose escalation, multiple cohorts of P-BCMA-ALLO1 allogeneic T stem cell memory (Tscm) CAR-T cells in subjects with relapsed / refractory Multiple Myeloma (RRMM). **Detailed Description:** Phase 1/1b study: Phase 1 Part 1 is a weight-based dose escalation following a 3+3 design of dose-escalating cohorts. Phase 1 Part 2 includes administration at fixed doses. After enrollment, subjects may receive a lymphodepletion therapy regimen before administration of allogeneic CAR-T cells, administered as a single or multiple doses. Treated subjects will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated. Phase 1b of the study will undergo further expansion of cohorts/arms from Phase 1 Parts 1 or 2 to guide selection of Recommended Phase 2 Dose (RP2D). ### Conditions Module **Conditions:** - Multiple Myeloma ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 231 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm S) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen F. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm F) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Single weight-based IV administration of P-BCMA-ALLO1. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm N) **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P1. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm P1) **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P2. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm P2) **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen R. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm R) **Type:** EXPERIMENTAL #### Arm Group 7 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RS. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm RS) **Type:** EXPERIMENTAL #### Arm Group 8 **Description:** Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen C. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm C) **Type:** EXPERIMENTAL #### Arm Group 9 **Description:** Single fixed dose IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S, P1, P1.5 or P2. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm160) **Type:** EXPERIMENTAL #### Arm Group 10 **Description:** Single fixed dose IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S, P1, P1.5 or P2. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm480) **Type:** EXPERIMENTAL #### Arm Group 11 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P1.5. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm P1.5) **Type:** EXPERIMENTAL #### Arm Group 12 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP1. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm RP1) **Type:** EXPERIMENTAL #### Arm Group 13 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP1.5. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm RP1.5) **Type:** EXPERIMENTAL #### Arm Group 14 **Description:** Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP2. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm RP2) **Type:** EXPERIMENTAL #### Arm Group 15 **Description:** Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP1. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm CP1) **Type:** EXPERIMENTAL #### Arm Group 16 **Description:** Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP1.5. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm CP1.5) **Type:** EXPERIMENTAL #### Arm Group 17 **Description:** Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP2. Rimiducid may be administered as indicated. **Intervention Names:** - Biological: P-BCMA-ALLO1 CAR-T cells - Drug: Rimiducid **Label:** P-BCMA-ALLO1 CAR-T cells (Arm CP2) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - P-BCMA-ALLO1 CAR-T cells (Arm C) - P-BCMA-ALLO1 CAR-T cells (Arm CP1) - P-BCMA-ALLO1 CAR-T cells (Arm CP1.5) - P-BCMA-ALLO1 CAR-T cells (Arm CP2) - P-BCMA-ALLO1 CAR-T cells (Arm F) - P-BCMA-ALLO1 CAR-T cells (Arm N) - P-BCMA-ALLO1 CAR-T cells (Arm P1) - P-BCMA-ALLO1 CAR-T cells (Arm P1.5) - P-BCMA-ALLO1 CAR-T cells (Arm P2) - P-BCMA-ALLO1 CAR-T cells (Arm R) - P-BCMA-ALLO1 CAR-T cells (Arm RP1) - P-BCMA-ALLO1 CAR-T cells (Arm RP1.5) - P-BCMA-ALLO1 CAR-T cells (Arm RP2) - P-BCMA-ALLO1 CAR-T cells (Arm RS) - P-BCMA-ALLO1 CAR-T cells (Arm S) - P-BCMA-ALLO1 CAR-T cells (Arm160) - P-BCMA-ALLO1 CAR-T cells (Arm480) **Description:** Allogeneic BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy **Name:** P-BCMA-ALLO1 CAR-T cells **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - P-BCMA-ALLO1 CAR-T cells (Arm C) - P-BCMA-ALLO1 CAR-T cells (Arm CP1) - P-BCMA-ALLO1 CAR-T cells (Arm CP1.5) - P-BCMA-ALLO1 CAR-T cells (Arm CP2) - P-BCMA-ALLO1 CAR-T cells (Arm F) - P-BCMA-ALLO1 CAR-T cells (Arm N) - P-BCMA-ALLO1 CAR-T cells (Arm P1) - P-BCMA-ALLO1 CAR-T cells (Arm P1.5) - P-BCMA-ALLO1 CAR-T cells (Arm P2) - P-BCMA-ALLO1 CAR-T cells (Arm R) - P-BCMA-ALLO1 CAR-T cells (Arm RP1) - P-BCMA-ALLO1 CAR-T cells (Arm RP1.5) - P-BCMA-ALLO1 CAR-T cells (Arm RP2) - P-BCMA-ALLO1 CAR-T cells (Arm RS) - P-BCMA-ALLO1 CAR-T cells (Arm S) - P-BCMA-ALLO1 CAR-T cells (Arm160) - P-BCMA-ALLO1 CAR-T cells (Arm480) **Description:** Safety switch activator **Name:** Rimiducid **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Rate of dose limiting toxicities (DLT) **Measure:** Phase 1 Part 1: Assess the safety and maximum tolerated dose (MTD) of P-BCMA-ALLO1 based on dose limiting toxicities (DLT) **Time Frame:** Baseline through Day 28 **Description:** Frequency and severity of adverse events, including cytokine release syndrome. **Measure:** Phase 1 Part 2: Assess the safety and tolerability of P-BCMA-ALLO1 when administered as a fixed dose of cells. **Time Frame:** Baseline through 36 months **Description:** Incidence and severity of cytokine release syndrome (CRS) events graded using American Society for Transplantation and Cellular Therapy (ASTCT) criteria (Lee, 2019). **Measure:** Phase 1b: The effect of cell dose and study arm to guide selection of Recommended Phase 2 Dose (RP2D). **Time Frame:** Baseline through 36 months #### Secondary Outcomes **Description:** Incidence and severity of treatment-emergent adverse events **Measure:** The safety of P-BCMA-ALLO1 **Time Frame:** Baseline through 15 years **Description:** According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Overall Response Rate (ORR) - Percentage of patients with complete response (CR), very good partial response (VGPR), or partial response (PR) **Measure:** The anti-myeloma effect of P-BCMA-ALLO1 (ORR) in Phase 1 Parts 1 and 2 **Time Frame:** Baseline through 15 years **Description:** According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Time to Response (TTR) - Time to complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease **Measure:** The anti-myeloma effect of P-BCMA-ALLO1 (TTR) **Time Frame:** Baseline through 15 years **Description:** According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Duration of Response - Time from complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease **Measure:** The anti-Myeloma effect of P-BCMA-ALLO1 (DOR) **Time Frame:** Baseline through 15 years **Description:** According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Progression Free Survival (PFS) - Time from P-BCMA-ALLO1 treatment to progressive disease **Measure:** The anti-Myeloma effect of P-BCMA-ALLO1 (PFS) **Time Frame:** Baseline through 15 years **Description:** According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Overall Survival (OS) - Duration of survival from time of treatment with P-BCMA-ALLO1 **Measure:** The anti-Myeloma effect of P-BCMA-ALLO1 (OS) **Time Frame:** Baseline through 15 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Must have signed written, informed consent. 2. Males or females, ≥18 years of age. 3. Must have a confirmed diagnosis of active MM. 4. Must have measurable MM. 5. Must have relapsed / refractory MM, having received treatment with a proteasome inhibitor, immunomodulatory agent (IMiD), and anti-CD38 therapy. 6. Must be willing to practice birth control from the time of Screening and throughout the first year of the study after P-BCMA-ALLO1 administration. 7. Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test within 3 days prior to initiating the lymphodepletion therapy regimen (females of childbearing potential). 8. Must be at least 90 days since autologous stem cell transplant, if performed. 9. Must have adequate vital organ function within pre-determined parameters. 10. Must have recovered from toxicities due to prior therapies. 11. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Exclusion Criteria: 1. Is pregnant or lactating. 2. Has inadequate venous access. 3. Has active hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, or amyloidosis. 4. Has an active second malignancy (not disease-free for at least 5 years) in addition to MM, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma. 5. Has active autoimmune disease. 6. Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy, etc. 7. Has an active systemic infection. 8. Has a history of hepatitis B, hepatitis C virus, human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome. Subjects with a history of treated hepatitis C can be enrolled if negative by Hepatitis C PCR on multiple occasions and with medical monitor approval. 9. Is positive for cytomegalovirus (CMV) by PCR, CMV immunoglobulin M (IgM) antibody, or Coronavirus disease 2019 (COVID-19) by PCR. 10. Has New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of myocardial infarction or significant arrhythmia. 11. Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol. 12. Has received prior allogeneic cellular therapy or gene therapy. 13. Has received anti-cancer medications within 2 weeks of the time of initiating conditioning LD therapy. 14. Has received monoclonal antibody therapy within 4 weeks of initiating conditioning LD therapy. 15. Has received immunosuppressive medications within 2 weeks of the time of administration of P-BCMA-ALLO1, and/or expected to require them while on study. 16. Has received systemic corticosteroid therapy within 1 week or 5 half-lives (whichever is shorter) of the administration of P-BCMA-ALLO1 or is expected to require it during the course of the study. 17. Has CNS metastases or symptomatic CNS involvement of their myeloma. 18. Has a history of severe immediate hypersensitivity reaction to any of the agents used in this study. 19. Has a history of having undergone allogeneic stem cell transplantation, or any other allogeneic or xenogeneic transplant, or has undergone autologous transplantation within 90 days. 20. Arms R, RS, RP1, RP1.5 and RP2 Only: a) Has received a live vaccine within the last 28 days of the first administration of agents used in Arm R or RS, b) Has any known hypersensitivity or severe reactions or toxicity to agents used in Arms R or RS. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Angie Schinkel **Phone:** 858-779-3103 **Role:** CONTACT #### Locations **Location 1:** **City:** San Diego **Country:** United States **Facility:** University of California San Diego **State:** California **Status:** RECRUITING **Zip:** 92093 **Location 2:** **City:** San Francisco **Country:** United States **Facility:** University of California San Francisco **State:** California **Status:** TERMINATED **Zip:** 94143 **Location 3:** **City:** Park Ridge **Country:** United States **Facility:** Advocate Aurora Health **State:** Illinois **Status:** TERMINATED **Zip:** 66068 **Location 4:** **City:** Iowa City **Country:** United States **Facility:** University of Iowa **State:** Iowa **Status:** RECRUITING **Zip:** 52242 **Location 5:** **City:** Kansas City **Country:** United States **Facility:** University of Kansas Medical Center **State:** Kansas **Status:** RECRUITING **Zip:** 66160 **Location 6:** **City:** Baltimore **Country:** United States **Facility:** University of Maryland Greenebaum Comprehensive Cancer Center **State:** Maryland **Status:** RECRUITING **Zip:** 21201 **Location 7:** **City:** Detroit **Country:** United States **Facility:** Wayne State - Karmanos Cancer Institute **State:** Michigan **Status:** RECRUITING **Zip:** 48201 **Location 8:** **City:** Buffalo **Country:** United States **Facility:** Roswell Park Comprehensive Cancer Center **State:** New York **Status:** RECRUITING **Zip:** 14263 **Location 9:** **City:** Cincinnati **Country:** United States **Facility:** University of Cincinnati **State:** Ohio **Status:** RECRUITING **Zip:** 45221 **Location 10:** **City:** Oklahoma City **Country:** United States **Facility:** University of Oklahoma, Health Sciences Center **State:** Oklahoma **Status:** ACTIVE_NOT_RECRUITING **Zip:** 73104 **Location 11:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt University Medical Center **State:** Tennessee **Status:** RECRUITING **Zip:** 37232 **Location 12:** **City:** Austin **Country:** United States **Facility:** Sarah Cannon Research Institute - St. David's South Austin Medical Center **State:** Texas **Status:** RECRUITING **Zip:** 78704 **Location 13:** **City:** Houston **Country:** United States **Facility:** Houston Methodist Research Institute **State:** Texas **Status:** RECRUITING **Zip:** 77030 **Location 14:** **City:** San Antonio **Country:** United States **Facility:** Sarah Cannon Research Institute - Methodist Healthcare **State:** Texas **Status:** RECRUITING **Zip:** 78229 #### Overall Officials **Official 1:** **Affiliation:** Vice President, Clinical Development **Name:** Rajesh Belani, M.D. **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000020141 - Term: Hemostatic Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010265 - Term: Paraproteinemias - ID: D000001796 - Term: Blood Protein Disorders - ID: D000006402 - Term: Hematologic Diseases - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12058 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: M27588 - Name: Neoplasms, Plasma Cell - Relevance: HIGH - As Found: Multiple Myeloma - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M13178 - Name: Paraproteinemias - Relevance: LOW - As Found: Unknown - ID: M5077 - Name: Blood Protein Disorders - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T3947 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma ### Condition Browse Module - Meshes - ID: D000009101 - Term: Multiple Myeloma - ID: D000054219 - Term: Neoplasms, Plasma Cell ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04341779 **Brief Title:** Simplifying Treatment and Monitoring for HIV (STREAM HIV) **Official Title:** Simplifying Treatment and Monitoring for HIV (STREAM HIV): Point-of-Care Urine Tenofovir Adherence and Viral Load Testing to Improve HIV Outcomes in South Africa #### Organization Study ID Info **ID:** STUDY00007544 #### Organization **Class:** OTHER **Full Name:** University of Washington #### Secondary ID Infos **ID:** R01AI147752 **Link:** https://reporter.nih.gov/quickSearch/R01AI147752 **Type:** NIH ### Status Module #### Completion Date **Date:** 2024-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-14 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2021-02-04 **Type:** ACTUAL **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2020-04-10 **Type:** ACTUAL **Study First Submit Date:** 2020-04-07 **Study First Submit QC Date:** 2020-04-07 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Allergy and Infectious Diseases (NIAID) **Class:** NETWORK **Name:** Centre for the AIDS Programme of Research in South Africa #### Lead Sponsor **Class:** OTHER **Name:** University of Washington #### Responsible Party **Investigator Affiliation:** University of Washington **Investigator Full Name:** Paul Drain **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study seeks to determine the clinical efficacy and cost effectiveness of implementing an integrated model for HIV monitoring using point of care (POC) tenofovir (TFV) adherence testing and POC viral load (VL) monitoring in improving ART adherence, maintaining durable VL suppression, and improving retention in care among HIV-positive individuals initiating first-line tenofovir disoproxil fumarate (TDF)-based ART in South Africa. **Detailed Description:** This study will be a two-arm, open-label, randomized controlled superiority trial at an HIV clinic in Durban. HIV-positive individuals aged 16 years and above, who are initiating a tenofovir-based, first-line ART will be randomized to receive POC VL testing and POC TFV adherence testing, versus standard-of-care (SoC) viral load testing. The schedule for VL testing and management of VL test results will follow South African guidelines for HIV VL testing after ART initiation. 540 participants will be randomized (1:1) at ART initiation into the intervention arm (routine POC TFV adherence testing with POC VL monitoring) or the standard-of-care (SoC) arm (no objective TFV adherence testing and SoC VL monitoring). Participants will be followed to compare concentrations between study arms at 24 weeks after ART initiation and a composite outcome of VL suppression and retention in care between the study arms at 72 weeks after ART initiation. The study will use process evaluation data, interviews and focus groups with patients and staff to assess implementation of the POC assays. Micro-costing will be conducted to estimate intervention costs. ### Conditions Module **Conditions:** - HIV/AIDS - HIV-1-infection **Keywords:** - Point-of-care test - Tenofovir - Adherence - HIV viral load ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 540 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Point-of-care adherence testing and Point-of-care viral load testing **Intervention Names:** - Combination Product: Point-of-care viral load testing and tenofovir adherence testing **Label:** Intervention arm **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No adherence testing and lab-based viral load testing **Label:** Standard-of-care arm **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention arm **Description:** Point-of-care testing of HIV viral load and tenofovir, and providing same day results to participants **Name:** Point-of-care viral load testing and tenofovir adherence testing **Type:** COMBINATION_PRODUCT ### Outcomes Module #### Primary Outcomes **Description:** We will measure tenofovir-diphosphate concentrations in 3mm dried blood spots using liquid chromatography/tandem mass spectrometry. **Measure:** Mean tenofovir diphosphate concentration levels in dried blood spots **Time Frame:** 24 weeks after ART initiation **Description:** We will measure viral load by a laboratory-based reference assay, performed by the South African National Health Laboratory Services. Viral suppression will be defined as a viral load \<200 copies/mL. Retention in care will be defined as having collected ART from the study clinic within 8 weeks of study exit. **Measure:** Combined measure of virological suppression and retention in care (binary) **Time Frame:** 72 weeks after ART initiation #### Secondary Outcomes **Description:** We will measure viral load by a laboratory-based reference assay, performed by the South African National Health Laboratory Services. Viral suppression will be defined as a viral load \<200 copies/mL. Retention in care will be defined as having collected ART from the study clinic within 8 weeks of their 6-month study visit. **Measure:** Combined measure of viral suppression and retention in care (binary) **Time Frame:** 24 weeks after ART initiation **Description:** We will measure tenofovir-diphosphate concentrations in 3mm dried blood spots using liquid chromatography/tandem mass spectrometry. **Measure:** Tenofovir-diphosphate concentration in dried blood spots (continuous) **Time Frame:** 72 weeks after ART initiation **Description:** We will assess acceptability of point-of-care tenofovir and viral load testing by conducting semi-structured in-depth interviews and focus group discussions with study participants. **Measure:** Acceptability of point-of-care tenofovir and viral load testing **Time Frame:** 24 and 72 weeks after ART initiation **Description:** We will conduct a micro-costing of the costs associated with point-of-care tenofovir and viral load testing and will estimate the cost-effectiveness of the intervention using an existing individual-based, stochastic HIV model for KwaZulu-Natal for simulating health and economic outcomes. **Measure:** Cost-effectiveness of providing routine point-of-care tenofovir and viral load testing as compared to standard-of-care viral load monitoring **Time Frame:** 24 and 72 weeks after ART initiation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * HIV-positive * ≥16 years old * Initiating a TDF-based, first-line ART regimen * Do not self-report being on an ART regimen in the prior month * Willing/able to provide written informed consent Exclusion Criteria: * Does not plan to continue receiving HIV care at the CDC Clinic * Per the decision or opinion of the PI (for example, a clinically significant acute or chronic medical condition or circumstances that would make the patient unsuitable for participation or jeopardize the safety or rights of the participant **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Zarna Marfatia **Phone:** +12065203800 **Role:** CONTACT #### Locations **Location 1:** **City:** Durban **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Pedzisai Munatsi - **Phone:** +27 (0)31 655 0604 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Nigel Garrett, MBBS, PhD - **Phone:** +27312604453 - **Role:** CONTACT ***Contact 3:*** - **Name:** Nigel Garrett, MBBS, PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** South Africa **Facility:** Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal **State:** KwaZulu-Natal **Status:** RECRUITING **Zip:** 4013 #### Overall Officials **Official 1:** **Affiliation:** University of Washington **Name:** Paul Drain, MD, MPH **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Centre for the AIDS Programme of Research in South Africa (CAPRISA) **Name:** Nigel Garett, MBBS, PHD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** De-identified data generated under this project will be administered in accordance with University of Washington, CAPRISA, and NIH policies, including the NIH Data Sharing Policy and Implementation Guidance of March 5, 2003. **Description:** De-identified data from the study will be made available **Info Types:** - STUDY_PROTOCOL - ICF **IPD Sharing:** YES **Time Frame:** Beginning 9 months and ending 36 months following publication of primary results. ### References Module #### References **Citation:** Bardon AR, Dorward J, Sookrajh Y, Sayed F, Quame-Amaglo J, Pillay C, Feutz E, Ngobese H, Simoni JM, Sharma M, Cressey TR, Gandhi M, Lessells R, Moodley P, Naicker N, Naidoo K, Thomas K, Celum C, Abdool Karim S, Garrett N, Drain PK. Simplifying TREAtment and Monitoring for HIV (STREAM HIV): protocol for a randomised controlled trial of point-of-care urine tenofovir and viral load testing to improve HIV outcomes. BMJ Open. 2021 Oct 5;11(10):e050116. doi: 10.1136/bmjopen-2021-050116. **PMID:** 34610939 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000086982 - Term: Blood-Borne Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections - ID: D000015229 - Term: Sexually Transmitted Diseases, Viral - ID: D000012749 - Term: Sexually Transmitted Diseases - ID: D000016180 - Term: Lentivirus Infections - ID: D000012192 - Term: Retroviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000012897 - Term: Slow Virus Diseases - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000007153 - Term: Immunologic Deficiency Syndromes - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: HIGH - As Found: HIV/AIDS - ID: M18250 - Name: HIV Infections - Relevance: HIGH - As Found: HIV/AIDS - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M10199 - Name: Immunologic Deficiency Syndromes - Relevance: LOW - As Found: Unknown - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M15558 - Name: Sexually Transmitted Diseases - Relevance: LOW - As Found: Unknown - ID: M17933 - Name: Sexually Transmitted Diseases, Viral - Relevance: LOW - As Found: Unknown - ID: M18640 - Name: Lentivirus Infections - Relevance: LOW - As Found: Unknown - ID: M15026 - Name: Retroviridae Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M15700 - Name: Slow Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000163 - Term: Acquired Immunodeficiency Syndrome - ID: D000015658 - Term: HIV Infections ### Intervention Browse Module - Ancestors - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000018894 - Term: Reverse Transcriptase Inhibitors - ID: D000019384 - Term: Nucleic Acid Synthesis Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000019380 - Term: Anti-HIV Agents - ID: D000044966 - Term: Anti-Retroviral Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M296 - Name: Tenofovir - Relevance: HIGH - As Found: 1000 - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M20935 - Name: Reverse Transcriptase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M21350 - Name: Anti-HIV Agents - Relevance: LOW - As Found: Unknown - ID: M25428 - Name: Anti-Retroviral Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068698 - Term: Tenofovir ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01797679 **Brief Title:** Study of Cartilage Relaxometry and Physical Activity in Osteoarthritis **Official Title:** Efficacy of Strength and Aerobic Exercise on the Articular Cartilage of Patients With Mild and Moderate Knee Osteoarthritis Measured by T2 and T1 Rho MR Imaging - A Randomized Controlled Trial #### Organization Study ID Info **ID:** NFR213335/h10 #### Organization **Class:** OTHER **Full Name:** University Hospital, Akershus ### Status Module #### Completion Date **Date:** 2017-03 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2020-01-14 **Type:** ACTUAL **Last Update Submit Date:** 2020-01-10 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2014-12 **Type:** ESTIMATED #### Start Date **Date:** 2013-03 **Status Verified Date:** 2020-01 #### Study First Post Date **Date:** 2013-02-22 **Type:** ESTIMATED **Study First Submit Date:** 2013-02-21 **Study First Submit QC Date:** 2013-02-21 **Why Stopped:** Lack of agreement between the participants and lack og funding ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** The Research Council of Norway **Class:** OTHER **Name:** Oslo University Hospital **Class:** OTHER **Name:** Hjelp24 **Class:** OTHER **Name:** South-Eastern Norway Regional Health Authority #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Akershus #### Responsible Party **Investigator Affiliation:** University Hospital, Akershus **Investigator Full Name:** Hasan Banitalebi **Investigator Title:** Radiologist **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study is the radiological component of an earlier registered trial under the title: Efficacy of Exercise on Physical Function and Cartilage Health in Patients With Knee Osteoarthritis. The main purpose in this component of the study is to evaluate the efficacy of aerobic exercise and strength training on the T2 and T1 rho relaxation times of the articular cartilage. It has been proven that exercise can improve function and reduce the need for analgesics in patients with osteoarthritis. With this study, we wish to investigate if different kinds of exercise can cause measurable improvements in T2 and T1 rho relaxation times of the articular cartilage, and also if this improvements are transient or permanent. ### Conditions Module **Conditions:** - Osteoarthritis **Keywords:** - Osteoarthritis,Articular Cartilage, Relaxometry, Morphometry, MRI, T2 mapping, T1 rho ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The strength group include progressive strength training and neuromuscular exercises. The inclusion will be performed 2-3 times a week for 12 weeks. Intervention: Other: Strength training **Intervention Names:** - Other: Strength Training **Label:** Strength Training **Type:** OTHER #### Arm Group 2 **Description:** The aerobic exercise group will cycle on an ergometer bicycle 2-3 times a week for 12 weeks on moderate loading. The loading will be controlled by a heart rate monitor and is defined as 85% of maximal heart rate. **Intervention Names:** - Other: Aerobic Exercise **Label:** Aerobic exercise **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** The control group will do as usual. **Label:** Control Group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Strength Training **Name:** Strength Training **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Aerobic exercise **Name:** Aerobic Exercise **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Indirect cartilage morphology will by assessed by X-ray Direct cartilage morphology will be assessed by MRI morphometry The biochemical composition of the cartilage will be assessed by relaxometry (T2 and T1 rho relaxation times) **Measure:** Qualitative Cartilage Morphology Assessment **Time Frame:** One year #### Secondary Outcomes **Description:** Using semiquantitative techniques, the clinical manifestations of osteoarthritis assessed by MRI such as: cartilage lesions and bone marrow lesions will be assessed and quantified by MRI. **Measure:** Semiquantitative Cartilage Assessment **Time Frame:** One year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Women and men aged 45-65 years * Clinical knee OA according to the American College of Rheumatology Clinical Criteria 17 * Kellgren and Lawrence radiographic OA grade 2 and 3 (mild to moderate radiographic OA) Exclusion Criteria: * Severe knee OA according to the Kellgren and Lawrence classification (grade 4) * Other known major musculoskeletal impairments in the lower extremities or the back or prostheses in any joint of the lower extremities * Known coronary heart diseases or cancer * Body mass index \> 35 * Scheduled for surgery in any joint * Known mental or psychologic diseases * Known drug abuse * Persons who already perform sports related moderate physical activity more than two times a week * Contraindications for magnetic resonance imaging (specific point list at Diagnostic Imaging Division, Akershus University Hospital) * Not speaking Norwegian **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 45 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Lorenskog **Country:** Norway **Facility:** Akershus University Hospital **Zip:** 1478 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M12926 - Name: Osteoarthritis - Relevance: HIGH - As Found: Osteoarthritis - ID: M22168 - Name: Osteoarthritis, Knee - Relevance: LOW - As Found: Unknown - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010003 - Term: Osteoarthritis ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02148679 **Acronym:** GOURMET-HF **Brief Title:** Geriatric Out of Hospital Randomized Meal Trial in Heart Failure **Official Title:** Effects of Home-delivered Low-sodium Meals in Older Adults Following Heart Failure Hospitalization. #### Organization Study ID Info **ID:** HUM00083272 #### Organization **Class:** OTHER **Full Name:** University of Michigan #### Secondary ID Infos **ID:** R21AG047939 **Link:** https://reporter.nih.gov/quickSearch/R21AG047939 **Type:** NIH ### Status Module #### Completion Date **Date:** 2017-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-07-27 **Type:** ACTUAL **Last Update Submit Date:** 2017-07-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-05-21 **Type:** ACTUAL #### Start Date **Date:** 2014-05 **Type:** ACTUAL **Status Verified Date:** 2017-07 #### Study First Post Date **Date:** 2014-05-28 **Type:** ESTIMATED **Study First Submit Date:** 2014-05-23 **Study First Submit QC Date:** 2014-05-27 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** PurFoods, LLC **Class:** NIH **Name:** National Institute on Aging (NIA) #### Lead Sponsor **Class:** OTHER **Name:** University of Michigan #### Responsible Party **Investigator Affiliation:** University of Michigan **Investigator Full Name:** Scott L. Hummel **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Description Module **Brief Summary:** Study subjects will receive either pre-prepared, home-delivered DASH/SRD-compliant meals or attention control for 4 weeks after hospital discharge. **Detailed Description:** This is a three center, randomized, single-blind, attention controlled trial of 12 weeks total duration designed to determine the safety and efficacy of home-delivered sodium-restricted Dietary Approaches to Stop Hypertension (DASH/SRD)-compliant meals in older adults (age \>= 65 years) following discharge from a hospital admission for acutely decompensated heart failure. 66 subjects will be randomized in a 1:1 stratified fashion by gender and left ventricular ejection fraction (\< vs. ≥ 50%). 107 subjects yielded 66 randomized subjects. Study subjects will receive either pre-prepared, home-delivered DASH/SRD-compliant meals or attention control for 4 weeks after hospital discharge. The three study sites will be Columbia University Medical Center, the Ann Arbor Veterans Affairs Health System, and the University of Michigan Health System. Investigators will be blinded to group assignment, food diaries, and urinary electrolyte measurements until the completion of the study ### Conditions Module **Conditions:** - Heart Failure **Keywords:** - Heart Failure - Diet ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 107 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receive Heart Failure Society of America pamphlet, "How to eat a low sodium diet" at hospital discharge Study staff will phone patients at weeks 2 and 3 to confirm patients' understanding of dietary instructions Intervention: pre-prepared, home delivered DASH/SRD-compliant meals for 4 weeks after hospital discharge **Intervention Names:** - Other: DASH/SRD **Label:** DASH/SRD **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients receive Heart Failure Society of America pamphlet, "How to eat a low sodium diet" at hospital discharge Study staff will phone patients at weeks 2 and 3 to confirm patients' understanding of dietary instructions **Intervention Names:** - Other: DASH/SRD - Other: Usual care **Label:** Attention Control **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Attention Control - DASH/SRD **Description:** Study food for this investigation will be designed and prepared by PurFoods, LLC (Des Moines, IA) dietitians under the direction of Dr. Sam Beattie, Ph. D., and in consultation with research dietitians at the University of Michigan and Columbia University. Study patients randomized to food delivery will select from an available menu of meal options that adhere to nutritional targets as above. Study food will be pre-packaged for storage with preparation (typically microwave heating) to be completed at home by the subject, and will be delivered every 1 to 2 weeks under the direction of PurFoods. **Name:** DASH/SRD **Other Names:** - Mom's Meals **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Attention Control **Description:** Standardized advice to restrict dietary sodium intake to \< 2000 mg/day **Name:** Usual care **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The KCCQ, a self-administered 23-item instrument, assesses physical limitations, symptoms, self-efficacy, social interference, and overall QOL in HF patients. The KCCQ summary score ranges from 0-100, with higher scores indicating better QOL. The KCCQ summary score independently predicts clinical outcomes such as hospitalization and mortality in outpatients with HF, including those recently hospitalized for acute decompensation. It is a reliable and valid measure in HF patients that is more sensitive to change than other measures of QOL, and is especially responsive in patients with multiple comorbidities. A change in KCCQ score of 5 points is clinically significant and correlates with changes in clinical status, physical function, and outcomes. **Measure:** change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary scores for health-related QOL in patients with chronic HF **Time Frame:** from study enrollment to 4 weeks post-discharge #### Secondary Outcomes **Description:** Renal function and electrolytes will be assessed at baseline and 1 week post-discharge during a safety visit, in which vital signs and targeted physical examination for volume status will allow adjustment of diuretics as clinically indicated. The dietary intervention will be stopped in any patient who develops new or worsened renal impairment as defined by estimated glomerular filtration rate decrease of ≥50%, hyperkalemia (K \>5.7 mmol/L), syncope, or other serious adverse event deemed by the investigators to be related to study participation (note participants are inherently at high risk for rehospitalization or mortality, \~20-25% over the 4-week intervention period of the study, \~30-35% over the total 12-week term of the study). Patients randomized to food delivery will have study food intake suspended if hospitalized and resumed at discharge if no safety concerns as defined above. **Measure:** Safety Monitoring **Time Frame:** Baseline and 1 week post discharge **Description:** Dietary endpoints will include DASH/SRD adherence as measured by 3-day food diary and urinary electrolyte measures (24-hour urinary sodium and potassium). Food frequency questionnaire to establish baseline dietary intake will be obtained at baseline and 12 weeks. **Measure:** Dietary Endpoints **Time Frame:** baseline, 4 weeks **Description:** Mechanism-related endpoints will include changes from baseline to 4 weeks in clinic and 24-hour blood pressure, noninvasive measures of ventricular function and ventricular-arterial coupling, blood/urine measures of neurohormonal activation, oxidative stress, and systemic inflammation, blood volume measurements (subset n=20), and peripheral blood mononuclear cell (PBMC) RNA profiling (subset n=20) **Measure:** Mechanism-related endpoints **Time Frame:** Baseline to 4 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 66 male and female patients aged ≥ 55 years with history of systemic hypertension and acutely decompensated heart failure (ADHF; primary diagnosis for admission or secondary diagnosis after hospitalization for another reason). ADHF will be confirmed by the study physician and defined as a combination of symptoms, signs, and HF-specific medical treatments. Specifically, ADHF will require that all four of the following conditions are met: * ≥1 symptom of HF (dyspnea, fatigue, orthopnea, paroxysmal nocturnal dyspnea) has worsened from baseline * ≥ 2 signs of HF (pulmonary congestion on exam and/or chest X-ray, elevated jugular venous pressure, peripheral edema or rapid weight gain, and/or increased B-type natriuretic peptide (BNP; ≥100 pg/ml) * change in medical treatment specifically targeting HF (diuretics, vasodilators, and/or neurohormonal modulating agents) * no other cause of the patient's symptoms and signs is apparent Exclusion Criteria: * persistent hypotension during hospitalization or excessive risk of hypotension from the study diet as judged by the investigators or systolic BP \<110 on discharge * use of inotropic therapy at hospital discharge, * severe valvular heart disease as the primary etiology of the patient's HF syndrome * uncontrolled hypertension defined as the following criteria for the last 24 hours prior to discharge (systolic BP \>180 mmHg or diastolic BP \>100 mmHg) * having two or more results of a serum potassium \>5.0 mmol/L during hospitalization or history of serum potassium \>6.0 mmol/L, and/or at an excessive risk of hyperkalemia as judged by the investigators * severe renal insufficiency (estimated glomerular filtration rate \<30 ml/min/1.73m\^2 at discharge) * severe anemia (hemoglobin \< 9 gm/dl) * length of stay \<48 hours or \>14 days * co-morbidity with expected survival \< 12 months * active alcohol or substance abuse * history of persistent noncompliance with treatment recommendations as judged by the investigators **Gender Based:** True **Gender Description:** eligibility is based on self-representation of gender identity. **Minimum Age:** 55 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Ann Arbor **Country:** United States **Facility:** Ann Arbor Veterans Affairs Health System **State:** Michigan **Zip:** 48105 **Location 2:** **City:** Ann Arbor **Country:** United States **Facility:** University of Michigan **State:** Michigan **Zip:** 48109 **Location 3:** **City:** New York **Country:** United States **Facility:** Columbia University **State:** New York **Zip:** 10032 #### Overall Officials **Official 1:** **Affiliation:** University of Michigan **Name:** Scott L Hummel, MD, MS **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Hummel SL, DeFranco AC, Skorcz S, Montoye CK, Koelling TM. Recommendation of low-salt diet and short-term outcomes in heart failure with preserved systolic function. Am J Med. 2009 Nov;122(11):1029-36. doi: 10.1016/j.amjmed.2009.04.025. **PMID:** 19854331 **Citation:** Hummel SL, Seymour EM, Brook RD, Kolias TJ, Sheth SS, Rosenblum HR, Wells JM, Weder AB. Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction. Hypertension. 2012 Nov;60(5):1200-6. doi: 10.1161/HYPERTENSIONAHA.112.202705. Epub 2012 Oct 1. **PMID:** 23033371 **Citation:** Hummel SL, Seymour EM, Brook RD, Sheth SS, Ghosh E, Zhu S, Weder AB, Kovacs SJ, Kolias TJ. Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fraction. Circ Heart Fail. 2013 Nov;6(6):1165-71. doi: 10.1161/CIRCHEARTFAILURE.113.000481. Epub 2013 Aug 28. **PMID:** 23985432 **Citation:** Bray GA, Vollmer WM, Sacks FM, Obarzanek E, Svetkey LP, Appel LJ; DASH Collaborative Research Group. A further subgroup analysis of the effects of the DASH diet and three dietary sodium levels on blood pressure: results of the DASH-Sodium Trial. Am J Cardiol. 2004 Jul 15;94(2):222-7. doi: 10.1016/j.amjcard.2004.03.070. Erratum In: Am J Cardiol. 2010 Feb 15;105(4):579. **PMID:** 15246908 **Citation:** Troyer JL, Racine EF, Ngugi GW, McAuley WJ. The effect of home-delivered Dietary Approach to Stop Hypertension (DASH) meals on the diets of older adults with cardiovascular disease. Am J Clin Nutr. 2010 May;91(5):1204-12. doi: 10.3945/ajcn.2009.28780. Epub 2010 Mar 3. **PMID:** 20200258 **Citation:** Racine EF, Lyerly J, Troyer JL, Warren-Findlow J, McAuley WJ. The influence of home-delivered dietary approaches to stop hypertension meals on body mass index, energy intake, and percent of energy needs consumed among older adults with hypertension and/or hyperlipidemia. J Acad Nutr Diet. 2012 Nov;112(11):1755-62. doi: 10.1016/j.jand.2012.06.358. **PMID:** 23102175 **Citation:** Wessler JD, Maurer MS, Hummel SL. Evaluating the safety and efficacy of sodium-restricted/Dietary Approaches to Stop Hypertension diet after acute decompensated heart failure hospitalization: design and rationale for the Geriatric OUt of hospital Randomized MEal Trial in Heart Failure (GOURMET-HF). Am Heart J. 2015 Mar;169(3):342-348.e4. doi: 10.1016/j.ahj.2014.11.021. Epub 2015 Jan 7. **PMID:** 25728723 **Citation:** Bilgen F, Chen P, Poggi A, Wells J, Trumble E, Helmke S, Teruya S, Catalan T, Rosenblum HR, Cornellier ML, Karmally W, Maurer MS, Hummel SL. Insufficient Calorie Intake Worsens Post-Discharge Quality of Life and Increases Readmission Burden in Heart Failure. JACC Heart Fail. 2020 Sep;8(9):756-764. doi: 10.1016/j.jchf.2020.04.004. Epub 2020 Jul 8. **PMID:** 32653445 **Citation:** Hummel SL, Karmally W, Gillespie BW, Helmke S, Teruya S, Wells J, Trumble E, Jimenez O, Marolt C, Wessler JD, Cornellier ML, Maurer MS. Home-Delivered Meals Postdischarge From Heart Failure Hospitalization. Circ Heart Fail. 2018 Aug;11(8):e004886. doi: 10.1161/CIRCHEARTFAILURE.117.004886. **PMID:** 30354562 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01635179 **Brief Title:** Laryngeal View With Videolaryngoscopy **Official Title:** Laryngeal View With Intubation by Videolaryngoscopy With and Without Sellicks Maneuver. #### Organization Study ID Info **ID:** Glo-anaest-2012 #### Organization **Class:** OTHER **Full Name:** Glostrup University Hospital, Copenhagen ### Status Module #### Completion Date **Date:** 2012-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-04-25 **Type:** ESTIMATED **Last Update Submit Date:** 2013-04-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-07 **Type:** ACTUAL #### Start Date **Date:** 2012-04 **Status Verified Date:** 2013-04 #### Study First Post Date **Date:** 2012-07-09 **Type:** ESTIMATED **Study First Submit Date:** 2012-06-19 **Study First Submit QC Date:** 2012-07-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Glostrup University Hospital, Copenhagen #### Responsible Party **Investigator Affiliation:** Glostrup University Hospital, Copenhagen **Investigator Full Name:** Bjorn Arenkiel **Investigator Title:** Principal investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** To prevent bronchial aspiration during induction of anaesthesia it has been a common procedure to perform a cricoid pressure, called Sellicks Maneuver, to occlude esophagus, and thereby prevent aspiration. During the last ten years the efficiency of this maneuver has been discussed, since it probably prolong the intubation time and do not significantly reduces the risk of aspiration. The hypothesis is that Sellicks Maneuver prolong the time of intubation and reduces the view of the laryngeal inlet, during intubation with a videolaryngoscopy. The hypothesis is tested by a double-blinded randomized study where patients is intubated twice, with and without Sellicks Maneuver, in a randomized order. The specific cricoid pressure is blinded to the personal performing the intubation. ### Conditions Module **Conditions:** - Respiratory Aspiration - Hypoxemia **Keywords:** - Videolaryngoscopy - Bronchial Aspiration - Hypoxia ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 50 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** A cricoid pressure of 30 N is done to occlude esophagus under a rapid sequence induction. **Intervention Names:** - Procedure: Cricoid pressure **Label:** Cricoid pressure **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Cricoid pressure **Description:** The patient is intubated twice, once with a cricoid pressure and once with a sham-pressure, when performing a videolaryngoscopy. **Name:** Cricoid pressure **Other Names:** - Sellicks maneuver. - Profylaxis of bronchial aspiration **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** The primary outcome measure is the rate of completed and failed intubations. A intubations is failed when the oxygen saturation is less then 95% or the intubation time is longer then 120 seconds. **Measure:** Completed intubation within 120 seconds **Time Frame:** 120 seconds #### Secondary Outcomes **Description:** The secondary outcome measure is a description of the laryngeal inlet according the the Cormack-Lehan system, and how Sellicks Maneuver alters that view. **Measure:** A description of the laryngeal inlet **Time Frame:** 120 seconds ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ASA 1-2, BMI \< 35, * no indication for rapid sequence induction, * age \> 18, * able to give consent. Exclusion Criteria: * ASA \> 2, * BMI \> 35, * RSI **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Glostrup **Country:** Denmark **Facility:** Glostrup University Hospital **Zip:** 2600 #### Overall Officials **Official 1:** **Affiliation:** GlustrupUH dept of Anaesthesia **Name:** Bjørn Arenkiel, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012818 - Term: Signs and Symptoms, Respiratory - ID: D000012120 - Term: Respiration Disorders - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M27137 - Name: Respiratory Aspiration - Relevance: HIGH - As Found: Respiratory Aspiration - ID: M4185 - Name: Hypoxia - Relevance: HIGH - As Found: Hypoxemia - ID: M15623 - Name: Signs and Symptoms, Respiratory - Relevance: LOW - As Found: Unknown - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000053120 - Term: Respiratory Aspiration - ID: D000000860 - Term: Hypoxia ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT00176579 **Brief Title:** Bone Mineral Density and Cancer Recurrence in Patients With Early Stage Prostate Cancer **Official Title:** Assessing Bone Mineral Density as a Risk Factor for Early Clinically Significant Prostate Cancer #### Organization Study ID Info **ID:** CDR0000539677 #### Organization **Class:** OTHER **Full Name:** Rutgers, The State University of New Jersey #### Secondary ID Infos **ID:** P30CA072720 **Link:** https://reporter.nih.gov/quickSearch/P30CA072720 **Type:** NIH **ID:** CINJ-5004 **ID:** CINJ-4375 ### Status Module #### Completion Date **Date:** 2008-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2011-08-12 **Type:** ESTIMATED **Last Update Submit Date:** 2011-08-11 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-07 **Type:** ACTUAL #### Start Date **Date:** 2003-06 **Status Verified Date:** 2011-08 #### Study First Post Date **Date:** 2005-09-15 **Type:** ESTIMATED **Study First Submit Date:** 2005-09-13 **Study First Submit QC Date:** 2005-09-13 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### Lead Sponsor **Class:** OTHER **Name:** University of Medicine and Dentistry of New Jersey #### Responsible Party **Old Name Title:** Stephen Marcella **Old Organization:** UMDNJ/CINJ ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** RATIONALE: Measuring bone mineral density may help doctors predict whether prostate cancer will come back. It may also help the study of prostate cancer in the future. PURPOSE: This clinical trial is studying whether bone mineral density affects cancer recurrence in patients with early stage prostate cancer. **Detailed Description:** OBJECTIVES: * Determine bone mineral density (BMD) in patients with clinically significant early stage prostate cancer. * Determine whether patients who have a higher level of BMD and have had a radical prostatectomy for cure are less likely to have an early relapse (i.e., less than 3 years) than those patients with a low level of BMD. OUTLINE: This is a case-controlled study followed by a prospective, longitudinal, cohort study. Patients undergo bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry with a densitometer. Posteroanterior measurements of the total hip are also recorded. Patients also undergo blood collection to examine markers that provide evidence of systemic disease. Patients are followed every 6 months for 3 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study. ### Conditions Module **Conditions:** - Osteoporosis - Prostate Cancer **Keywords:** - osteoporosis - stage I prostate cancer ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 27 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Dual x-ray absortiometry by densitometer will be performed to measure bone mineral density **Name:** dual x-ray absorptiometry **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** DXA scan will be done after patient signs consent and eligibilty is confirmed **Measure:** Bone mineral density **Time Frame:** Baseline **Description:** PSA will be measured to look for biochemical recurrence of prostate cancer **Measure:** Prostate Specific Antigen **Time Frame:** Baseline, every 6 months for 3 years ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: * Biopsy-confirmed early stage prostate cancer * Disease localized within the capsule * No evidence of regional or distant spread (i.e., T1-2, N0, M0 disease) * A cohort of patients must have undergone a prior radical prostatectomy * Prostate specific antigen \< 12 ng/mL * Gleason score ≥ 6 PATIENT CHARACTERISTICS: * Creatinine clearance ≤ 2.0 mg/dL * No Paget's disease * No hyperthyroidism or hypothyroidism * No Cushing's disease * No chronic liver disease * No major health problems that would cause a significant reduction in mobility or activities of daily living PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior bisphosphonates, thyroxin, or calcitonin * No prior agents that suppress PSA levels (e.g., finasteride) * No prior androgen or estrogen therapy * More than 12 months since prior glucocorticoids * More than 12 months since prior herbal supplements that are known to lower PSA levels **Maximum Age:** 75 Years **Minimum Age:** 50 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Subjects will be recruited from urologists' offices and the oncological practices of CINJ. This will be done by verbal communication through the office staff and with the distribution of a brochure briefly describing the study. If a person is interested, he will be given information that briefly describes the study and his name will be taken down. A research assistant will call him and set up a meeting, preferably at the same time he is scheduled to see his physician. At that meeting, a research assistant will go over the consent form with him and cover all questions concerning the study. Eligibility (based on history) will also be verified at this meeting. If he wishes to participate, he will be instructed to sign the consent and an appointment for the blood tests and DXA scan will be arranged. ### Contacts Locations Module #### Locations **Location 1:** **City:** New Brunswick **Country:** United States **Facility:** Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School **State:** New Jersey **Zip:** 08903 #### Overall Officials **Official 1:** **Affiliation:** Rutgers Cancer Institute of New Jersey **Name:** Stephen W. Marcella, MD, MPH **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### See Also Links **Label:** Clinical trial summary from Clinicaltrials.gov website **URL:** http://clinicaltrials.gov/ct2/show/NCT00176579 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005834 - Term: Genital Neoplasms, Male - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000005832 - Term: Genital Diseases, Male - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000011469 - Term: Prostatic Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000001851 - Term: Bone Diseases, Metabolic - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M14335 - Name: Prostatic Neoplasms - Relevance: HIGH - As Found: Prostate Cancer - ID: M12947 - Name: Osteoporosis - Relevance: HIGH - As Found: Osteoporosis - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M8946 - Name: Genital Neoplasms, Male - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14333 - Name: Prostatic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M5130 - Name: Bone Diseases, Metabolic - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011471 - Term: Prostatic Neoplasms - ID: D000010024 - Term: Osteoporosis ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05020379 **Brief Title:** The Effects of Erector Spinae Plane Block on Bariatric Surgery. **Official Title:** Investigation of The Effects of The Erector Spinae Plane Block on The Quality Of Recovery After Laparoscopic Bariatric Surgery: A Prospective Randomized Trial #### Organization Study ID Info **ID:** 05-2021/05 #### Organization **Class:** OTHER **Full Name:** Karaman Training and Research Hospital ### Status Module #### Completion Date **Date:** 2022-10-27 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-10-28 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-09-27 **Type:** ACTUAL #### Start Date **Date:** 2021-09-10 **Type:** ACTUAL **Status Verified Date:** 2022-10 #### Study First Post Date **Date:** 2021-08-25 **Type:** ACTUAL **Study First Submit Date:** 2021-08-21 **Study First Submit QC Date:** 2021-08-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Karaman Training and Research Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The erector spinae plane block (ESPB) is a new technique that is increasingly used in the treatment of acute and chronic pain. Bariatric surgery is a surgical treatment method used in the treatment of morbid obesity and related comorbidities. Providing pain control in obese patients is a topic that remains up-to-date. Poorly controlled early postoperative pain impairs quality of recovery, increases the risk of postoperative pulmonary complications, and is a risk factor for the subsequent development of chronic pain. Therefore, optimizing acute postoperative analgesia is a priority in patients undergoing bariatric surgery. The primary aim of this prospective, randomized study is to evaluate the effect of ESPB on quality of recovery with the QoR-40 questionnaire in patients undergoing elective Laparoscopic Bariatric Surgery. **Detailed Description:** In the operating room, all patients will receive standard monitoring, including electrocardiography, non-invasive blood pressure, and peripheral oxygen saturation. Patients in the ESPB group will be placed in a sitting position. A convex probe ultrasound transducer will be placed in a longitudinal parasagittal orientation approximately 3 cm lateral to the spinous process. The needle tip was advanced until it will be located in the inter-fascial plane deep to the erector spinae muscle group and superior to the transverse process. Once in position, bupivacaine 0.25%, 20 ml was injected under ultrasound, guidance. The same procedure will be repeated on the contralateral site. Standard perioperative and postoperative analgesia protocol will be given and postoperative pain levels will be determined by Numerical Rating Scale (NRS). NRS scores for pain and postoperative opioid consumption will be recorded on the 15th,30th minute, 1st, 2nd, 12th, 24th hour, 2nd day. Quality of recovery-40 (QoR-40) scores will be given on the ward, at postoperative 24th hour, 3rd and 7th day ( the 3rd and 7th-day scores will be calculated after telephone interview if the patient will be discharged from the hospital). ### Conditions Module **Conditions:** - Laparoscopic Bariatric Surgery **Keywords:** - Barıatrıc Surgery. - Erector spinae block - Quality of recovery (QoR-40) ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomized Intervention Model: Parallel Assignment ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 80 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The patients in Group N will not receive any intervention. Patients will receive standard multimodal analgesia comprising paracetamol, tenoxicam, and tramadol. The pain intensity will be evaluated with the 0-10 Numeric Rating Scale (NRS). NRS are the simple and most commonly used scales.11 The numerical scale is most commonly 0 to 10, with 0 being "no pain" and 10 being "the worst pain imaginable." **Intervention Names:** - Procedure: Perioperative and postoperative multimodal analgesia **Label:** Group N **Type:** SHAM_COMPARATOR #### Arm Group 2 **Description:** The patients in the group ESPB will be placed in sitting pozition. A convex probe ultrasound transducer will be place in a longitudinal parasagittal orientation about 3 cm lateral to spinous process. Local anesthetic (20 ml 0.25% bupivacaine) will be injected bilaterally into the fascial plane on the deep aspect of erector spinae muscle. Standard perioperative and postoperative analgesia protocol will be given and postoperative pain levels will be determined by Numerical rating scale (NRS) **Intervention Names:** - Procedure: Perioperative and postoperative multimodal analgesia - Procedure: ESP Block **Label:** Group ESPB **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Group ESPB - Group N **Description:** Patients will receive standard multimodal analgesia comprising paracetamol, tenoxicam, and tramadol. The pain intensity during rest and motion will be evaluated with the 0-10 Numeric Rating Scale (NRS). NRS scores for pain and postoperative opioid consumption will be evaluated at 15th and 30th minutes, 1st, 2nd, 6th, 12th, 24th hours, 2nd day. **Name:** Perioperative and postoperative multimodal analgesia **Other Names:** - Global Quality of Recovery-40 score - Standard Pain Follow up **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Group ESPB **Description:** Patients in the ESPB group will be placed in a sitting position. A convex probe ultrasound transducer will be placed in a longitudinal parasagittal orientation approximately 3 cm lateral to the spinous process. Local anesthetic (20 ml 0.25% bupivacaine) will be injected bilaterally into the fascial plane on the deep face of the erector spinae muscle. Standard perioperative and postoperative analgesia protocol will be given and postoperative pain levels will be determined by Numerical Rating Scale (NRS). NRS scores for pain and postoperative opioid consumption will be evaluated at 15th and 30th minutes, 1st, 2nd, 6th, 12th, 24th hours, 2nd day. **Name:** ESP Block **Other Names:** - Global Quality of Recovery-40 score - Standard Pain Follow up **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** QoR-40, a 40-item questionnaire that provides a global score and subscores across five dimensions: patient support, comfort, emotions, physical independence, and pain. Each item is rated on a scale of 1-5, providing a minimum score of 40 and maximum of 200. The increase in scores show high quality of recovery. **Measure:** Quality of Recovery (QoR-40) score **Time Frame:** postoperative 24th hour #### Secondary Outcomes **Description:** NRS use numbers to rate pain from 0 (no pain) to 10 (worst pain). Postoperative pain levels will be determined by Numeric Rating Scale (NRS) system **Measure:** Postoperative pain: numeric rating scale (NRS) **Time Frame:** Postoperative 48 hour **Description:** Total opioid consumption at the postoperative period **Measure:** Analgesic consumption **Time Frame:** Postoperative 48 hour **Description:** Rate of side-effect occurrences (such as rate of vomiting,nausea,dizziness) **Measure:** Side effects **Time Frame:** 24 hours **Description:** Evaluation of the level of sedation in patients with a 4-point scale (0=wake, 1=sleepy, easy to verbally arouse, 2=drowsy, 3=does not open their eyes to verbal commands). **Measure:** Sedation score **Time Frame:** Postoperative 48 hour **Description:** The time after surgery to the mobilization of the patient **Measure:** mobilization time **Time Frame:** Postoperative 24 hour **Description:** QoR-40, a 40-item questionnaire that provides a global score and subscores across five dimensions: patient support, comfort, emotions, physical independence, and pain. Each item is rated on a scale of 1-5, providing a minimum score of 40 and maximum of 200. The increase in scores show high quality of recovery. **Measure:** Quality of Recovery (QoR-40) score **Time Frame:** Postoperative 3rd and 7th days **Description:** Postoperative complications will be identified by visiting patients every day or alternate day during their in hospital course, suplemented by patients medical records using our hospital's electronic patient record database. We will use the Claviene Dindo Classification system from which CC is derived. We defined a postoperative complication as any deviation from the ideal postoperative course, not inherent in the procedure itself and does not constitute a failure to cure. CCI scores willbe calculated using the online CCI calculator. **Measure:** Postoperative complications **Time Frame:** Postoperative 30 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Scheduled for elective laparoscopic bariatric surgery Exclusion Criteria: * a history of allergy to local anesthetics * known coagulation disorders * infection near the puncture site * Chronic opioid intake * Patient with psychiatric disorders * Can not communicate in Turkish **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Karaman **Country:** Turkey **Facility:** Karaman Training and Research Hospital **Zip:** 70200 #### Overall Officials **Official 1:** **Affiliation:** Karaman Training and Research Hospital **Name:** Betul Basaran, MD, DESA **Role:** STUDY_DIRECTOR ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M5315 - Name: Bupivacaine - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown - ID: M4033 - Name: Analgesics, Opioid - Relevance: LOW - As Found: Unknown - ID: M16901 - Name: Tramadol - Relevance: LOW - As Found: Unknown - ID: M244991 - Name: Tenoxicam - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05987579 **Brief Title:** Surgical Treatment of Stage T3 Squamous Cell Carcinomas of the Scalp **Official Title:** Surgical Treatment of Stage T3 Squamous Cell Carcinomas of the Scalp #### Organization Study ID Info **ID:** 2021-2706 #### Organization **Class:** OTHER **Full Name:** Maastricht University Medical Center ### Status Module #### Completion Date **Date:** 2024-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-19 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-18 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2021-05-03 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2023-08-14 **Type:** ACTUAL **Study First Submit Date:** 2023-07-20 **Study First Submit QC Date:** 2023-08-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Maastricht University Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study examines tumor- en surgical characteristics of stage T3 cutaneous squamous cell carcinomas on the scalp, diagnosed between 2010 and 2018. Histological data and patient- and tumor characteristics were collected. **Detailed Description:** Cutaneous squamous cell carcinoma is the second most common type of non-melanoma skin cancer, following basal cell carcinoma. Following the American Joint Committee on Cancer Tumour, Node and Metastasis (TNM) Classification of Malignant Tumors staging system (TNM8), T3 cutaneous squamous cell carcinomas comprise an interesting group, especially on the scalp, because of the thin subcutaneous fat layer. According to the TNM8 criteria, T3 include all cutaneous squamous cel carcinomas with greatest tumor dimension ≥4cm, tumors with minimal bone erosion or perineural growth (defined as involvement of the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1mm or larger in caliber or showing clinical or radiographic involvement of nerves without invasion of the skull base) or with deep invasion. Deep invasion is defined as invasion deeper than the subcutaneous fat or a tumor thickness \>6mm. The scalp has a natural anatomical and oncological barrier for extension in depth known as the epicranial aponeurosis, also called the galea aponeurotica. This retrospective study, examines the tumor- en surgical characteristics of these stage T3 cutaneous squamous cell carcinomas on the scalp. ### Conditions Module **Conditions:** - Squamous Cell Carcinoma - Surgery - Cancer Head Neck ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 104 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Choice of treatment, complications, reconstruction types **Measure:** Surgical characteristics **Time Frame:** Between 2010-2017 **Description:** Histological data on invasion depth, tumor differentiation **Measure:** Tumor characteristics **Time Frame:** Between 2010-2017 **Description:** Risk factors, comorbidities **Measure:** Patients characteristics **Time Frame:** Between 2010-2017 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * stage T3 cutaneous squamous cell carcinoma of the scalp (histologically proven) * surgical treatment or radiotherapy treatment Exclusion Criteria: * metastasis by diagnosis * stage T1/T2/T4 **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Data from patients are collected retrospectively using data from the Pathological Anatomical National Automated Archive (PALGA) of the MUMC+ between 2010 - 2018. The TNM staging of all cutaneous squamous cell carcinomas in the research period was reassessed and classified following the TNM 8 criteria. ### Contacts Locations Module #### Locations **Location 1:** **City:** Maastricht **Country:** Netherlands **Facility:** Ellen Oyen #### Overall Officials **Official 1:** **Affiliation:** Maastricht UMC+ **Name:** Nicole Kelleners-Smeets, dr. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017 Mar;67(2):93-99. doi: 10.3322/caac.21388. Epub 2017 Jan 17. **PMID:** 28094848 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000018307 - Term: Neoplasms, Squamous Cell - ID: D000009371 - Term: Neoplasms by Site ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: HIGH - As Found: Cancer Head Neck - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: HIGH - As Found: Squamous Cell Carcinoma - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M20451 - Name: Neoplasms, Squamous Cell - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000002294 - Term: Carcinoma, Squamous Cell - ID: D000006258 - Term: Head and Neck Neoplasms ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02520479 **Brief Title:** "Sandwich" Chemotherapy With Radiotherapy in Newly Diagnosed, Stage IE to IIE, ENKTL **Official Title:** Phase 2 Trial of "Sandwich" Pegaspargase-CHOP Chemotherapy With Radiotherapy in Newly Diagnosed, Stage IE to IIE, Nasal Type, Extranodal Natural Killer/T-cell Lymphoma #### Organization Study ID Info **ID:** NK-SYSUCC #### Organization **Class:** OTHER **Full Name:** Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2018-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-05-09 **Type:** ACTUAL **Last Update Submit Date:** 2018-05-08 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2017-12 **Type:** ACTUAL #### Start Date **Date:** 2013-06 **Status Verified Date:** 2016-10 #### Study First Post Date **Date:** 2015-08-11 **Type:** ESTIMATED **Study First Submit Date:** 2015-08-04 **Study First Submit QC Date:** 2015-08-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Sun Yat-sen University #### Responsible Party **Investigator Affiliation:** Sun Yat-sen University **Investigator Full Name:** wanghua **Investigator Title:** professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** A phase 2 study was conducted of "sandwich" protocols, with earlier RT after an initial 2 of P-CHOP (Pegaspargase, cyclophosphamide,vincristine, doxorubicin and dexamethasone ), followed by further two "consolidation" cycles,to explore the appropriate mode of combined modality therapy (CMT) in early stage ENKTL. **Detailed Description:** The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined.We conducted a prospective phase II study of "Sandwich" Pegaspargase, cyclophosphamide,vincristine, doxorubicin and dexamethasone (P-CHOP) regimen in combination with radiotherapy.The "sandwich" protocols, refer to earlier RT after an initial 2 cycles of P-CHOP followed by further two "consolidation" cycles. ### Conditions Module **Conditions:** - Treatment Refusal **Keywords:** - extranodal natural killer/T-cell lymphoma - nasal type - radiotherapy - chemotherapy ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** sandwich protocols: Patients with newly diagnosed ENKTL is given 2 cycles of P-CHOP\[cyclophosphamide(CTX), 750 mg/m2 day 1; vincristine(VCR), 1.4 mg/m2 day 1 (maximal dose 2 mg),adriamycin(ADM) 50 mg/m2 day 1; dexamethasone(DXM) 10 mg days 1-8; Pegaspargase 2500 international unit day 1\] before radiotherapy(RT) and then two "consolidation" cycles after RT. **Intervention Names:** - Drug: P-CHOP - Radiation: Radiotherapy **Label:** sandwich protocols **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - sandwich protocols **Description:** Two cycles of P-CHOP:cyclophosphamide, 750 mg/m2 day 1; vincristine,(maximal dose 2 mg),adriamycin , 50 mg/m2 day 1; dexamethasone,10mg days 1-8; Pegaspargase, 2500IU/m2 day 1 are given before radiotherapy **Name:** P-CHOP **Other Names:** - CTX, VCR, ADM , DXM, Pegaspargase **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - sandwich protocols **Description:** Radiotherapy was scheduled after 2 cycles of P-CHOPregimen. Involved field radiotherapy(IFRT) is delivered using 6-Million electron Volts linear accelerator using 3-dimensional conformable treatment planning. The IFRT dose was 56 grays (Gy) in 28 fractions. **Name:** Radiotherapy **Other Names:** - radiotherapy after induction chemotherapy **Type:** RADIATION #### Intervention 3 **Arm Group Labels:** - sandwich protocols **Description:** Two "consolidation" cycles of P-CHOP are given after radiotherapy **Name:** P-CHOP **Other Names:** - CTX, VCR, ADM , DXM, Pegaspargase **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The criteria for the efficacy evaluation (complete remission) of the regimen is according to the following article. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244 **Measure:** complete remission rate **Time Frame:** every 4 weeks,up to completion of treatment(approximately 6 months) #### Secondary Outcomes **Description:** time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first **Measure:** progression free survival **Time Frame:** up to end of follow-up-phase (approximately 3 years) **Description:** time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first. **Measure:** overall survival **Time Frame:** up to end of follow-up-phase (approximately 3 years) **Description:** including hematological safety and non-hematological safety. All the adverse events will be classified according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) **Measure:** Hematological and non-hematological safety as a measure of adverse events according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) **Time Frame:** up to end of follow-up-phase (approximately 3 years) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * newly diagnosed ENKTL * age:18-69years * Ann Arbor stage IE,or stage IIE with cervical lymph node involvement * at lease one measurable lesion * receive no chemotherapy or radiotherapy before * Eastern CooperativeOncology Group performance status of 0 to 2. * Adequate hematologic function (eg, white blood cell ≥ 3×10e9/l,neutrophils count ≥1.5×10e9/L, and platelet count≥ 100×10e9/L),renal function (eg, serum creatinine≤1.5 mg/dL and creatinine clearance ≥50 mL minute), and hepatic function (e.g, total bilirubin≤ 2 times the upper limit of normal and aspartate and alanine transaminase levels ≤ 3 times the upper limit of normal) Exclusion Criteria: * mismatch the inclusion criteria * systematic central nervous system involvement * previous or concomitant malignancies and any coexisting medical problems that could cause poor compliance with the study protocol. * primary lesion not from the upper respiratory **Maximum Age:** 69 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Guangzhou **Country:** China **Facility:** Sun Yat-sen University Cancer Center **State:** Guangdong **Zip:** 510060 #### Overall Officials **Official 1:** **Affiliation:** Clinical Research Center **Name:** minghuang hong, MD. **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: M18829 - Name: Lymphoma, T-Cell - Relevance: LOW - As Found: Unknown - ID: M18833 - Name: Lymphoma, T-Cell, Peripheral - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown - ID: T4496 - Name: Peripheral T-cell Lymphoma - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: AnEm - Name: Antiemetics - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ARhu - Name: Antirheumatic Agents ### Intervention Browse Module - Browse Leaves - ID: M7102 - Name: Dexamethasone - Relevance: LOW - As Found: Unknown - ID: M6727 - Name: Cyclophosphamide - Relevance: LOW - As Found: Unknown - ID: M17495 - Name: Vincristine - Relevance: LOW - As Found: Unknown - ID: M235549 - Name: Dexamethasone acetate - Relevance: LOW - As Found: Unknown - ID: M251156 - Name: Pegaspargase - Relevance: HIGH - As Found: Induction therapy - ID: M4522 - Name: Asparaginase - Relevance: HIGH - As Found: Induction therapy ### Intervention Browse Module - Meshes - ID: C000042705 - Term: Pegaspargase - ID: D000001215 - Term: Asparaginase ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03967379 **Brief Title:** Multimodal Mobile Intervention Application (App) to Address Sexual Dysfunction in Hematopoietic Stem Cell Transplant Survivors **Official Title:** Multimodal Mobile Intervention Application (App) to Address Sexual Dysfunction in Hematopoietic Stem Cell Transplant Survivors #### Organization Study ID Info **ID:** 19-104 #### Organization **Class:** OTHER **Full Name:** Massachusetts General Hospital ### Status Module #### Completion Date **Date:** 2024-01-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-27 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-23 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-01-01 **Type:** ACTUAL #### Start Date **Date:** 2019-02-01 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2019-05-30 **Type:** ACTUAL **Study First Submit Date:** 2019-05-27 **Study First Submit QC Date:** 2019-05-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Massachusetts General Hospital #### Responsible Party **Investigator Affiliation:** Massachusetts General Hospital **Investigator Full Name:** El-Jawahri, Areej,M.D. **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This research study is being done to evaluate whether the use of a mobile app can help transplant survivors experiencing sexual health problems. **Detailed Description:** Frequently survivors of stem cell transplantation report significant problems with their sexual function that impacts their quality of life, mood, and their intimacy and relationship with their partners. These issues can be very distressing to patients and their loved ones. The study doctors want to know if the use of a mobile app intervention focused on improving sexual function may improve participants overall care. ### Conditions Module **Conditions:** - Other Cancer **Keywords:** - Other Cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** * Patients will received enhanced standard care in addition to access to the sexual health mobile app. * The app will also prompt patients to engage their partners with specific exercises. **Intervention Names:** - Behavioral: Mobile App + enhanced standard care - Other: Enhanced Standard Care **Label:** Mobile app plus enhanced standard care **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** * Patients will receive Enhanced Standard Care * Patients will meet with a transplant clinician for a brief medical examination to assess the need for medications for erectile dysfunction, vaginal atrophy, or vulvovaginal GVHD * Patients will not have access to the sexual health mobile app **Intervention Names:** - Other: Enhanced Standard Care **Label:** Enhanced Standard Care **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Mobile app plus enhanced standard care **Description:** An intervention to help address sexual dysfunction among HCT survivors **Name:** Mobile App + enhanced standard care **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Enhanced Standard Care - Mobile app plus enhanced standard care **Description:** Standard of care administered by the institution **Name:** Enhanced Standard Care **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** feasibility will be defined if at least 60% of eligible patients enroll and engage with at least 70% of the intervention modules **Measure:** To assess the feasibility of the intervention **Time Frame:** 2 years #### Secondary Outcomes **Description:** patient-reported global satisfaction using the PROMIS Sexual Function and Satisfaction Measure. Higher scores indicate better global satisfaction with sex (there is a raw and T score. T score range 0-100) **Measure:** Compare patient-reported global satisfaction with sex (PROMIS Sexual Function and Satisfaction Measure) between the study groups **Time Frame:** 8 and 12 weeks **Description:** compare patient-reported interest in sexual activity using the PROMIS Sexual Function and Satisfaction Measure - Interest in Sexual Activity Domain). higher score indicate better interest in sex (there is a raw and T score, T score range 0-100) **Measure:** Compare patient-reported interest in sexual activity (PROMIS Sexual Function and Satisfaction Measure - Interest in sexual activity domain) between the study groups **Time Frame:** 8 and 12 weeks **Description:** compare patient-reported orgasm using the PROMIS Sexual Function and Satisfaction Measure - Orgasm Domain). higher score indicate better orgasm (there is a raw and t-score, t-score range 0-100) **Measure:** Compare patient-reported orgasm (PROMIS Sexual Function and Satisfaction Measure - Orgasm domain) between the study groups **Time Frame:** 8 and 12 weeks **Description:** for males: compare patient-reported erectile function using the PROMIS Sexual Function and Satisfaction Measure - Erectile Function Domain). higher score indicate better erectile function (there is a raw and t-score, T-score range 0-100) **Measure:** For males: compare patient-reported erectile function (PROMIS Sexual Function and Satisfaction Measure - Erectile function domain) between the study groups **Time Frame:** 8 and 12 weeks **Description:** For females: compare patient-reported vaginal comfort and lubrication using the PROMIS Sexual Function and Satisfaction Measure- Lubrication and Vaginal Comfort Domain). higher score indicate better lubrication and vagina comfort (there is a raw and T-score, T-score range 0-100) **Measure:** For females: compare patient-reported lubrication and vaginal comfort (PROMIS Sexual Function and Satisfaction Measure - lubrication and vaginal comfort domains) between the study groups **Time Frame:** 8 and 12 weeks **Description:** compare patient-reported quality of life using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). higher score indicate better quality of life (range 0-196) **Measure:** Compare patient reported quality of life (FACT-BMT) between the study groups **Time Frame:** 8 and 12 weeks **Description:** compare patient-reported depression symptoms using Hospital Anxiety and Depression Scale (HADS-Depression). higher subscale score indicate worse depression symptoms (range 0-21) **Measure:** Compare patient reported depression symptoms (HADS-depression) between the two study groups **Time Frame:** 8 and 12 weeks **Description:** compare patient-reported depression symptoms using Hospital Anxiety and Depression Scale (HADS-Anxiety). higher subscale score indicate worse anxiety symptoms (range 0-21) **Measure:** Compare patient reported anxiety symptoms (HADS-anxiety) between the two study groups **Time Frame:** 8 and 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients (≥18 years) who underwent an autologous or allogeneic HCT at least 3 months prior to study enrollment. * Ability to speak English or able to complete questionnaires with assistance required from an interpreter or family member. * Positive screen for sexual dysfunction that is causing distress based on the NCCN survivorship guidelines Exclusion Criteria: * Recurrent disease requiring treatment * Significant uncontrolled psychiatric disorder (psychotic disorder, bipolar disorder, major depression) or other co-morbid disease (dementia, cognitive impairment), which the treating clinician believes prohibits the ability to participate in study procedures. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Massachusetts General Hospital Cancer Center **State:** Massachusetts **Zip:** 02114 #### Overall Officials **Official 1:** **Affiliation:** Massachusetts General Hospital **Name:** Areej El-Jawahri, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email [email protected] BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at [email protected] BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at [email protected] MGH - Contact the Partners Innovations team at http://www.partners.org/innovation **Description:** The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research **Info Types:** - STUDY_PROTOCOL - SAP - ICF **IPD Sharing:** YES **Time Frame:** Data can be shared no earlier than 1 year following the date of publication ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2024-01-01 - Date Unknown: Unknown #### Event: RESET - Date: 2024-01-22 - Date Unknown: Unknown ## Derived Section ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2024-01-01 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2024-01-01 - Reset Date: 2024-01-22 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - MCP Release N: Unknown - Release Date: 2024-02-06 - Reset Date: Unknown - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03703479 **Acronym:** A-PRF **Brief Title:** Effect of A-PRF After Removal of Wisdom Teeth **Official Title:** The Effect of Advanced Platelet Rich Fibrin in Alveolar Defect After Removal of Bilateral Mandibular Third Molar #### Organization Study ID Info **ID:** 085-10-17 #### Organization **Class:** OTHER **Full Name:** King Abdulaziz University ### Status Module #### Completion Date **Date:** 2019-03-24 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-03-28 **Type:** ACTUAL **Last Update Submit Date:** 2019-03-26 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-02-20 **Type:** ACTUAL #### Start Date **Date:** 2018-10-20 **Type:** ACTUAL **Status Verified Date:** 2019-03 #### Study First Post Date **Date:** 2018-10-12 **Type:** ACTUAL **Study First Submit Date:** 2018-10-08 **Study First Submit QC Date:** 2018-10-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** King Abdulaziz University #### Responsible Party **Investigator Affiliation:** King Abdulaziz University **Investigator Full Name:** talal zahid **Investigator Title:** Assistant professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** To evaluate the healing effect of advanced platelet-rich fibrin (blood clot charged with growth factors) taken from the patient own blood on the extraction site. **Detailed Description:** This is a randomized double-blind clinical study. A preoperative and radiographic evaluation will be done in order to select the patients. Inclusion criteria are healthy patients above 18 years old with vertical or mesioangular bilateral impacted mandibular third molars. Exclusion criteria are missing second molars or indicated for extraction (un-restorable and remaining roots), patients under immunosuppressant and patients with acute infection. Those who fail to attend for follow-up appointments will be excluded. The probing depth (PD) and clinical attachment level (CAL) distal to the second molar will be measured before each procedure. All patients will undergo bilateral removal of 3rd molar in a single appointment. Envelope flap with distal extension and a full-thickness mucoperiosteal flap will be utilized and the teeth will be removed with elevators. Bone removal will be utilized if needed. Following the extraction, venous blood will be withdrawn to fill 2 tubes of 10mL each (sterile vacuum plain tube for A-PRF™ +). The blood tubes will be spun in the centrifugation machine for 13 minutes at 1300 rpm then it is pressed in PRF Box to form PRF clots which will be placed in one the extraction socket while the other socket will not receive a PRF (control).Randomization will be done using a coin toss. Both extraction cavities will be closed using 3-4 interrupted sutures using 3.0 chromic gut sutures. Postoperatively, all patients will be treated with oral antibiotic amoxicillin 500 mg and non-steroidal anti-inflammatory medications ibuprofen 600mg in case. also, all patients will be instructed to rinse with 0.2 % Chlorhexidine mouthwash for seven days postoperative. On the 7th,15th and 90th days, patients will be asked about pain using visual analog scale (VAS) and whether they have any concern related to extraction socket statuses like halitosis, empty socket, open socket, dehiscence, and infection signs including swelling, pus, or fever. They will also undergo a clinical examination at this visit and the consecutive visits. The following measures will be assessed during each clinical examination: the presence of a pocket distal to the adjacent second molar measuring the pocket depth and clinical attachment level and any signs of infection. Data will be analyzed using statistical software. Analysis of multivariate regression will be used. The healing status will be compared between the graft site and the control site. Results will be interpreted to be statistically significant if they have a P-value of less than 0.05 ### Conditions Module **Conditions:** - Wound Heal ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** spilt mouth design ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 10 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Socket site that will receive A-PRF clot **Intervention Names:** - Other: autologous blood clot made from the patient own clot without any additive **Label:** A-PRF group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** socket site that will not receive any intervention **Label:** control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - A-PRF group **Description:** advanced Platelet-rich fibrin clot is made from venous blood withdrawn from the patient **Name:** autologous blood clot made from the patient own clot without any additive **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Periodontal healing is evaluated based on changes in clinical attachment loss (mm) **Measure:** Clinical Attachment Loss (CAL) (also called Periodontal Attachment Loss) **Time Frame:** At baseline and at follow-up 4 weeks and 12 weeks after extraction #### Secondary Outcomes **Description:** Pain reported by the patient according to the visual analogue scale (VAS) will be evaluated at first follow-up visit, the patient will score the pain suffered at each site on 0-10 scale where 0 = no pain and 10 = sever pain **Measure:** Pain reported by the patient according to the visual analogue scale (VAS) **Time Frame:** 7 days after the extraction ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy patients above 18 years old with mirror image vertical or mesioangular bilateral impacted mandibular third molars Exclusion Criteria: * Missing second molars or indicated for extraction (un-restorable and remaining roots). * Patients under immunosuppressant and patients with acute infection. * Patients who fail to attend for follow-up appointments. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Jeddah **Country:** Saudi Arabia **Facility:** King Abdul Aziz University **State:** Makkah **Zip:** 21589 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Zahid TM, Nadershah M. Effect of Advanced Platelet-rich Fibrin on Wound Healing after Third Molar Extraction: A Split-mouth Randomized Double-blind Study. J Contemp Dent Pract. 2019 Oct 1;20(10):1164-1170. **PMID:** 31883251 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03149679 **Brief Title:** The p53 Colorectal Cancer Trial **Official Title:** Treatment of Patients With Metastatic Colorectal Cancer Harboring TP53 Mutations With Dose-dense Cyclophosphamide - the p53 Colorectal Cancer Trial #### Organization Study ID Info **ID:** 2016/1637 #### Organization **Class:** OTHER **Full Name:** Haukeland University Hospital ### Status Module #### Completion Date **Date:** 2020-08-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-01-22 **Type:** ACTUAL **Last Update Submit Date:** 2021-01-20 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2020-08-07 **Type:** ACTUAL #### Start Date **Date:** 2017-05-09 **Type:** ACTUAL **Status Verified Date:** 2020-02 #### Study First Post Date **Date:** 2017-05-11 **Type:** ACTUAL **Study First Submit Date:** 2017-03-14 **Study First Submit QC Date:** 2017-05-09 **Why Stopped:** The study was discontinued after the first pre-planned interim analysis due to insufficient response rates. ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Haukeland University Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Single center, open labeled, phase 2 clinical trial, where patients with metastatic colorectal cancer are selected for treatment with dose dense Cyclophosphamide every second week based on TP53 mutation status; i.e. only patients with TP53 mutated tumors may be included in the treatment arm. ### Conditions Module **Conditions:** - Colorectal Cancer Metastatic - Colorectal Cancer Stage IV - TP53 Gene Mutation **Keywords:** - Cyclophosphamide - Colorectal Cancer Metastatic - TP53 Gene Mutation ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Single center, open labeled, phase 2 clinical trial, where patients are selected for treatment based on upfront TP53 mutation status; i.e. only patients with TP53 mutated tumors may be included in the single treatment arm. The informed consent, however needs to be signed prior to a biopsy for TP53 mutation analyses; thus, all patients are formally enrolled in the study prior to tissue collection, and the full population tested will be accounted for despite the fact that only patients with TP53 mutated tumors may enter the single treatment arm. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week. **Intervention Names:** - Drug: Cyclophosphamide **Label:** Cyclophosphamide arm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Cyclophosphamide arm **Description:** Chemotherapy **Name:** Cyclophosphamide **Other Names:** - Sendoxan **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Partial response (PR) or complete response (CR) as defined by the RECIST criteria **Measure:** Objective response rate (ORR) **Time Frame:** 4 months #### Secondary Outcomes **Description:** Tissue and blood sampling at baseline and whenever treatment is changed **Measure:** Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined. **Time Frame:** 10 years **Description:** Tissue and blood sampling at baseline and whenever treatment is changed **Measure:** Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups **Time Frame:** 10 years **Description:** Stable disease (SD) \>6 months, PR or CR **Measure:** Clinical benefit rate (CBR) **Time Frame:** 5 years **Description:** Survival analyses **Measure:** Recurrence-free and overall survival, compared to historical data **Time Frame:** All patients will be followed for 5 years or until death to record survival outcome **Description:** Clinical examination and blood samples **Measure:** Safety and tolerability of the study treatment including recording of number of participants with treatment-related adverse events as assessed by CTCAE v4.0 **Time Frame:** Every second week during the treatment period from start of treatment, and thereafter every second month for 5 years or until death ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Metastatic colorectal cancer patients for whom conventional therapy has failed; defined as 2 lines of chemotherapy including oxaliplatin or irinotecan- containing regimens as well as an EGFR inhibitor if applicable. * Tumor lesion suitable for biopsy * Age \>18 years * Clinically or radiologically measurable tumor deposits according to the RECIST criteria * WHO performance status 0-1 * Radiology studies (CT thorax/abdomen/pelvis) and echo cor and ECG must be performed within 28 days prior to registration. * Before patient registration in the trial, written informed consent must be given according to national and local regulations. * Blood test requirements: Neutrophils \> 1.0 e9/L Platelets \> 75 e9/L Bilirubin \< 20 µmol / L. Serum creatinine \< 1.5 x ULN Exclusion Criteria: * Co-morbidity including, but not limited to, impaired renal-, liver or bone marrow function, that based on the assessment of the treating physician, may preclude the use of cyclophosphamide at actual doses. * Known hypersensitivity to the study drug, its metabolites or any excipients in the infusion solution. * Psychological, familial, sociological or geographical condition(s) potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial * Pregnant or lactating patients cannot be included. * Clinical evidence of serious coagulopathy. Prior arterial/venous thrombosis or embolism does not exclude patients from inclusion, unless patient is considered unfit by study oncologist. * Patient not able to give an informed consent or comply with study regulations as deemed by study investigator. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bergen **Country:** Norway **Facility:** Haukeland University Hospital **Zip:** 5021 #### Overall Officials **Official 1:** **Affiliation:** Haukeland University Hospital **Name:** Inger Marie Løes, MD PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007414 - Term: Intestinal Neoplasms - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000003108 - Term: Colonic Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000012002 - Term: Rectal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M17890 - Name: Colorectal Neoplasms - Relevance: HIGH - As Found: Colorectal Cancer - ID: M10448 - Name: Intestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M6336 - Name: Colonic Diseases - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M14844 - Name: Rectal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015179 - Term: Colorectal Neoplasms ### Intervention Browse Module - Ancestors - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018501 - Term: Antirheumatic Agents - ID: D000018906 - Term: Antineoplastic Agents, Alkylating - ID: D000000477 - Term: Alkylating Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000019653 - Term: Myeloablative Agonists ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M6727 - Name: Cyclophosphamide - Relevance: HIGH - As Found: Cycle - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M20942 - Name: Antineoplastic Agents, Alkylating - Relevance: LOW - As Found: Unknown - ID: M3820 - Name: Alkylating Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003520 - Term: Cyclophosphamide ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT00439179 **Acronym:** BrUOG-PA205 **Brief Title:** A Trial of GW572016, Gemcitabine and Oxaliplatin for Metastatic Pancreaticobiliary Cancer Schema **Official Title:** BrUOG-PA-205 A Phase I Trial of GW572016, Gemcitabine and Oxaliplatin for Metastatic Pancreaticobiliary Cancer Schema GSK Study ProtocolGSK #103556 #### Organization Study ID Info **ID:** BrUOG-PA-205 #### Organization **Class:** OTHER **Full Name:** Brown University ### Status Module #### Completion Date **Date:** 2007-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-02-17 **Type:** ACTUAL **Last Update Submit Date:** 2020-02-13 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-12 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-05-05 **Type:** ESTIMATED **Results First Submit Date:** 2013-05-13 **Results First Submit QC Date:** 2014-04-03 #### Start Date **Date:** 2006-07 **Status Verified Date:** 2020-02 #### Study First Post Date **Date:** 2007-02-23 **Type:** ESTIMATED **Study First Submit Date:** 2007-02-22 **Study First Submit QC Date:** 2007-02-22 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Lead Sponsor **Class:** OTHER **Name:** Brown University #### Responsible Party **Investigator Affiliation:** Brown University **Investigator Full Name:** howard safran **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** A Phase I Trial of GW572016, Gemcitabine and Oxaliplatin for Metastatic Pancreaticobiliary Cancer Schema **Detailed Description:** The primary objective of this phase I study is to determine the safety, tolerability and optimal tolerated regimen of GW572016 when combined with gemcitabine and with the combination of gemcitabine and oxaliplatin. Three to six patients will be treated at each dose level to assess toxicity. To better assess the safety at the final dose level in both Stage I and Stage II, the number of patients in the cohort at the Maximum Tolerated Dose for both Stages will be expanded to 10. Therefore approximately 34-37 patients will be treated on this study. Trial finished and no further data will be collected. ### Conditions Module **Conditions:** - Metastatic Pancreatic Cancer **Keywords:** - Pancreatic Cancer ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 27 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Weekly gem + GW572016, 1000mg/day (combination) **Intervention Names:** - Drug: cohort 1 **Label:** Cohort 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Weekly gem + GW572016, 1500 mg/day (combination) **Intervention Names:** - Drug: cohort 2 **Label:** Cohort 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** GEMOX + GW572016 1000 mg/day (combination) **Intervention Names:** - Drug: cohort 3 **Label:** cohort 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** GEMOX + GW572016 1500 mg/day (combination) **Intervention Names:** - Drug: cohort 4 **Label:** cohort 4 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Cohort 1 **Description:** Weekly gem + GW572016, 1000mg/day (combination) **Name:** cohort 1 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Cohort 2 **Description:** Weekly gem + GW572016, 1500 mg/day (combination) **Name:** cohort 2 **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - cohort 3 **Description:** GEMOX + GW572016 1000 mg/day (combination) **Name:** cohort 3 **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - cohort 4 **Description:** GEMOX + GW572016 1500 mg/day (combination) **Name:** cohort 4 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** To determine the safety and tolerability of GW572016 when administered with gemcitabine and the combination of gemcitabine and oxaliplatin in patients with advanced pancreaticobiliary cancers. Numbers below are DLTs **Measure:** Toxicity (Number of Patients Who Experiened DLTs) **Time Frame:** until death, approximately 2 years #### Secondary Outcomes **Description:** To assess clinical activity of GW572016 with gemcitabine and with the combination of gemcitabine and oxaliplatin in patients with advanced pancreaticobiliary cancers. **Measure:** Number of Patients Who Experienced a Partial Response **Time Frame:** every two months until progression ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients are required to have histologically or pathologically confirmed, metastatic or locally advanced adenocarcinoma of the pancreas or biliary tree * No prior systemic chemotherapy for locally advanced or metastatic pancreaticobiliary cancer. No prior EGFR inhibitors. * ECOG performance status 0-2 retain ability to swallow oral medications * Age \> 18, non pregnant. Because no dosing or adverse event data are currently available on the use of GW572016 in patients \<18 years of age, children are excluded from this study. * The effects of GW572016 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female is eligible to enter and participate in the study if she is of: 1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who: * Has had a hysterectomy, * Has had a bilateral oophorectomy (ovariectomy), * Has had a bilateral tubal ligation, or * Is post-menopausal(a demonstration of total cessation of menses for ³1 year). 2. Childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following: * Intrauterine Device (IUD), * Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female. * Complete abstinence from sexual intercourse for two weeks before exposure to investigational products, throughout the clinical trial, and for at least one week after the last dose of investigational product. * Double barrier contraception (condom with spermicidal jelly, foam, suppository, or film; diaphragm with spermicide; or male condom and diaphragm) * Adequate hematologic function: ANC≥1500/ul,platelets≥100,000/ul,hemoglobin 8 * Adequate hepatic function with total bilirubin ≤ 1.5mg/dL and ALT or AST ≤ 2x ULN. (Patients with liver metastases may have AST/ALT less than or equal to 5x upper limit of normal). Patients with elevated bilirubin secondary to biliary obstruction that have subsequently been stented may enter the protocol with a bilirubin of \< 2.0 as long as the bilirubin is falling. * Adequate renal function: (creatinine ≤1.5mg/dL or estimated creatinine clearance greater than 60ml/min calculated by the Cockcroft Formula). * Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution. * No peripheral neuropathy for patients who receive oxaliplatin. * Life expectancy of at least 12 weeks * Signed informed consent Exclusion Criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: * Prior treatment with GW572016 or any EGFR targeting therapies. * Prior treatment with systemic chemotherapy for metastatic pancreaticobiliary cancer. * Evidence of brain metastases or leptomeningeal disease * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Known contraindications to the use of oxaliplatin or gemcitabine. * History of allergy to platinum compounds in patients receiving oxaliplatin. Amendment #2 4/28/05 * The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug. * HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with GW572016 * Participation in any investigational study within 28 days prior to study enrolment * Any major surgery (insertion of a vascular access device is not considered a major surgery), hormonal therapy (other than replacement), chemotherapy or radiotherapy within the last 4 weeks and/or not recovered from prior therapy within the last 4 weeks and/or not recovered from prior therapy. * Pregnant or lactating females are excluded from this study because GW572016 is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GW572016, breastfeeding should be discontinued if the mother is treated with GW572016. * Malabsorption syndrome disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption of GW572016. * Any unresolved bowel obstruction. * The patient has inadequate venous access in the clinical judgment of the investigator or designated clinical staff. * The patient is taking any medication on the prohibited medications list in Section 10.2 Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring INR. If medically appropriate and treatment available, the investigator may also consider switching these patients to LMW heparin, where an interaction with GW572016 is not expected. * Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Providence **Country:** United States **Facility:** Brown University Oncology Research Group **State:** Rhode Island **Zip:** 02903 #### Overall Officials **Official 1:** **Affiliation:** Brown University **Name:** howard Safran, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000010182 - Term: Pancreatic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13110 - Name: Pancreatic Neoplasms - Relevance: HIGH - As Found: Pancreatic Cancer - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M13102 - Name: Pancreatic Diseases - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: T4387 - Name: Pancreatic Cancer - Relevance: HIGH - As Found: Pancreatic Cancer ### Condition Browse Module - Meshes - ID: D000010190 - Term: Pancreatic Neoplasms ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M2985 - Name: Gemcitabine - Relevance: LOW - As Found: Unknown - ID: M1674 - Name: Oxaliplatin - Relevance: LOW - As Found: Unknown - ID: M1778 - Name: Lapatinib - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Cohort 1 **Description:** Cohort 1: Weekly gem + GW572016, 1000mg/day. **ID:** EG000 **Other Num at Risk:** 3 **Serious Number At Risk:** 3 **Title:** Cohort 1 **Group ID:** EG001 **Title:** Cohort 2 **Description:** Cohort 2: Weekly gem + GW572016, 1500 mg/day. **ID:** EG001 **Other Num Affected:** 1 **Other Num at Risk:** 11 **Serious Number At Risk:** 11 **Title:** Cohort 2 **Group ID:** EG002 **Title:** Cohort 3 **Description:** Cohort 3: GEMOX + GW572016 1000 mg/day. **ID:** EG002 **Other Num Affected:** 1 **Other Num at Risk:** 6 **Serious Number At Risk:** 6 **Title:** Cohort 3 **Group ID:** EG003 **Title:** Cohort 4 **Description:** Cohort 4: GEMOX + GW572016 1500 mg/day **ID:** EG003 **Other Num Affected:** 2 **Other Num at Risk:** 5 **Serious Number Affected:** 1 **Serious Number At Risk:** 5 **Title:** Cohort 4 **Frequency Threshold:** 0 #### Other Events **Term:** Diarrhea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** DLT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** anorexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** #### Serious Events **Term:** Gr 3 Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Gr 2 Fever, Gr 1 Chills \& Hyperbillirubinemia **Organ System:** Investigations ##### Stats **Group ID:** EG000 **Num At Risk:** 3 **Group ID:** EG001 **Num At Risk:** 11 **Group ID:** EG002 **Num At Risk:** 6 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 5 **Num Events:** 1 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 3 **Group ID:** BG001 **Value:** 11 **Group ID:** BG002 **Value:** 6 **Group ID:** BG003 **Value:** 5 **Group ID:** BG004 **Value:** 25 **Units:** Participants ### Group **ID:** BG000 **Title:** Cohort 1 **Description:** Cohort 1: Weekly gem + GW572016, 1000mg/day. ### Group **ID:** BG001 **Title:** Cohort 2 **Description:** Cohort 2: Weekly gem + GW572016, 1500 mg/day. ### Group **ID:** BG002 **Title:** Cohort 3 **Description:** Cohort 3: GEMOX + GW572016 1000 mg/day. ### Group **ID:** BG003 **Title:** Cohort 4 **Description:** Cohort 4: GEMOX + GW572016 1500 mg/day ### Group **ID:** BG004 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 3 #### Measurement **Group ID:** BG004 **Value:** 12 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 2 #### Measurement **Group ID:** BG004 **Value:** 13 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 17 **Value:** 58.6 #### Measurement **Group ID:** BG001 **Spread:** 11 **Value:** 66 #### Measurement **Group ID:** BG002 **Spread:** 6 **Value:** 61.5 #### Measurement **Group ID:** BG003 **Spread:** 12 **Value:** 64.2 #### Measurement **Group ID:** BG004 **Spread:** 10.7 **Value:** 63.7 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 3 #### Measurement **Group ID:** BG004 **Value:** 11 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 2 #### Measurement **Group ID:** BG004 **Value:** 14 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 6 #### Measurement **Group ID:** BG003 **Value:** 5 #### Measurement **Group ID:** BG004 **Value:** 25 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants **Population Description:** participant number correlates to all enrolled patients treated on this study as a whole which is the way in which the abstract was written and therefore how these results are entered ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** BrUOG **Phone:** 4018633000 **Title:** Howard Safran, MD ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** To determine the safety and tolerability of GW572016 when administered with gemcitabine and the combination of gemcitabine and oxaliplatin in patients with advanced pancreaticobiliary cancers. Numbers below are DLTs **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** until death, approximately 2 years **Title:** Toxicity (Number of Patients Who Experiened DLTs) **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** Cohort 1: Weekly gem + GW572016, 1000mg/day. **ID:** OG000 **Title:** Cohorts 1 ##### Group **Description:** weekly gem+ GW572016, 1500mg/day **ID:** OG001 **Title:** Cohort 2 ##### Group **Description:** GEMOX+ GW572016 1000mg day **ID:** OG002 **Title:** Cohort 3 ##### Group **Description:** GEMOX+ GW572016 1500mg/day **ID:** OG003 **Title:** Cohort 4 #### Outcome Measure 2 **Description:** To assess clinical activity of GW572016 with gemcitabine and with the combination of gemcitabine and oxaliplatin in patients with advanced pancreaticobiliary cancers. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** every two months until progression **Title:** Number of Patients Who Experienced a Partial Response **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Cohort 1: Weekly gem + GW572016, 1000mg/day. **ID:** OG000 **Title:** Cohorts 1 ##### Group **Description:** Cohort 2: Weekly gem + GW572016, 1500 mg/day. **ID:** OG001 **Title:** Cohort 2 ##### Group **Description:** Cohort 3: GEMOX + GW572016 1000 mg/day. **ID:** OG002 **Title:** Cohort 3 ##### Group **Description:** Cohort 4: GEMOX + GW572016 1500 mg/day **ID:** OG003 **Title:** Cohort 4 ### Participant Flow Module #### Group **Description:** Cohort 1: Weekly gem + GW572016, 1000mg/day. (combination) **ID:** FG000 **Title:** Cohort 1 #### Group **Description:** Cohort 2: Weekly gem + GW572016, 1500 mg/day. (combination) **ID:** FG001 **Title:** Cohort 2 #### Group **Description:** Cohort 3: GEMOX + GW572016 1000 mg/day. (combination) **ID:** FG002 **Title:** Cohort 3 #### Group **Description:** Cohort 4: GEMOX + GW572016 1500 mg/day.(combination) **ID:** FG003 **Title:** Cohort 4 #### Period **Title:** Overall Study ##### Withdraw **Type:** * 1 pt inelig, 1 pt numb not used ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 5 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 11 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 5 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 **Recruitment Details:** Patients with both pancreatic and bilary cancer were enrolled **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT04445779 **Acronym:** PREKARKID-10 **Brief Title:** Q10 Preloading Before Cardiac Surgery for Kidney Failure Reduction **Official Title:** Q10 Preloading Before Cardiac Surgery for Kidney Failure Reduction #### Organization Study ID Info **ID:** 28878529 #### Organization **Class:** OTHER **Full Name:** Clinical Hospital Center, Split ### Status Module #### Completion Date **Date:** 2021-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-07-16 **Type:** ACTUAL **Last Update Submit Date:** 2020-07-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-09 **Type:** ESTIMATED #### Start Date **Date:** 2020-07-15 **Type:** ESTIMATED **Status Verified Date:** 2020-07 #### Study First Post Date **Date:** 2020-06-24 **Type:** ACTUAL **Study First Submit Date:** 2020-06-05 **Study First Submit QC Date:** 2020-06-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Clinical Hospital Center, Split #### Responsible Party **Investigator Affiliation:** Clinical Hospital Center, Split **Investigator Full Name:** Hrvoje Vučemilović **Investigator Title:** Hrvoje Vučemilović, Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Coenzyme Q10 (CoQ10) is an essential molecule in human body. It acts as an antioxidant, a co-factor for energy conversion in mitochondria and has anti-inflammatory effects capable of improving endothelial function. Our goal is to investigate whether CoQ10 is capable to reduce the incidence of acute kidney injury/failure following cardiac surgery. Cardiac surgery is major risk factor for acute kidney injury/failure (AKI/F). ### Conditions Module **Conditions:** - Acute Kidney Injury - Acute Kidney Failure ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will receive per-orally 10 mg/kg of body weight of coenzyme Q10 in the form of Myokinon (PharmaNord, Denmark) in three divided doses. They will receive therapy for at least 10 days before the surgical procedure. **Intervention Names:** - Dietary Supplement: Coenzyme Q10 **Label:** CoQ10 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients will receive per-orally placebo in three divided doses. **Intervention Names:** - Dietary Supplement: Coenzyme Q10 **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - CoQ10 - Placebo **Description:** Patients will receive per-orally 10 mg/kg of body weight of coenzyme Q10 in form of Myokinon (PharmaNord, Denmark) in three divided doses. They will receive therapy for at least 10 days before surgical procedure. **Name:** Coenzyme Q10 **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Increase in serum creatinine as defined by KDIGO stages will be used as indicator of kidney injury. **Measure:** Difference in serum creatinine after cardiac surgery indicating kidney injury. **Time Frame:** 7 days **Description:** Alpha 1 microglobulin is an indicator of kidney tubular damage, measured in urine. **Measure:** Difference in urinary low molekular weight alpha 1 microglobulin as an indicator of kidney tubular injury. **Time Frame:** 3 days **Description:** Urine output less than 0.5 ml/kg/h during 6 hours indicates increased risk of developing AKI. **Measure:** Daily urine output during the 72 hours postoperatively. **Time Frame:** 3 days #### Secondary Outcomes **Description:** Length of stay in intensive care unit will be compared between an intervention and placebo arm of trial. **Measure:** Length of stay in intensive care unit **Time Frame:** 10 days **Description:** Elevated advanced glycation endproducts (AGE) in skin, measured using skin autofluorescence, are reliable predictors of cardiovascular disease and diabetes mellitus. Elevated levels before cardiac surgery should also predict increased risk of intraoperative morbidity, mortality and postoperative complications. **Measure:** Advanced glycation endproducts **Time Frame:** 7 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients scheduled for elective cardiac surgery Exclusion Criteria: * patients receiving high dose vitamin B supplementation (defined as more that 200% of recommended daily allowances) * patients under warfarin therapy * urgent surgery * end stage kidney disease * therapy with multiple nephrotoxic drugs * chronic kidney disease * obstructive uropathy * previous cardiac surgery procedure * alcohol abuse * malignancy * allergy to any ingredient of Myoqinon capsule * patients receiving Myoqinon and fail to demonstrate a significant increase in blood concentration of Q10 * uncontrolled hypertension **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Hrvoje Vučemilović, MD **Phone:** 00385914444032 **Role:** CONTACT #### Locations **Location 1:** **City:** Split **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Hrvoje Vučemilović, MD - **Phone:** 00 385 91 4444 032 - **Role:** CONTACT **Country:** Croatia **Facility:** Clinical Hospital Center Split **State:** Splitsko Dalmatinska Županija **Status:** RECRUITING **Zip:** 21000 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007674 - Term: Kidney Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M28998 - Name: Acute Kidney Injury - Relevance: HIGH - As Found: Acute Kidney Injury - ID: M26718 - Name: Renal Insufficiency - Relevance: HIGH - As Found: Kidney Failure - ID: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000058186 - Term: Acute Kidney Injury - ID: D000051437 - Term: Renal Insufficiency ### Intervention Browse Module - Ancestors - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000014815 - Term: Vitamins ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M271049 - Name: Coenzyme Q10 - Relevance: HIGH - As Found: Micronutrient - ID: M17201 - Name: Ubiquinone - Relevance: HIGH - As Found: Vacuum - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: T383 - Name: Coenzyme Q10 - Relevance: HIGH - As Found: Micronutrient ### Intervention Browse Module - Meshes - ID: D000014451 - Term: Ubiquinone - ID: C000024989 - Term: Coenzyme Q10 ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02330679 **Brief Title:** Prediction of Antidepressant Treatment Response Using Machine Learning Classification Analysis **Official Title:** Prediction of Individual Treatment Response Based on Brain Changes at the Early Phase of Antidepressant Treatment in Major Depressive Disorder Using Machine Learning Classification Analysis #### Organization Study ID Info **ID:** REB 14-0194 #### Organization **Class:** OTHER **Full Name:** University of Calgary ### Status Module #### Completion Date **Date:** 2016-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2015-01-05 **Type:** ESTIMATED **Last Update Submit Date:** 2015-01-02 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2016-12 **Type:** ESTIMATED #### Start Date **Date:** 2014-12 **Status Verified Date:** 2014-12 #### Study First Post Date **Date:** 2015-01-05 **Type:** ESTIMATED **Study First Submit Date:** 2014-12-31 **Study First Submit QC Date:** 2015-01-02 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Alberta #### Lead Sponsor **Class:** OTHER **Name:** University of Calgary #### Responsible Party **Investigator Affiliation:** University of Calgary **Investigator Full Name:** Rajamannar Ramasubbu **Investigator Title:** Associate Prof **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Despite significant advances in pharmacological treatment, the global burden of depression is increasing worldwide. The major challenge in antidepressant treatment is the clinicians' inability to predict the variability in individual response to the treatment. The development of biomarkers to predict treatment outcomes would enable clinician to find the right medication for a particular patient at the early stage of the treatment and thus could reduce prolonged suffering and ineffective protracted treatment. Brain imaging studies that examined brain predictors of treatment response based on group comparisons have limited value in classifying individuals as responders or non-responders. Machine learning classification techniques such as the support vector machine (SVM) method have proven useful in the classification of individual brain image observations into distinct groups or classes. However, studies that have applied the SVM method to structural and functional magnetic resonance scans (fMRI) involved small sample sizes and were confounded by placebo responses. Furthermore, a recent meta-analysis of clinical trials and EEG studies have shown that early clinical responses and brain changes at the early phase of antidepressant treatment may predict later clinical outcomes suggesting that neural markers measured in the early phase of antidepressant treatment may improve predictive accuracy. However, there is no fMRI study to date that has examined the predictive accuracy of data obtained in early phase of the treatment. We have preliminary fMRI data relating to early treatment response that form the basis of this proposed study. The main objective of this study is to use machine learning method to examine the predictive value (sensitivity, specificity, accuracy) of resting state and emotional task-related fMRI data collected at pre-treatment baseline (week 0) and in the early phase of antidepressant treatment (week 2) in the classification of remitters (\< 10 MADRS scores after 12 weeks of treatment) and non-remitters in patients with major depressive disorder (MDD). A secondary objective is to determine which data set (week 0 or week 2) gives the best predictive value. **Detailed Description:** Major depressive disorder (MDD) is a highly prevalent, chronic disabling condition with substantial morbidity and mortality. Depression currently is the fourth leading cause of global burden of disease (DALYs) and disability worldwide, and is expected to be second by 20201. Around one in eight people in Canada will develop depression during their lifetime, with the total cost to the Canadian economy estimated at $51 billion per year2. The costs of treating MDD are high in part due to limitations in effectiveness of antidepressant treatment. Approximately 60% of patients fail to remit to the first antidepressant prescribed3 and the subsequent selection of antidepressants remains a matter of trial and error. Using this trial and error approach, it may take a year or more to find the successful treatment for a patient4,5. The protracted ineffective treatment results in prolonged suffering, substantial morbidity, loss of productivity and an increased burden on patient's family. Brain-based biomarkers could assist in predicting clinical response to treatment intervention and in tailoring treatment for individual patients. The results of previous neuroimaging studies that examined brain markers of treatment response were derived from group averages 6,-9 and have limited predictive value at individual level. Another limitation of these studies is that predictors derived from the pretreatment baseline brain scans could be influenced by many personal (personality, childhood trauma, genotypes) and clinical (course, duration of illness, episodes, symptom clusters, and severity of symptoms and past medication exposure) characteristics which may limit the generalizability. On the other hand, there is growing evidence that the early clinical response within 2 weeks of antidepressant treatment and EEG changes in the first week of treatment can predict later outcomes. Furthermore, early treatment changes in brain function may provide crucial information on the brain's capacity to change with treatment and on the interactive effects between personal/ clinical characteristics and pharmacological factors, which may help differential prediction of treatment responses to two antidepressants. Hence, examining the predictive value of dynamic brain changes during the first two weeks of treatment in individual patients would improve statistical reliability and predictive accuracy and minimize the confounding effect inherent to pretreatment scans. In this study, we propose to investigate the predictive value of resting state and task related fMRI data collected at the pretreatment baseline and 2 weeks after treatment to predict remitters and non-remitters to desvenlafaxine antidepressant treatment at week 12 using machine learning classifier. Desvenlafaxine is a serotonin norepinephrine reuptake inhibitor (SNRI) with proven efficacy, and safety and is easy to administer in single daily dose. It has limited sedative and cognitive side effects such as drowsiness, lack of alertness and poor attention, which may confound early brain changes with treatment. This study will provide brain-based predictive biomarkers that can be tested prospectively in clinical trials and eventually in clinical practice for accuracy. Machine Learning Classification (Support Vector Machine): The support vector machine (SVM) is a computer based analytical technique designed for high dimensional biological data such as fMRI data and provides the best classification of individual observations into distinct groups 38. Diagnostic classification (depression diagnosis and healthy control) and classification of treatment responsiveness (responders and non-responders) have been examined in a clinical population with fMRI data using SVM 39-41. This technique consists of two phases: training phase and testing phase. During the training phase an SVM is trained to develop a decision function or hyperplane that separates the data into two groups according to a class label. In the testing phase, this decision function can be used to predict the class label of a new subject as being a responder or non-responder. The accuracy of prediction by SVM depends on its specificity (identification of true negatives) and sensitivity (identification of true positives). In recent years a few neuroimaging studies have employed SVM to structural and functional MRI data in order to predict the MDD patients who improved with treatment and who did not. Fu et al (2008) showed that applying SVM on emotional task-related fMRI data, 62% of patients who achieved remission (sensitivity) and 75% of patients who did not achieve remission (specificity) following 8 weeks of fluoxetine treatment could be predicted. But these results were not statistically significant due to small sample sizes (remitters =8, non-remitters=10). Similarly, Costafreda et al (2009) applied SVM to pretreatment structural scans and showed prediction with a sensitivity of 88.9 % and a specificity of 88.9% and accuracy of 88.9% in a small sample comprised of 18 patients 40. In a recent study involving 61 MDD patients, SVM analysis of pretreatment white matter data predicted clinical outcome of refractory and non- refractory depression with an accuracy of 65.22%, sensitivity of 56.2% and specificity of 73.91% 41. Although the results of the later study were statistically significant, the low sensitivity and accuracy may limit its clinical use. Moreover, the structural imaging may not be useful to examine predictive value of early treatment changes in the brain function. In summary, there are no studies, to date that have applied SVM to functional data generated from a large sample for use in evaluating predictive accuracy at the individual level. Main objective : Using machine learning method to examine the predictive value (sensitivity, specificity, accuracy) of resting state and emotional task-related fMRI data collected at the pretreatment time (week 0) and at the early phase of antidepressant treatment (week 2) in the classification of remitters and non-remitters in patients with MDD after 12 weeks of treatment. Secondary objective: To compare the predictive value of pretreatment baseline brain activity (week 0) with early treatment brain activity (week 2). Primary hypothesis: By employing a machine learning method to pretreatment and 2 week post-treatment fMRI data, we hypothesize that it is possible to predict with significant accuracy whether an individual patient with MDD could be classified as remitter or non-remitter at the end of 12 weeks of antidepressant treatment. Secondary hypothesis (Exploratory): Based on previous EEG studies and our preliminary data of standard group comparisons showing early treatment response and associated brain changes, we hypothesize that prediction of antidepressant treatment outcome at an individual level, will be better using fMRI data obtained early in treatment (2 weeks) as compared with pretreatment fMRI data. Rationale: The current study is designed to evaluate the predictive value of early brain changes related to antidepressant treatment to classify remitters and non-remitters based on their clinical response at 12 weeks of treatment. Traditionally, the neuroimaging studies have used group comparisons of pretreatment scans for treatment outcome prediction, which has limited clinical value to make predictions at the individual level. Machine learning methods can provide prediction at the individual level, which can be prospectively used in clinical practice. As the meta-analysis of clinical trials indicate that early clinical response is a reliable predictor of later treatment outcome11,12, our study will examine brain scans at both pretreatment and early post-treatment (2 weeks) times. Experimental Design and Procedure: The eligible patients with MDD will enter into a single blind placebo treatment for two weeks. At the end of two weeks of placebo treatment, participants will be considered as placebo responders based on improvement in depression symptoms as measured by the MADRS scale ( \>50% decrease in MADRS scores from the baseline). The placebo responders will be excluded from the study. The end of two weeks of placebo treatment will be considered as week 0 for active treatment. The placebo non-responders who remain eligible with a score of 22 or higher in MADRS will receive desvenlafaxine 50mg/day for 14 days and the dosage will be increased to 100 mg /day at day 15 if the patient does not improve by 20% reduction in MADRS scores and the dosage determined at day 15 will be maintained until the end of 12 weeks. The first fMRI session will be performed at week 0 (pretreatment baseline) and the second session will be performed at the end of week 2 (14 th day). The participants will be assessed clinically at weeks 1,2,4,6,8,10 and 12 using MADRS, 17-item Hamilton Depression (HAM-D) rating Scale46, Hamilton anxiety (HAM-A) rating scale47 and clinical global impression severity of illness scale (CGI-S) and clinical global impression-improvement scale (CGI-I) 48. HAM-A (Hamilton 1959) will be used to rate anxiety symptoms. To evaluate the overall clinical improvement, CGI-S and CGI-I will be given. Quality of life measure (Q-LES-Q) 49 will be given at the baseline (week 0) and at week 12. Adverse effects will be recorded at each visit. MADRS scores at week 12 will be used to determine remitters and non-remitters. Patients who score less than 10 in MADRS at week 12 will be considered as remitters 50. fMRI Scanning Methods The first fMRI session will be performed at week 0 (pretreatment baseline) and the second session will be performed at the end of week 2. Images will be collected using a Discovery MR750 3T MRI system (GE Healthcare, Waukesha, WI, USA) at the Seaman Family MRI Research Centre at Foothills Hospital, Calgary. Anatomical images will include a 3D T1-weighted MPRAGE image (TR=9.2ms; TE= minimum; flip angle=20; FOV=25.6 cm; voxel size=1mm3. Resting state will consist of a 5-min resting-state scan during which the participants will be asked to keep their eyes closed and hold still ( TR=2000ms;TE=30ms;flip angle=75 degrees; FOV=24 cm; matrix size =64x64, number of slices=36; slice thickness=4mm) Two additional functional MRI scans will also be collected while participants perform an emotional stroop task (block design) using the same acquisition parameters as described for the fMRI resting scan. Machine learning Analysis We will use support vector machines (SVMs), as these have been successfully applied to predicting treatment outcomes in MDD from fMRI data. After preprocessing, SVM as implemented in PROBID software package (http://www.brain.map.co.uk/probid.htm) will be used to investigate the accuracy of whole brain resting and task-related Blood Oxygen Level Dependent (BOLD) data in predicting response to antidepressant treatment. Individual brain scans will be treated as points located in a high dimensional space defined by BOLD response values in the preprocessed images. During the training phase, a linear decision boundary in this high dimensional space will be defined by a "hyperplane" that separates the individual scans according to a class label. SVM classifier will be trained by providing examples of the form \<X,C\> where X represents the fMRI data and C represents the class label (C= 1 for remitters, and C = -1 for non-remitters). Once the hyperplane is determined from the training data, it will be used to predict the class label of a test sample. A linear kernel SVM will be used to extract the weight sector as an image (SVM discriminating map). A "leave-one-out" cross validation method will be used to validate the classifier. This procedure involves excluding a single subject from each group and the classifier will be trained using the remaining subjects. The subject pair excluded will be used to test the ability of the classifier to distinguish between remitters and non-remitters. The procedure will be repeated for each subject pair in the sample in order to assess the overall accuracy of SVM. To establish whether the classification accuracy is statistically significant, we will perform permutation testing. This will involve repeating the classification procedure 1000 times with a random permutation of the training group labels and counting the number of permutations that achieve higher sensitivity and specificity than the one observe with the true labels. The p value will be calculated by dividing this number by 1000. Bonferroni correction or false discovery rate will be used to correct for multiple testing. This SVM analysis and permutation testing will be performed on the pretreatment scan and 2-week post-treatment scan separately. The task-related data and resting state data will be analyzed separately. Sample size calculation The sample size calculation for a classification study is based on precision we want to achieve for sensitivity and specificity. The precision refers to the width of the 95% confidence intervals associated with the estimates. To achieve the 95% confidence interval of plus and minus of 0.16 for 85 % sensitivity and 85% specificity, we will need a total sample of 40 subjects. Having a sample size of 40 should achieve statistically significant classification accuracy and clinically meaningful sensitivity and specificity. Accounting a placebo response of 30% and drop out of 10%, we need to recruit a total of 61 subjects for the sample of 40. ### Conditions Module **Conditions:** - Major Depressive Disorder **Keywords:** - Major Depression, Neuroimaging, Desvenlafaxine, Machine learning ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 61 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 2-week single-blind placebo run-in phase followed by a 12-week open-label trial with desvenlafaxine **Intervention Names:** - Drug: Desvenlafaxine - Drug: Placebo **Label:** Desvenlafaxine **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Desvenlafaxine **Description:** The intervention will consist of a 2-week single-blind placebo run-in phase followed by a 12-week open-label trial with desvenlafaxine (a SNRI medication) **Name:** Desvenlafaxine **Other Names:** - Prestiq **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Desvenlafaxine **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The predictive value of brain activity pattern at the baseline and two weeks post treatment to classify remitters and non-remitters at 12 weeks of antidepressant treatment using machine learning classifiers **Measure:** The resting state and emotional task related brain activity pattern at the pretreatment baseline and two weeks post treatment as measured by functional MRI and analyzed by machine learning techniques **Time Frame:** 2 weeks #### Secondary Outcomes **Description:** MADRS scores at week 12 will be used to determine remitters and non-remitters. Patients who score less than 10 in MADRS at week 12 will be considered as remitters. **Measure:** The clinical response to antidepressant treatment as measured by Montgomery-Asberg Depression Rating (MADRS) scale. **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Acute episode of major depressive disorder of unipolar subtype and a score of 22 or higher in the Montgomery-Asberg Depression Rating (MADRS) scale 2. Free of psychotropic medication for a minimum of 4 weeks at recruitment Exclusion Criteria: 1. Axis I disorders such as bipolar disorder, anxiety disorders, psychosis or history of substance abuse within 6 months of study participation 2. severe borderline personality disorder 3. severe medical and neurological disorders 4. severe suicidal patients 5. failure to respond to three trials of antidepressant medication 6. subjects who arecontraindicated for MRI. Subjects considered unsuitable for MRI include those with cardiac pacemakers, neural pacemakers, surgical clips, metal implants, cochlear implants, or metal objects or particles in their body. Pregnancy, a history of claustrophobia, weight over 250 lb, or uncorrected vision will also be causes of exclusion for participation. **Maximum Age:** 55 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Rajamannar Ramasubbu, MD, FRCP(C) **Phone:** 403-210-6890 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Darren Clark, PhD **Phone:** 403-210-6353 **Role:** CONTACT #### Locations **Location 1:** **City:** Calgary **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Rajamannar Ramasubbu, MD, FRCP(C) - **Phone:** 403-210-6890 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Darren Clark, PhD - **Phone:** 403-210-6353 - **Role:** CONTACT ***Contact 3:*** - **Name:** Rajamannar Ramasubbu, MD, FRCP(C) - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** University of Calgary, TRW Building, Foothills Hospital Campus **State:** Alberta **Status:** RECRUITING **Zip:** T2N4Z6 **Location 2:** **City:** Calgary **Contacts:** ***Contact 1:*** - **Name:** Rajamannar Ramasubbu, MD, FRCP(C) - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** University of Calgary: Foothills Hospital **State:** Alberta **Status:** RECRUITING **Zip:** T2N4Z6 #### Overall Officials **Official 1:** **Affiliation:** University of Calgary **Name:** Rajamannar Ramasubbu, MD, FRCP(C) **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000001526 - Term: Behavioral Symptoms ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depressive Disorder - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depressive Disorder - ID: M7060 - Name: Depressive Disorder, Major - Relevance: HIGH - As Found: Major Depressive Disorder - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003866 - Term: Depressive Disorder - ID: D000003863 - Term: Depression - ID: D000003865 - Term: Depressive Disorder, Major ### Intervention Browse Module - Ancestors - ID: D000068760 - Term: Serotonin and Noradrenaline Reuptake Inhibitors - ID: D000014179 - Term: Neurotransmitter Uptake Inhibitors - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000928 - Term: Antidepressive Agents - ID: D000011619 - Term: Psychotropic Drugs ### Intervention Browse Module - Browse Branches - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: VaCoAg - Name: Vasoconstrictor Agents ### Intervention Browse Module - Browse Leaves - ID: M4247 - Name: Antidepressive Agents - Relevance: LOW - As Found: Unknown - ID: M437 - Name: Desvenlafaxine Succinate - Relevance: HIGH - As Found: Confirmed by - ID: M12575 - Name: Norepinephrine - Relevance: LOW - As Found: Unknown - ID: M15512 - Name: Serotonin - Relevance: LOW - As Found: Unknown - ID: M305 - Name: Serotonin and Noradrenaline Reuptake Inhibitors - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069468 - Term: Desvenlafaxine Succinate ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04742179 **Acronym:** CLIMACTIONS **Brief Title:** Fighting Climate Change: Urban Greennes, Active Mobility and Health Co-benefits. **Official Title:** Fighting Climate Change: Urban Greennes, Active Mobility and Health Co-benefits. #### Organization Study ID Info **ID:** 11/2020 #### Organization **Class:** OTHER **Full Name:** Istituto per la Ricerca e l'Innovazione Biomedica ### Status Module #### Completion Date **Date:** 2022-05-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-12-23 **Type:** ACTUAL **Last Update Submit Date:** 2022-12-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-05-11 **Type:** ACTUAL #### Start Date **Date:** 2022-01-11 **Type:** ACTUAL **Status Verified Date:** 2022-12 #### Study First Post Date **Date:** 2021-02-05 **Type:** ACTUAL **Study First Submit Date:** 2021-01-28 **Study First Submit QC Date:** 2021-02-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Istituto per la Ricerca e l'Innovazione Biomedica #### Responsible Party **Investigator Affiliation:** Istituto per la Ricerca e l'Innovazione Biomedica **Investigator Full Name:** Stefania La Grutta, MD **Investigator Title:** Research Manager **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This is a prospective, non-randomized, controlled, interventional study aiming to assess, in a primary school in the city of Palermo, the health effects of a maintenance and care intervention of the school's green areas. All children of the third, fourth and fifth classes of two school complexes of the same primary school will be selected. One complex will undergo maintenance and care of the green areas and gardens inside the school. The other complex will serve as a control group and will not undergo any intervention. The study will involve three phases. 1. During the first phase (prior to the intervention) respiratory and allergic symptoms will be assessed through a standardized questionnaire to be administered to students, parents and teachers in both the school complexes. 2. During the second phase, the maintenance and care intervention plan will be implemented in the experimental complex. 3. During the third phase, 1 week after the maintenance intervention, respiratory and allergic symptoms will be re-assessed through a standardized questionnaire to be administered to the same students, parents and teachers in both the school complexes. ### Conditions Module **Conditions:** - Respiratory and Allergic Symptoms ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 175 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The children belonging to the classes of the school complex undergoing the maintenance intervention. **Intervention Names:** - Other: Manteinance and care intervention on the green areas. **Label:** Experimental group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The children belonging to the classes of the school complex that will not undergo the maintenance intervention. **Label:** Control group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental group **Description:** Manteinance and care intervention on the green areas. **Name:** Manteinance and care intervention on the green areas. **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Presence of asthma symptoms before the maintenance intervention **Measure:** Asthma symptoms at baseline **Time Frame:** Before the maintenance intervention **Description:** Presence of rhinitis symptoms before the maintenance intervention **Measure:** Rhinitis symptoms at baseline **Time Frame:** Before the maintenance intervention **Description:** Presence of conjunctivitis symptoms before the maintenance intervention **Measure:** Conjunctivitis symptoms at baseline **Time Frame:** Before the maintenance intervention **Description:** Presence of asthma symptoms after the maintenance intervention **Measure:** Asthma symptoms at follow-up **Time Frame:** 7 days after the maintenance intervention **Description:** Presence of rhinitis symptoms after the maintenance intervention **Measure:** Rhinitis symptoms at follow-up **Time Frame:** 7 days after the maintenance intervention **Description:** Presence of conjunctivitis symptoms after the maintenance intervention **Measure:** Conjunctivitis symptoms at follow-up **Time Frame:** 7 days after the maintenance intervention ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * male or female gender * age between 7 and 11 years Exclusion Criteria: * no exclusion criteria **Maximum Age:** 11 Years **Minimum Age:** 7 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Palermo **Country:** Italy **Facility:** Institute of Translational Pharmacology **Zip:** 90146 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04838379 **Brief Title:** Ultrasound Guided Rectus Sheath Block and Transversus Abdominis Plane Block **Official Title:** Perioperative Analgesic Effect of Preemptive Ultrasound Guided Rectus Sheath Block and Transversus Abdominis Plane Block With Dexmedetomidine vs Dexamethasone for Laparoscopic Surgery in Paediatrics #### Organization Study ID Info **ID:** 01210861577 #### Organization **Class:** OTHER **Full Name:** Assiut University ### Status Module #### Completion Date **Date:** 2023-01-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-04-20 **Type:** ACTUAL **Last Update Submit Date:** 2023-04-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-05-20 **Type:** ACTUAL #### Start Date **Date:** 2021-04-01 **Type:** ACTUAL **Status Verified Date:** 2023-04 #### Study First Post Date **Date:** 2021-04-09 **Type:** ACTUAL **Study First Submit Date:** 2021-03-31 **Study First Submit QC Date:** 2021-04-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assiut University #### Responsible Party **Investigator Affiliation:** Assiut University **Investigator Full Name:** Kirolos Gamal Reda **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The current study aimed to assess the efficacy of Dexmedetomidine (DEX) and Dexamethasone as an adjuvant to ultrasound guided TAP and RS block to prolongation of postoperative analgesia and better pain control in children undergoing laparoscopic surgeries **Detailed Description:** Laparoscopic surgeries are one of the most frequently performed paediatric surgeries . Although minimally invasive, this technique is still associated with a significant amount of pain and anxiety in children . Indeed, children who are highly anxious prior to surgery tend to have more postoperative pain, delayed hospital discharge, and higher incidence of emergence delirium, sleep disturbances, and other mal-adaptive behaviour changes that can last up to a few weeks following surgery . To improve analgesia and decrease postoperative anxiety in children undergoing laparoscopic appendectomies multimodal approach for pain control can be employed. Over the past years, the concept of pain management has extended from simply decreasing pain intensity to optimizing patient's condition. The goal is to decrease pain scores, stress response that should be avoided in patients, particularly cardiac patients, together with a decrease in analgesics-related adverse effects like nausea, vomiting, retention of urine and over sedation. By achieving these goals, we can certainly facilitate patient recovery and minimize the hospital stay. Improved pain control can be achieved by a combination of different types of regional analgesia with systemic analgesics. The main contributor to pain post abdominal operations is the pain from abdominal wall incision . Many procedures were followed to decrease this intense postoperative pain such as, epidural catheter analgesia, transversus abdominis plane (TAP) block, local wound infiltration, Patient-Controlled Analgesia (PCA), peripheral nerve blocks, in addition to systemic administration of Non-Steroidal Anti- Inflammatory Drugs (NSAIDs) or opioids . The transversus abdominis plane (TAP) block is a regional anesthetic technique that provides analgesia to the parietal peritoneum as well as to the skin and muscles of the anterior abdominal wall (9-10). Despite a relatively low risk of complications and a high success rate using modern techniques, TAP block remains overwhelmingly underused. Although the technique is technically straightforward, it has not been adopted in clinical practice . Moreover, The Rectus Sheath Block (RSB) is one of these regional techniques that are suitable for operations with a midline incision or laparoscopic surgery with the main incision at the umbilical port. A previous study showed the analgesic efficacy of ultrasound guided rectus sheath block for laparoscopic appendectomy compared to a control group injected with saline instead of a local anesthetic Generally, in laparoscopic surgeries, the sites of port incision are associated with considerable postoperative discomfort. Thus, we performed TAP and RS block to ameliorate postoperative pain and improve patient outcomes. In addition to the usefulness of traditional local anesthetics to provide analgesia during the course of the postoperative period is restricted by their short duration of action . Dexmedetomidine (DEX) and Dexamethasone has been shown as a valuable additives to local anesthetics in neuraxial blocks and peripheral nerve blocks leading to prolongation of postoperative analgesia and better pain control . Dexmedetomidine (DEX) α-2 adrenergic receptor consists of three α-2 isoreceptors (α-2a, α-2b and α-2c), which regulate the various pharmacodynamic effects of this drug . The α-2a receptor seems to promote sedation and anxiolysis in the locus coeruleus, as well as to generate bradycardia and peripheral vasodilation by stimulation of the cerebral vasomotor center. The α-2b receptor prevents tremor, generates analgesia in the dorsal horns of the spinal cord and determines peripheral vasoconstriction. The α-2c receptor modulates the mental state . Dexamethasone, a high-potency, long-acting glucocorticoid, has been shown to prolong peripheral nerve blockade . Dexamethasone binds to glucocorticoid receptors and inhibits potassium conductance, which decreases nociceptive C-fiber activity . Dexamethasone may also extend the duration of analgesia via local vasoconstrictive and systemic anti-inflammatory effects . Thus, we performed TAP and RS block to ameliorate postoperative pain and improve patient outcomes. . ### Conditions Module **Conditions:** - Cholecystitis - Appendicitis **Keywords:** - us guided rectus sheath block&tap block - laparscopic surgery - regional anesthesia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Age: 8-12years. * Weight: 20-60 kg. * Sex: both males and females. * ASA physical status: I-II. ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 90 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** will include 30 patients: each one will receive 2.5 mg/kg of 0.25% bupivacaine diluted in a 20 mL syringe of normal saline, 10 minutes before skin incision **Intervention Names:** - Drug: Dexmedetomidine **Label:** group Bupivacaine **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** will include 30 patients: each one will receive 2.5mg/kg of 0.25% bupivacaine plus 1 µ/kg of dexmedetomidine diluted in a 20 mL syringe of normal saline, 10 minutes before skin incision **Intervention Names:** - Drug: Dexmedetomidine **Label:** group bupivacaine&dex **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** will include 30 patients: each one will receive 2.5 mg/kg of 0.25% bupivacaine plus dexamethasone (0.3 mg/kg) diluted in a 20 mL syringe of normal saline , 10 minutes before skin incision **Intervention Names:** - Drug: Dexmedetomidine **Label:** Group bupivacaine & dexamethasone **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Group bupivacaine & dexamethasone - group Bupivacaine - group bupivacaine&dex **Description:** Ninety patients were randomized to receive ultrasound-guided RSB\&tap block After the induction of anesthesia and patient stabilization, the abdomen was sterilized and draped. Then, under complete aseptic conditions, ultrasound-guided Bilateral Rectus Sheath Block \& tap block was performed **Name:** Dexmedetomidine **Other Names:** - Dexamethasone - Bupivacaine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** the time of the first call for analgesia is recorded **Measure:** evaluate the first call for rescue analgesia **Time Frame:** 24 hours after recovery from anesthesia ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ● Age: 8-12years. * Weight: 20-60 kg. * Sex: both males and females. * ASA physical status: I-II. Exclusion Criteria: * • Patient's guardian refusal to participate in the study. * Patients having known hypersensitivity to dexametomidine will be excluded. * Patients with cardiovascular, liver or renal disease, unsatisfactory preoperative peripheral arterial oxygen saturation, neurological or psychiatric disease and coagulation disturbances. * Any perioperative cardiovascular or respiratory event occurred or difficulties in pain perception and assessment which make the study intervention clinically unacceptable. * Patients on regular use of analgesic or who received analgesic 24 h before surgery **Maximum Age:** 12 Years **Minimum Age:** 8 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Assiut **Country:** Egypt **Facility:** Assiut university **Zip:** 71511 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000059413 - Term: Intraabdominal Infections - ID: D000007239 - Term: Infections - ID: D000005759 - Term: Gastroenteritis - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000002429 - Term: Cecal Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000005705 - Term: Gallbladder Diseases - ID: D000001660 - Term: Biliary Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M6005 - Name: Cholecystitis - Relevance: HIGH - As Found: Cholecystitis - ID: M25019 - Name: Acalculous Cholecystitis - Relevance: LOW - As Found: Unknown - ID: M4376 - Name: Appendicitis - Relevance: HIGH - As Found: Appendicitis - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M29465 - Name: Intraabdominal Infections - Relevance: LOW - As Found: Unknown - ID: M8875 - Name: Gastroenteritis - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M5679 - Name: Cecal Diseases - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M8823 - Name: Gallbladder Diseases - Relevance: LOW - As Found: Unknown - ID: M4946 - Name: Biliary Tract Diseases - Relevance: LOW - As Found: Unknown - ID: T1150 - Name: Cholecystitis - Relevance: HIGH - As Found: Cholecystitis ### Condition Browse Module - Meshes - ID: D000001064 - Term: Appendicitis - ID: D000002764 - Term: Cholecystitis ### Intervention Browse Module - Ancestors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000000932 - Term: Antiemetics - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000005765 - Term: Gastrointestinal Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000018931 - Term: Antineoplastic Agents, Hormonal - ID: D000000970 - Term: Antineoplastic Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000779 - Term: Anesthetics, Local - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000018689 - Term: Sensory System Agents - ID: D000006993 - Term: Hypnotics and Sedatives - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000058647 - Term: Adrenergic alpha-2 Receptor Agonists - ID: D000000316 - Term: Adrenergic alpha-Agonists - ID: D000000322 - Term: Adrenergic Agonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: AnEm - Name: Antiemetics - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics - Abbrev: CNSDep - Name: Central Nervous System Depressants ### Intervention Browse Module - Browse Leaves - ID: M7102 - Name: Dexamethasone - Relevance: HIGH - As Found: Children - ID: M22662 - Name: Dexmedetomidine - Relevance: HIGH - As Found: Twice daily - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M5315 - Name: Bupivacaine - Relevance: HIGH - As Found: Following - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M235549 - Name: Dexamethasone acetate - Relevance: LOW - As Found: Unknown - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4251 - Name: Antiemetics - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown - ID: M10043 - Name: Hypnotics and Sedatives - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M3668 - Name: Adrenergic alpha-Agonists - Relevance: LOW - As Found: Unknown - ID: M3673 - Name: Adrenergic Agonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003907 - Term: Dexamethasone - ID: D000020927 - Term: Dexmedetomidine - ID: D000002045 - Term: Bupivacaine ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04259879 **Brief Title:** Molecular Pathways Related to Short-term Fasting Response **Official Title:** Evaluation of p21 Induction and Molecular Pathways Related to Short-term Fasting Response #### Organization Study ID Info **ID:** IMD PI0025 #### Organization **Class:** OTHER **Full Name:** IMDEA Food ### Status Module #### Completion Date **Date:** 2016-06-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-02-17 **Type:** ACTUAL **Last Update Submit Date:** 2020-02-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-05-18 **Type:** ACTUAL #### Start Date **Date:** 2016-04-07 **Type:** ACTUAL **Status Verified Date:** 2020-01 #### Study First Post Date **Date:** 2020-02-07 **Type:** ACTUAL **Study First Submit Date:** 2020-02-05 **Study First Submit QC Date:** 2020-02-05 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Centro Nacional de Investigaciones Oncologicas CARLOS III #### Lead Sponsor **Class:** OTHER **Name:** IMDEA Food #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will evaluate the effect of short-term fasting (36 hours) in gene expression in blood cells in healthy volunteers. **Detailed Description:** Fasting is a nutritional intervention consisting on the restriction of nutrient intake during a relatively long period of time. It elicits a profound metabolic reprogramming aimed at shifting nutrient supply from external food intake to internal stored nutrients. Periodic activation of this complex response, termed periodic or intermittent fasting (IF), elicits numerous protective effects against aging, metabolic alterations, neurological disorders and cardiovascular health. Short-term fasting is protective in different stress scenarios, including ischemia reperfusion, bouts of inflammation and chemotherapy-induced toxicity, and improves the anti-tumor efficacy of chemotherapy. Although the basic physiology of fasting is well known, the molecular mechanisms underlying its beneficial effects are not yet completely understood. In mammals, the response to short-term fasting (from 12 to 48 hours) in terms of nutrient mobilization through the bloodstream has been extensively studied. Fasting follows sequential phases, during which nutrients are released from different storing depots. First, glucose is released from glycogen stores in the liver and muscle. Upon depletion of glycogen, two fasting mechanisms are activated: fatty acids are exported from the adipose tissue into the bloodstream in the form of free fatty acids (FFAs), reaching the liver where they are used to produce ketone bodies, a process termed ketogenesis. Also, gluconeogenesis is activated in the liver, generating glucose mainly from glycerol (released during lipolysis) and amino acids, that originate mainly from muscle breakdown. All these physiological responses are tightly regulated by hormonal and molecular mechanisms. At the hormonal level, fasting induces a decrease in blood insulin, leptin and ghrelin, and an increase in glucagon levels, while blood adiponectin remains unchanged. Also, several signal transduction pathways are affected by fasting. PPARalpha, a nuclear receptor of fatty acids, becomes activated by the fasting-mediated increase in blood Free fatty Acids (FFAs) and triggers the expression of many target genes in several tissues, including blood cells. It has been shown that the Cyclin Dependent Kinase (CDK) inhibitor p21 is highly upregulated during short-term fasting in many mouse tissues. Moreover, it is known that p21-null mice are unable to endure normal periods of fasting and that p21 is required for the full activation of PPARa target genes both in vivo and in isolated hepatocytes. In the current study, the investigators wanted to study for the first time molecular mechanisms of fasting that still remained unexplored, specially the expression induction of p21 and PPARalpha signalling pathway. For this, the investigators analyzed blood samples from healthy volunteers subjected to 36 hours of fasting, to explore gene expression in Peripheral Blood Mononuclear Cells (PBMCs). ### Conditions Module **Conditions:** - Fasting **Keywords:** - Short-term Fasting - molecular mechanisms - p21 - Peripheral blood mononuclear cells (PBMCs) - PPARalpha ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** This study was an Interventional study. There were three evaluations: the basal one was an initial evaluation after overnight fasting, the second evaluation 24 hours later (36 hours fasting) and the third one 24 hours post-refeeding. ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The participants will follow a short-term fasting period for 36 hours **Intervention Names:** - Other: Fasting **Label:** Fasting **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Fasting **Description:** Food intake restriction **Name:** Fasting **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Expression analysis of p21, Pyruvate Dehydrogenase Kinase 4 (PDK4), Carnitine palmitoyltransferase 1 (CPT1), Adipophilin (ADFP) and Solute carrier family 25, member 50 (SLC25A50) were performed in a HT-7900 Fast Real time polymerase chain reaction (PCR). Quantifications were made applying the ΔCt method (ΔCt = \[Ct of gene of interest - Ct of housekeeping\]). The housekeeping genes used for input normalization were β-actin (ACTB) and ribosomal protein lateral stalk subunit P0 (RPLP0). **Measure:** Changes in gene expression in PBMCs after fasting **Time Frame:** Baseline, 24 hours and 48 hours later #### Secondary Outcomes **Description:** Insulin levels (International Units per milliliter) were measured with a kit from Abbott Laboratories, by luminescent immunoassay using the Architect instrument from Abbott Laboratories. **Measure:** Changes in Insulin levels in response to fasting **Time Frame:** Baseline, 24 hours and 48 hours later **Description:** Free fatty acids levels (moles per milliliter) were evaluated with a kit from Abbott Laboratories, by enzymatic spectrophotometric assays using an Architect instrument from Abbott Laboratories. **Measure:** Changes in Free Fatty Acids levels in response to fasting **Time Frame:** Baseline, 24 hours and 48 hours later **Description:** Ketone bodies concentration (moles per milliliter) will be measured with a kit from Sigma-Aldrich, by an enzymatic spectrophotometric assay using an microplate reader from Thermo Fisher. **Measure:** Changes ketone bodies in response to fasting **Time Frame:** Baseline, 24 hours and 48 hours later **Description:** Leptin levels (nanograms per milliliter) were measured with a kit from Mercodia by a non-competitive automatic ELISA immunoanalysis **Measure:** Changes in leptin levels in response to fasting **Time Frame:** Baseline, 24 hours and 48 hours later **Description:** To evaluate lipid improvements the following measurements were considered: Triacylglycerol, Total Cholesterol, low Density Lipoprotein and High-Density Lipoprotein measured by routine laboratory (CQS, Madrid, Spain) methods. **Measure:** Changes in lipid profile in response to fasting **Time Frame:** Baseline, 24 hours and 48 hours later **Description:** To evaluate the tolerance to fasting, participants will fill in a fasting tolerance test based on the symptoms they feel, this will result in a final score of tolerance to fasting. **Measure:** Subjective evaluation of tolerance to fasting **Time Frame:** 36 hours of fasting ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Men and women between 18 - 50 years old. * BMI \>20\<30 * Adequate education level and comprehension of the clinical study * Willingness to participate in the study as a volunteer and to provide written consent Exclusion Criteria: * BMI \<20 (thinness) * BMI \>30 (obesity) * Abnormal low glucose levels after fasting * Having donated blood less than 8 weeks before starting the study * Subjects who report special discomfort after previous periods of short fasting * Diagnosis of type 2 Diabetes mellitus (insulin-dependent) * Dyslipidemia under pharmacological treatment * High blood pressure under pharmacological treatment * Dementia, neurological disease or reduction of cognitive function * Severe illness (hepatic disease, renal disease, etc * Taking medications that could affect the lipid and glycemic profiles (statins, fibrate, diuretics, corticoids, anti-inflammatory, hypoglycemic or insulin) 30 days before the beginning of the study. * Taking medications or substances for weight loss management (15 days before the beginning of the study) * Pregnancy or lactation **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Madrid **Country:** Spain **Facility:** IMDEA Food **Zip:** 28049 #### Overall Officials **Official 1:** **Affiliation:** IMDEA Food **Name:** Pablo J Fernandez-Marcos, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Spanish National Cancer Research Center **Name:** Manuel Serrano Marugán, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Antoni R, Johnston KL, Collins AL, Robertson MD. Effects of intermittent fasting on glucose and lipid metabolism. Proc Nutr Soc. 2017 Aug;76(3):361-368. doi: 10.1017/S0029665116002986. Epub 2017 Jan 16. **PMID:** 28091348 **Citation:** Arnason TG, Bowen MW, Mansell KD. Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. World J Diabetes. 2017 Apr 15;8(4):154-164. doi: 10.4239/wjd.v8.i4.154. **PMID:** 28465792 **Citation:** Gotthardt JD, Verpeut JL, Yeomans BL, Yang JA, Yasrebi A, Roepke TA, Bello NT. Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice. Endocrinology. 2016 Feb;157(2):679-91. doi: 10.1210/en.2015-1622. Epub 2015 Dec 14. **PMID:** 26653760 **Citation:** Halberg N, Henriksen M, Soderhamn N, Stallknecht B, Ploug T, Schjerling P, Dela F. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985). 2005 Dec;99(6):2128-36. doi: 10.1152/japplphysiol.00683.2005. Epub 2005 Jul 28. **PMID:** 16051710 **Citation:** Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017 Oct;39:46-58. doi: 10.1016/j.arr.2016.10.005. Epub 2016 Oct 31. **PMID:** 27810402 **Citation:** Varady KA, Bhutani S, Church EC, Klempel MC. Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr. 2009 Nov;90(5):1138-43. doi: 10.3945/ajcn.2009.28380. Epub 2009 Sep 30. **PMID:** 19793855 **Citation:** Vasconcelos AR, Yshii LM, Viel TA, Buck HS, Mattson MP, Scavone C, Kawamoto EM. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment. J Neuroinflammation. 2014 May 6;11:85. doi: 10.1186/1742-2094-11-85. **PMID:** 24886300 **Citation:** Tinkum KL, Stemler KM, White LS, Loza AJ, Jeter-Jones S, Michalski BM, Kuzmicki C, Pless R, Stappenbeck TS, Piwnica-Worms D, Piwnica-Worms H. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival. Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):E7148-54. doi: 10.1073/pnas.1509249112. Epub 2015 Dec 7. **PMID:** 26644583 **Citation:** Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, Cohen P, Longo VD. Fasting and cancer treatment in humans: A case series report. Aging (Albany NY). 2009 Dec 31;1(12):988-1007. doi: 10.18632/aging.100114. **PMID:** 20157582 **Citation:** Raffaghello L, Safdie F, Bianchi G, Dorff T, Fontana L, Longo VD. Fasting and differential chemotherapy protection in patients. Cell Cycle. 2010 Nov 15;9(22):4474-6. doi: 10.4161/cc.9.22.13954. Epub 2010 Nov 15. **PMID:** 21088487 **Citation:** Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, Pistoia V, Wei M, Hwang S, Merlino A, Emionite L, de Cabo R, Longo VD. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012 Mar 7;4(124):124ra27. doi: 10.1126/scitranslmed.3003293. Epub 2012 Feb 8. **PMID:** 22323820 **Citation:** Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, Cacciottolo M, Martin-Montalvo A, de Cabo R, Wei M, Morgan TE, Longo VD. Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. Cancer Cell. 2016 Jul 11;30(1):136-146. doi: 10.1016/j.ccell.2016.06.005. **PMID:** 27411588 **Citation:** Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, Levesque S, Castoldi F, Jacquelot N, Yamazaki T, Senovilla L, Marino G, Aranda F, Durand S, Sica V, Chery A, Lachkar S, Sigl V, Bloy N, Buque A, Falzoni S, Ryffel B, Apetoh L, Di Virgilio F, Madeo F, Maiuri MC, Zitvogel L, Levine B, Penninger JM, Kroemer G. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell. 2016 Jul 11;30(1):147-160. doi: 10.1016/j.ccell.2016.05.016. **PMID:** 27411589 **Citation:** Ruderman NB. Muscle amino acid metabolism and gluconeogenesis. Annu Rev Med. 1975;26:245-58. doi: 10.1146/annurev.me.26.020175.001333. No abstract available. **PMID:** 1096762 **Citation:** Cahill GJ Jr, Owen OE, Morgan AP. The consumption of fuels during prolonged starvation. Adv Enzyme Regul. 1968;6:143-50. doi: 10.1016/0065-2571(68)90011-3. No abstract available. **PMID:** 5720334 **Citation:** Nuttall FQ, Almokayyad RM, Gannon MC. Comparison of a carbohydrate-free diet vs. fasting on plasma glucose, insulin and glucagon in type 2 diabetes. Metabolism. 2015 Feb;64(2):253-62. doi: 10.1016/j.metabol.2014.10.004. Epub 2014 Oct 8. **PMID:** 25458830 **Citation:** Nuttall FQ, Almokayyad RM, Gannon MC. The ghrelin and leptin responses to short-term starvation vs a carbohydrate-free diet in men with type 2 diabetes; a controlled, cross-over design study. Nutr Metab (Lond). 2016 Jul 22;13:47. doi: 10.1186/s12986-016-0106-x. eCollection 2016. **PMID:** 27453716 **Citation:** Merl V, Peters A, Oltmanns KM, Kern W, Born J, Fehm HL, Schultes B. Serum adiponectin concentrations during a 72-hour fast in over- and normal-weight humans. Int J Obes (Lond). 2005 Aug;29(8):998-1001. doi: 10.1038/sj.ijo.0802971. **PMID:** 15917861 **Citation:** Bouwens M, Afman LA, Muller M. Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid beta-oxidation: functional role of peroxisome proliferator activated receptor alpha in human peripheral blood mononuclear cells. Am J Clin Nutr. 2007 Nov;86(5):1515-23. doi: 10.1093/ajcn/86.5.1515. **PMID:** 17991667 **Citation:** Lopez-Guadamillas E, Fernandez-Marcos PJ, Pantoja C, Munoz-Martin M, Martinez D, Gomez-Lopez G, Campos-Olivas R, Valverde AM, Serrano M. p21Cip1 plays a critical role in the physiological adaptation to fasting through activation of PPARalpha. Sci Rep. 2016 Oct 10;6:34542. doi: 10.1038/srep34542. **PMID:** 27721423 **Citation:** Prokesch A, Graef FA, Madl T, Kahlhofer J, Heidenreich S, Schumann A, Moyschewitz E, Pristoynik P, Blaschitz A, Knauer M, Muenzner M, Bogner-Strauss JG, Dohr G, Schulz TJ, Schupp M. Liver p53 is stabilized upon starvation and required for amino acid catabolism and gluconeogenesis. FASEB J. 2017 Feb;31(2):732-742. doi: 10.1096/fj.201600845R. Epub 2016 Nov 3. **PMID:** 27811061 **Citation:** Tinkum KL, White LS, Marpegan L, Herzog E, Piwnica-Worms D, Piwnica-Worms H. Forkhead box O1 (FOXO1) protein, but not p53, contributes to robust induction of p21 expression in fasted mice. J Biol Chem. 2013 Sep 27;288(39):27999-8008. doi: 10.1074/jbc.M113.494328. Epub 2013 Aug 5. **PMID:** 23918930 ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03641079 **Brief Title:** Identification of Compound From Brinjal Peel Extract in the Treatment of Palmar Arsenical Keratosis and Bowen's Disease **Official Title:** Identification of Compound From Brinjal Peel Extract That is Effective in the Treatment of Severe Palmar Arsenical Keratosis and Bowen's Disease #### Organization Study ID Info **ID:** No.BSMMU/2018/2961 #### Organization **Class:** OTHER **Full Name:** Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh ### Status Module #### Completion Date **Date:** 2019-02 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2018-08-21 **Type:** ACTUAL **Last Update Submit Date:** 2018-08-18 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-12 **Type:** ESTIMATED #### Start Date **Date:** 2017-09-16 **Type:** ACTUAL **Status Verified Date:** 2018-04 #### Study First Post Date **Date:** 2018-08-21 **Type:** ACTUAL **Study First Submit Date:** 2018-08-18 **Study First Submit QC Date:** 2018-08-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh #### Responsible Party **Investigator Affiliation:** Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh **Investigator Full Name:** Dr. Razia Sultana **Investigator Title:** Resident **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Arsenicosis is a major health problem in Bangladesh. Long term exposure of arsenic causes keratosis of palm which reduce working capacity of patient. It also causes invasive skin lesions like Bowen's disease which has a risk to develop squamous cell carcinoma. Brinjal peel is well known for its antioxidant and anticancer properties. So this study will be conducted to identify the compound from brinjal peel extract and to see its outcome on keratosis and Bowen's disease. **Detailed Description:** Arsenicosis is a major health problem in Bangladesh. About half of the population are chronically exposed to high concentration of arsenic through contaminated drinking water. In arsenicosis, keratosis of palm and sole occur which reduce the working capacity of the patient and affect the socioeconomic condition. It also causes invasive skin lesions like Bowen's disease, squamous cell carcinoma, and basal cell carcinoma. Bowen's disease usually appears as a persistent reddened scaly patch on the skin and has a risk (3-5%) to develop squamous cell carcinoma. Keratosis can be treated by different topical preparations like salicylic acid, propylene glycol and oral antioxidant, zinc and folic acid, but treatment by these medicines require a longer time to relieve and thus reduce patient's compliance. On the other hand, treatment options available for Bowen's disease are expensive. Brinjal is a common vegetable which contains steroidal alkaloids, steroidal glycosides, delphinidine, nasunin and other biologically active compounds. These biologically active compounds are effective against human cancer cells by various mechanisms. One study shows that a topical cream prepared from brinjal peel extract is effective in keratosis and skin carcinoma. So, this study will be conducted to see the outcome of brinjal peel extract in severe palmar arsenical keratosis and Bowen's disease and to identify the compound that is responsible for the effect. The study will be an Open Phase- II Clinical Trial. It will be conducted in Bangabandhu Sheikh Mujib Medical University and Bhanga Upazilla of Faridpur District. Extracts from brinjal peel will be collected by using a mixture of ethanol, chloroform and acetic acid as a solvent in Soxhlet extractor and rotary evaporator. Thin Layer Chromatography (TLC), Nuclear Magnetic Resonance (NMR) and Infrared (IR) of extract will be done to identify compound. Cytotoxicity assay will be done by using brine shrimp bioassay. Then a topical cream will be prepared from the extract and supplied at the field level through a temporary arsenic clinic at an interval of two weeks. Instruction will be given to the patients about applying the cream. Adherence and adverse effects of the cream will be monitored regularly through phone calls and during each visit. Photograph will be taken and size of the keratotic nodules as well as, lesions of Bowen's disease will be measured before the start and after completion of treatment. Clinical improvement will be assessed by the mean scoring of nodules and lesions and perception of patients about their improvement by using Likert Scale. Statistical analysis and results will be presented in tabulated forms and in different diagrams. ### Conditions Module **Conditions:** - Keratotic Nodular Size ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 36 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** intervention-brinjal peel extract containing cream, dose-twice daily for 12 weeks **Intervention Names:** - Drug: Brinjal peel extract containing cream **Label:** brinjal peel extract containing cream **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - brinjal peel extract containing cream **Description:** Brinjal peel extract, white wax, white petrolatum, stearyl alcohol **Name:** Brinjal peel extract containing cream **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Nodular size and lesion size will be measured by slide calipers **Measure:** Keratotic nodular size and lesion size of Bowen's disease **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Presence of severe keratosis and/or Bowen's disease * Drinking arsenic contaminated water for at least six months * Patient voluntarily agreed to participate Exclusion Criteria: * Age less than 18 years or more than 60 years * Pregnant and nursing mother * Skin diseases like atopic dermatitis, eczema and psoriasis **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Razia Sultana, MBBS **Phone:** 01715995605 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Ashraful Islam, MBBS **Phone:** 01715995605 **Role:** CONTACT #### Locations **Location 1:** **City:** Bhanga **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Razia Sultana, MBBS - **Phone:** 01715995605 - **Role:** CONTACT ***Contact 2:*** - **Name:** Shafiq Rahman - **Phone:** 01762262836 - **Role:** CONTACT **Country:** Bangladesh **Facility:** Faridpur **State:** Hamirdi Community Clinic **Status:** RECRUITING **Zip:** 7830 #### Overall Officials **Official 1:** **Affiliation:** Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh **Name:** Razia Sultana, MBBS **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012871 - Term: Skin Diseases - ID: D000009369 - Term: Neoplasms - ID: D000002294 - Term: Carcinoma, Squamous Cell - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000018307 - Term: Neoplasms, Squamous Cell ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M28268 - Name: Keratosis, Actinic - Relevance: LOW - As Found: Unknown - ID: M10668 - Name: Keratosis - Relevance: HIGH - As Found: Keratosis - ID: M5190 - Name: Bowen's Disease - Relevance: HIGH - As Found: Bowen's Disease - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M20451 - Name: Neoplasms, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: T810 - Name: Bowen's Disease - Relevance: HIGH - As Found: Bowen's Disease ### Condition Browse Module - Meshes - ID: D000001913 - Term: Bowen's Disease - ID: D000007642 - Term: Keratosis ### Intervention Browse Module - Browse Branches - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: CNSDep - Name: Central Nervous System Depressants ### Intervention Browse Module - Browse Leaves - ID: M13485 - Name: Petrolatum - Relevance: LOW - As Found: Unknown - ID: M3777 - Name: Ethanol - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04398979 **Brief Title:** Surgical Ablation for Atrial Fibrillation **Official Title:** Minimally Invasive Surgical Ablation for Standalone Atrial Fibrillation #### Organization Study ID Info **ID:** JPSH-AF2012 #### Organization **Class:** OTHER **Full Name:** Nanjing Medical University ### Status Module #### Completion Date **Date:** 2020-02-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-05-22 **Type:** ACTUAL **Last Update Submit Date:** 2020-05-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-12-31 **Type:** ACTUAL #### Start Date **Date:** 2012-01-01 **Type:** ACTUAL **Status Verified Date:** 2020-05 #### Study First Post Date **Date:** 2020-05-22 **Type:** ACTUAL **Study First Submit Date:** 2020-05-19 **Study First Submit QC Date:** 2020-05-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nanjing Medical University #### Responsible Party **Investigator Affiliation:** Nanjing Medical University **Investigator Full Name:** Hong Liu **Investigator Title:** Investigator of the First Hospital of Nanjing Medical University **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Minimally invasive approaches for surgical treatment have been advocated as a treatment option for stand-alone atrial fibrillation (AF). This study will investigate the clinical outcomes after minimally invasive surgical ablation of both paroxysmal and persistent/longstanding persistent AF. **Detailed Description:** Atrial fibrillation (AF) patients with a previous stroke are often at a high risk of recurrent stroke and bleeding. Minimally invasive approaches for surgical treatment have been advocated as a treatment option for stand-alone AF. This study will investigate the clinical outcomes after minimally invasive surgical ablation of both paroxysmal and persistent/longstanding persistent AF. Neurological safety will be assessed by cerebral magnetic resonance, neuropsychological examination and periprocedural transcranial Doppler measurement. ### Conditions Module **Conditions:** - Atrial Fibrillation ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 300 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** After blunt dissection of the oblique and transverse sinus, an AtriCure Lumitip Dissector was introduced around the pulmonary veins. Pulmonary vein isolation was achieved with an AtriCure Isolator Synergy ablation clamp around the pulmonary vein antrum at least six times for each side. Ganglionated plexus identification and ablation were performed using an AtriCure Synergy ablation pen. The additional superior and inferior ablation lines connecting the bilateral pulmonary vein isolations were created by applying the AtriCure Synergy ablation pen. Following completion of the ablation on the right side, ablation on the left side was accomplished in a similar manner. The ligament of Marshall was dissected by electrical cautery. Conduction block was confirmed upon completion of the ablation procedure on the left side. **Name:** Thoracoscopic Atrial fibrillation Ablation **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Number of patients with sinus rhythm, without detections of atrial arrhythmias (episodes longer than 30 seconds) **Measure:** efficacy - sinus rhythm **Time Frame:** 1 year #### Secondary Outcomes **Description:** conversion to sternotomy, bleeding, thromboembolic events, tamponade, haemothorax, pneumothorax, pleural effusion, pneumonia **Measure:** periprocedural complications - surgery **Time Frame:** 30 days after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients age \> 18 years * Patients with paroxysmal, or persistent/long-standing persistent AF according to the standard EHRA definition. * Patients with symptomatic AF that is refractory to at least one antiarrhythmic medication. * Absence of significant structural heart disease (dilated cardiomyopathy, hypertrophic cardiomyopathy, valvular heart disease, untreated coronary artery disease) Exclusion Criteria: * AF secondary to a reversible cause (i.e., thyreopathy, etc.) Indication for open-heart surgery (coronary artery bypass grafting, valve surgery, etc.) * Severe left ventricle dysfunction that is clearly caused by some other cardiac disease (dilated cardiomyopathy, ischaemic heart disease, etc.) where the AF is clearly of secondary etiology * Known severe pericardial and pleural adhesions (e.g., history of cardiac surgery) **Maximum Age:** 85 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** patients with symptomatic, drug-resistant, stand-alone, paroxysmal, persistent or long-standing persistent atrial fibrillation ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Tanaka K, Koga M, Lee KJ, Kim BJ, Park EL, Lee J, Mizoguchi T, Yoshimura S, Cha JK, Lee BC, Nakahara J, Suzuki N, Bae HJ, Toyoda K; CRCS-K Investigators and the SAMURAI Study Investigators. Atrial Fibrillation-Associated Ischemic Stroke Patients With Prior Anticoagulation Have Higher Risk for Recurrent Stroke. Stroke. 2020 Apr;51(4):1150-1157. doi: 10.1161/STROKEAHA.119.027275. Epub 2020 Feb 26. Erratum In: Stroke. 2020 May;51(5):e99. **PMID:** 32098607 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4586 - Name: Atrial Fibrillation - Relevance: HIGH - As Found: Atrial Fibrillation - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001281 - Term: Atrial Fibrillation ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04882579 **Brief Title:** Point-of-care Ultrasound in Suspected Pulmonary Embolism **Official Title:** Point-of-care Ultrasound in the Diagnostic Work-up of Suspected Pulmonary Embolism - a Multicenter Randomized Controlled Trial #### Organization Study ID Info **ID:** PulmonaryEmbolismPoCUSOdense #### Organization **Class:** OTHER **Full Name:** Odense University Hospital ### Status Module #### Completion Date **Date:** 2023-07-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-03 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-02-01 **Type:** ACTUAL #### Start Date **Date:** 2021-06-15 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2021-05-12 **Type:** ACTUAL **Study First Submit Date:** 2021-04-12 **Study First Submit QC Date:** 2021-05-08 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Southern Denmark **Class:** OTHER **Name:** Snedkermester Sophus Jacobsen and hustru Astrid Jacobsens Foundation **Class:** OTHER **Name:** Odense Patient Data Explorative Network #### Lead Sponsor **Class:** OTHER **Name:** Odense University Hospital #### Responsible Party **Investigator Affiliation:** Odense University Hospital **Investigator Full Name:** Casper Falster **Investigator Title:** Principal investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Pulmonary embolism (PE) is a common cardiovascular condition with an estimated incidence of 0.60 to 1.12 per 1000 inhabitants in the United States of America, and the diagnosis is challenging as patients with PE present with a wide array of symptoms. Computed tomography pulmonary angriography (CTPA) and lung ventilation-perfusion scintigraphy (VQ) are considered the gold-standards in PE-diagnostics but may not always be feasible. CTPA is contraindicated by contrast allergy or renal failure and both modalities require involvement of multiple staff-members and transport of the patient. Lung scintigraphy cannot be performed in an emergency situation, with unstable patients and patients unable to comply to the examination. Ultrasound represent a possible tool in confirming or dismissing clinical PE suspicion. Ultrasound is non-invasive and can be performed bedside by the clinician, an approach known as point-of-care ultrasound (PoCUS), reducing both time, radiation-exposure and costs. The aim of this study is to investigate whether integrating cardiac, lung and deep venous ultrasound in the clinical evaluation of suspected PE reduces the need for referral to CTPA or lung scintigraphy, during emergency department work up, while maintaining safety standards. **Detailed Description:** All ultrasound examinations will be performed by a physician certified in ultrasound by the Danish Society for Emergency Physicians in accordance with the Danish Health Agency. Based on ultrasonographic findings, PE suspicion is allocated to one of three categories: 1. Clinical suspicion of PE confirmed if ≥1 of the following ultrasound findings: 1. Visible proximal deep venous thrombus 2. ≥2 hypoechoic subpleural lung consolidations with a diameter of ≥0,5cm 3. Visible right ventricular thrombus 4. McConnell's sign if no known pulmonary hypertension, interstitial lung disease, COPD or pulmonary valve disease 5. D-sign present in both systole and diastole if no known pulmonary hypertension, interstitial lung disease, COPD or pulmonary valve disease If PE is confirmed by ultrasound, the physician will apply the simplified pulmonary embolism severity index score (sPESI) and estimate risk of mortality within 30 days based on clinical signs and symptoms, cardiac troponin level and RV dysfunction. Patients with intermediate-high or high risk, requiring admission to a cardiology department will be referred for CTPA. Patients with low or intermediate-low risk, not requiring admission, will be discharged with anticoagulative treatment. A thorough presentation of the sPESI-score and early mortality risk assessment is available in the 2019 collaborative guidelines by the ERS and ESC on the diagnosis and management of PE. 2. Further diagnostic imaging (CTPA or V/Q) required if ≥1 of the following ultrasound findings: 1. 1 hypoechoic subpleural lung consolidation with a diameter of ≥0,5cm 2. Pleural effusion not explained by other cause 3. Basal RVEDD/LVEDD \>1.0 or an RV visibly larger than the LV 4. TAPSE \<17 mm 5. No deep venous thrombus, no lung consolidation or effusion, no signs of RV strain or thrombus but strong clinical suspicion. 6. McConnell's or D-sign in the presence of known pulmonary hypertension, interstitial lung disease, COPD or pulmonary valve disease If PE suspicion can be neither dismissed nor confirmed after ultrasound investigation, the patient will be referred to further investigation as usual with CTPA or lung scintigraphy. Subsequent plan will be in accordance with department guidelines. 3. Clinical suspicion of PE dismissed if ≥1 of the following ultrasound findings: 1. No deep venous thrombus, no lung consolidation or effusion, no signs of RV strain or thrombus and a plausible differential diagnosis or low clinical suspicion 2. Obvious differential diagnosis demonstrated on ultrasound (i.e., pneumonia, pneumothorax, interstitial syndrome, left sided heart failure) If PE suspicion is dismissed by ultrasound investigation, the patient will be either discharged or subject to further investigations in accordance with department guidelines if indicated. ### Conditions Module **Conditions:** - Pulmonary Embolism - Pulmonary Embolus/Emboli **Keywords:** - Ultrasound - Diagnosis - Ultrasonography - Echocardiography ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** 150 patients with suspected pulmonary embolism, requiring CTPA or VQ to finally confirm or dismiss the diagnosis will be enrolled and randomized 1:1 to receive a multiorgan ultrasound investigation or continue to CTPA or VQ as planned. ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 150 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients allocated to the PoCUS investigation arm will receive an ultrasound investigation resulting in either confirmation or dismissal of pulmonary embolism suspicion or requiring CTPA or VQ **Intervention Names:** - Diagnostic Test: Point-of-care-ultrasound examination **Label:** PoCUS group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients allocated to the control group will continue with CTPA or VQ without PoCUS investigation **Label:** Control group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - PoCUS group **Description:** The intervention consists of three ultrasound modalities: 1. Cardiac ultrasound assessing signs of right ventricular strain or other obvious pathology. 2. Deep venous ultrasound assessing presence of a deep venous thrombus 3. Lung ultrasound assessing presence of pulmonary infarctions, pleural effusion, pneumothorax or interstitial syndrome. **Name:** Point-of-care-ultrasound examination **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Measure:** Proportion of patients referred to CTPA or VQ after multiorgan PoCUS **Time Frame:** Up to 24 hours #### Secondary Outcomes **Measure:** Number of adverse events in the intervention and control group after inclusion, including readmission, serious bleeding or death **Time Frame:** 3 months **Measure:** Number of hours until initiation of relevant treatment after clinical evaluation in the control and intervention group. **Time Frame:** Up to 24 hours **Measure:** Proportion of included patients diagnosed with PE in the control and intervention group **Time Frame:** Up to 24 hours **Measure:** Proportion of patients diagnosed with alternative diagnosis following clinical evaluation in the intervention and control group **Time Frame:** Up to 24 hours **Measure:** Proportion of patients in the intervention and control group discharged to their own home following clinical evaluation **Time Frame:** Up to 24 hours **Measure:** Proportion of patients in the reference and control group admitted to a cardiology department for telemetry monitoring (i.e. high risk PE) following clinical evaluation. **Time Frame:** Up to 24 hours **Measure:** Proportion of patients in the reference and control group admitted to an intensive care unit following clinical evaluation **Time Frame:** Up to 24 hours **Measure:** Proportion of patients in the reference and control group referred to supplementary CTPA or lung scintigraphy within 30 days after inclusion **Time Frame:** 30 days **Measure:** Total costs related to diagnostic work up and hospital stay as assessed by HEAT 4.2 **Time Frame:** Up to 1 year **Measure:** Number of subsequent cancer diagnosis in the intervention and control group within 3 months of inclusion **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Referred or Admitted to an emergency department * Clinical suspicion of PE raised by physician requiring further diagnostic imaging (Well's score 0-6 with elevated age-adjusted D-dimer or Wells score \>6 regardless of D-dimer) Exclusion Criteria: * Refusal of informed consent * Pregnancy * Permanent mental disability * Age \<18 years * Diagnosis of PE within the last 6 months * Hemodynamic instability (systolic blood pressure \<90 mmHg for at least two consecutive measurements) * Ultrasound of heart, lungs or deep veins performed prior to enrollment **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Esbjerg **Country:** Denmark **Facility:** Esbjerg Hospital **Zip:** 6700 **Location 2:** **City:** Kolding **Country:** Denmark **Facility:** Kolding Hospital **Zip:** 6000 **Location 3:** **City:** Odense **Country:** Denmark **Facility:** Odense University Hospital **Zip:** 5000 **Location 4:** **City:** Slagelse **Country:** Denmark **Facility:** Slagelse hospital **Zip:** 4200 **Location 5:** **City:** Svendborg **Country:** Denmark **Facility:** Svendborg Hospital **Zip:** 5700 #### Overall Officials **Official 1:** **Affiliation:** Odense University Hospital **Name:** Casper Falster, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Odense University Hospital **Name:** Christian B Laursen, Prof. MD **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000016769 - Term: Embolism and Thrombosis - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14509 - Name: Pulmonary Embolism - Relevance: HIGH - As Found: Pulmonary Embolism - ID: M7784 - Name: Embolism - Relevance: HIGH - As Found: Embolism - ID: M16686 - Name: Thrombosis - Relevance: LOW - As Found: Unknown - ID: M19128 - Name: Embolism and Thrombosis - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011655 - Term: Pulmonary Embolism - ID: D000004617 - Term: Embolism ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT00002279 **Brief Title:** A Study of ddC in Patients With AIDS or Advanced AIDS-Related Complex (ARC) Who Have Not Had Success With Zidovudine (AZT) **Official Title:** Dideoxycytidine (Ro 24-2027). An Open-Label, Safety Study of Dideoxycytidine (ddC) in Patients With AIDS or Advanced ARC Who Cannot Be Maintained on Zidovudine (AZT) Therapy #### Organization Study ID Info **ID:** 031B #### Organization **Class:** INDUSTRY **Full Name:** NIH AIDS Clinical Trials Information Service #### Secondary ID Infos **ID:** N3544C ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2005-06-24 **Type:** ESTIMATED **Last Update Submit Date:** 2005-06-23 **Overall Status:** COMPLETED **Status Verified Date:** 1991-10 #### Study First Post Date **Date:** 2001-08-31 **Type:** ESTIMATED **Study First Submit Date:** 1999-11-02 **Study First Submit QC Date:** 2001-08-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hoffmann-La Roche ### Description Module **Brief Summary:** AMENDED: To provide ddC for patients with AIDS or advanced ARC who have failed treatment with, are intolerant to or are ineligible to receive zidovudine (AZT) and to demonstrate that ddC monotherapy is safe, and tolerable in this patient population. Original design: To provide zalcitabine (dideoxycytidine; ddC) for patients with AIDS or advanced AIDS-related complex (ARC) who have failed treatment with or are intolerant to zidovudine (AZT) and who are also intolerant to dideoxyinosine (ddI); to demonstrate that ddC monotherapy is safe and tolerable in the treatment of patients who previously experienced either treatment failure, hematologic intolerance or myositis with AZT treatment and pancreatitis or other toxicities (except peripheral neuropathy with ddI). **Detailed Description:** The first 50 patients enrolled into the study will be with investigators having prior ddC experience, specifically AIDS Clinical Trials Group (ACTG), or non-ACTG investigators who are listed in ddC protocols NIAID ACTG 012, 112, 047, 050, 106 (N3447), 114 (N3300), 119 (N3492), N3226, or investigators at any ACTG center or ACTG satellite centers with knowledge of ddC therapy. Once all 50 patients have been entered and 25 have completed four weeks of treatment the study will be dependent upon receipt of completed case forms up to week #4 of treatment for the 25 patients who have been reviewed and evaluated for safety. Patients 51-200 may then be entered by any physician licensed in his or her state who has experience with AIDS patients and agrees to follow the patients as specified in the protocol. After all 200 have been entered and week #16 case report forms are returned to the ddC Coordinating Center and reviewed for safety for 100 of the 200 patients, the protocol would be open without limit on numbers of patients. ### Conditions Module **Conditions:** - HIV Infections **Keywords:** - Zalcitabine - Didanosine - Drugs, Investigational - Acquired Immunodeficiency Syndrome - AIDS-Related Complex - Zidovudine ### Design Module #### Design Info ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Zalcitabine **Type:** DRUG ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria Concurrent Medication: Recommended: * Aerosolized Pentamidine or other prophylaxis against Pneumocystis carinii pneumonia (PCP). * Allowed: * Drugs or treatments that could cause other serious additive toxicity when coadministered with study medication will be allowed for treatment of an acute intercurrent illness or opportunistic infection at the discretion of the investigator. * Isoniazid, if there is no evidence of peripheral neuropathy at entry and the patient is taking pyridoxine = or \> 50 mg/day. * Metronidazole, only with a study drug interruption; neurological exam should be performed before and after treatment with metronidazole and ddC restarted only if there are no signs, symptoms or neurological findings suggestive of peripheral neuropathy. * It is recommended that patients requiring amphotericin, pyrimethamine, sulfadiazine, intravenous trimethoprim / sulfamethoxazole, ganciclovir, intravenous pentamidine, intravenous acyclovir or acyclovir = or \> 1000 mg/day orally or other bone marrow or renal toxic drugs have an interruption of ddC until they are stable for two weeks on a maintenance dose of the above medications and only then can ddC be restarted. * Patients on amphotericin, pyrimethamine, sulfadiazine, trimethoprim / sulfamethoxazole, ganciclovir, intravenous acyclovir or acyclovir = or \> 1000 mg/day orally or other bone marrow or renal toxic drugs may not tolerate concomitant ddC. * If these drugs are given concomitantly with ddC, patients should have frequent (weekly) laboratory assessments, as appropriate. * Drugs that are nephrotoxic or have the potential to cause peripheral neuropathy might be expected to cause increased toxicity when co-administered with ddC. Concurrent Treatment: Allowed: * Radiation therapy with dideoxycytidine (ddC) interruption until stable for 2 weeks on treatment. AMENDED: * Treatment categories are now: * AZT treatment failure. AZT intolerance. AZT ineligibility Original design: * Patients must have a diagnosis of AIDS or AIDS-related complex (ARC) and fall into one of the following 2 categories: * Zidovudine (AZT) treatment failure and dideoxyinosine (ddI) intolerance or AZT intolerance and ddI intolerance. Under 18 years of age must have the consent of a parent or guardian. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: * Any history of peripheral neuropathy due to any cause, even if peripheral neuropathy was not the reason for discontinuation of other anti-HIV therapy. * Any finding suggestive of peripheral neuropathy found at neurological exam. If patient has an isolated finding of an absent achilles reflex he may be entered if no signs or symptoms and no other findings are suggestive of peripheral neuropathy. * Neoplasms other than Kaposi's sarcoma or basal cell carcinoma. Concurrent Medication: Excluded: * Other experimental drugs. * Other retroviral nucleoside analogs. * Immunomodulators Systemic corticosteroids. * Drugs with known nephrotoxic or hepatotoxic potential. * Drugs likely to cause peripheral neuropathy. * Avoid due to potential to cause peripheral neuropathy: * Chloramphenicol. * Iodoquinol. * Phenytoin. * Ethionamide. * Gold. * Ribavirin. * Vincristine. * Cisplatin. * Dapsone. * Disulfiram. * Glutethimide. * Hydralazine. * Nitrofurantoin. Patients with the following are excluded: * Any history of peripheral neuropathy due to any cause. * Any finding suggestive of peripheral neuropathy found at baseline neurological exam. * Neoplasms other than Kaposi's sarcoma or basal cell carcinoma. * Unwillingness or deemed unable to sign informed consent. **Minimum Age:** 12 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Nutley **Country:** United States **Facility:** Hoffmann - La Roche Inc **State:** New Jersey **Zip:** 071101199 ### References Module #### References **Citation:** Abrams D, Goldman A, Launer C, Korvick J, Crane L, Deyton L. Results of a randomized open-label comparison trial of ddI and ddC in HIV infected patients who are intolerant of or have failed ZDV therapy; CPCRA 002. The Terry Beirn Community Programs for Clinical Research on AIDS. Int Conf AIDS. 1993 Jun 6-11;9(1):67 (abstract no WS-B24-4) ## Derived Section ### Condition Browse Module - Ancestors - ID: D000015658 - Term: HIV Infections - ID: D000086982 - Term: Blood-Borne Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections - ID: D000015229 - Term: Sexually Transmitted Diseases, Viral - ID: D000012749 - Term: Sexually Transmitted Diseases - ID: D000016180 - Term: Lentivirus Infections - ID: D000012192 - Term: Retroviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000007153 - Term: Immunologic Deficiency Syndromes - ID: D000007154 - Term: Immune System Diseases - ID: D000012897 - Term: Slow Virus Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: LOW - As Found: Unknown - ID: M10199 - Name: Immunologic Deficiency Syndromes - Relevance: LOW - As Found: Unknown - ID: M3735 - Name: AIDS-Related Complex - Relevance: HIGH - As Found: AIDS-Related Complex - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M15558 - Name: Sexually Transmitted Diseases - Relevance: LOW - As Found: Unknown - ID: M17933 - Name: Sexually Transmitted Diseases, Viral - Relevance: LOW - As Found: Unknown - ID: M18640 - Name: Lentivirus Infections - Relevance: LOW - As Found: Unknown - ID: M15026 - Name: Retroviridae Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M15700 - Name: Slow Virus Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000386 - Term: AIDS-Related Complex ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000018894 - Term: Reverse Transcriptase Inhibitors - ID: D000019384 - Term: Nucleic Acid Synthesis Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000019380 - Term: Anti-HIV Agents - ID: D000044966 - Term: Anti-Retroviral Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17920 - Name: Zidovudine - Relevance: LOW - As Found: Unknown - ID: M18548 - Name: Didanosine - Relevance: LOW - As Found: Unknown - ID: M18546 - Name: Zalcitabine - Relevance: HIGH - As Found: Carcinoma in situ - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M20935 - Name: Reverse Transcriptase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M21350 - Name: Anti-HIV Agents - Relevance: LOW - As Found: Unknown - ID: M25428 - Name: Anti-Retroviral Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000016047 - Term: Zalcitabine ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02760979 **Brief Title:** The Efficacy of Denosumab in Decreasing Periprosthetic Bone Loss in Patients With Total Knee Arthroplasty **Official Title:** The Efficacy of Denosumab in Decreasing Periprosthetic Bone Loss in Patients With Total Knee Arthroplasty: A Randomised, Double Blind, Placebo Controlled Clinical Trial #### Organization Study ID Info **ID:** IIBSP-DEN-2012-24 #### Organization **Class:** OTHER **Full Name:** Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau #### Secondary ID Infos **ID:** 2012-001285-15 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2015-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-08-11 **Type:** ACTUAL **Last Update Submit Date:** 2017-08-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-01 **Type:** ACTUAL #### Start Date **Date:** 2013-01 **Status Verified Date:** 2017-08 #### Study First Post Date **Date:** 2016-05-04 **Type:** ESTIMATED **Study First Submit Date:** 2016-04-28 **Study First Submit QC Date:** 2016-05-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study evaluates the effect of Denosumab in decreasing the periprosthetic bone resorption after Total Knee Arthroplasty compared to placebo in 60 patients (30 placebo and 30 Denosumab) within a year after surgery. **Detailed Description:** Periprosthetic bone resorption after Total Knee Arthroplasty occurs as a consequence of prosthetic implant on the bone. Some of this patients (up to 13%) develop an aseptic failure of the prosthesis needing revision surgery. 2 groups of patients are treated with Placebo and Denosumab in a double blind prospective trial. Densitometry, Knee society score (KSS), Western Ontario McMaster University Osteoarthritis Index (WOMAC) and the Medical Outcomes Study Short Form 36 (SF-36) were done in both groups at 0,3,6 and 12 months after surgery. ### Conditions Module **Conditions:** - Bone Resorption **Keywords:** - knee arthroplasty ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients treated with Denosumab **Intervention Names:** - Drug: Denosumab **Label:** Denosumab **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Patients treated with placebo **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Denosumab **Description:** Denosumab treatment one year after surgery **Name:** Denosumab **Other Names:** - Prolia **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Serum one year after surgery **Name:** Placebo **Other Names:** - Serum **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Bone Mass index in gr/cm3 **Measure:** Change in Bone Mass index **Time Frame:** Change in densitometry before surgery (0) and at three (3) months after surgery **Description:** Bone Mass index in gr/cm3 **Measure:** Change in Bone Mass index **Time Frame:** Change in densitometry before surgery (0) and at six (6) months after surgery **Description:** Bone Mass index in gr/cm3 **Measure:** Change in Bone Mass index **Time Frame:** Change in densitometry before surgery (0) and at twelve (12) months after surgery #### Secondary Outcomes **Measure:** Quality of Life (WOMAC) **Time Frame:** WOMAC test before (0) and at three (3), six (6) and twelve (12) months after surgery **Measure:** Quality of life (SF-36) **Time Frame:** SF-36 test before (0) and at three (3), six (6) and twelve (12) months after surgery **Description:** Creatinine clearance **Measure:** Kidney function **Time Frame:** Before surgery and at three, six and twelve months after surgery **Description:** ALT, AST **Measure:** Liver function **Time Frame:** Before surgery and at three, six and twelve months after surgery **Description:** Beta cross lap and Procollagen type 1 n-terminal propeptide (P1NP) **Measure:** Bone turnover markers **Time Frame:** At three, six and twelve months after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with Knee Osteoarthritis treated with Total Knee Arthroplasty Exclusion Criteria: * Patients allergies to Denosumab * Patients with previous Osteoporosis treatment * Patients with renal failure * Patients with previous Bisphosphonate treatment for more than 5 years **Minimum Age:** 55 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Orthopaedic Department-Hospital de la Santa Creu i Sant Pau **Name:** Jose Carlos Gonzalez **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Ishii Y, Yagisawa K, Ikezawa Y. Changes in bone mineral density of the proximal femur after total knee arthroplasty. J Arthroplasty. 2000 Jun;15(4):519-22. doi: 10.1054/arth.2000.4639. **PMID:** 10884214 **Citation:** Sugita T, Umehara J, Sato K, Inoue H. Influence of tibial bone quality on loosening of the tibial component in total knee arthroplasty for rheumatoid arthritis: long-term results. Orthopedics. 1999 Feb;22(2):213-5. doi: 10.3928/0147-7447-19990201-10. **PMID:** 10037335 **Citation:** Wang CJ, Wang JW, Weng LH, Hsu CC, Huang CC, Chen HS. The effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty. J Bone Joint Surg Am. 2003 Nov;85(11):2121-6. doi: 10.2106/00004623-200311000-00009. **PMID:** 14630840 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5141 - Name: Bone Resorption - Relevance: HIGH - As Found: Bone Resorption - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001862 - Term: Bone Resorption ### Intervention Browse Module - Ancestors - ID: D000050071 - Term: Bone Density Conservation Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M417 - Name: Denosumab - Relevance: HIGH - As Found: 0.05 ### Intervention Browse Module - Meshes - ID: D000069448 - Term: Denosumab ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01622179 **Brief Title:** Outcome of Two Different Suture Methods for Achilles Tendon Rupture **Official Title:** Closed Achilles Tendon Rupture Treats by Two Different Suture Methods and the Outcome #### Organization Study ID Info **ID:** PLAGH OD 13 #### Organization **Class:** OTHER **Full Name:** Chinese PLA General Hospital ### Status Module #### Completion Date **Date:** 2013-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2013-02-20 **Type:** ESTIMATED **Last Update Submit Date:** 2013-02-19 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2013-05 **Type:** ESTIMATED #### Start Date **Date:** 2012-06 **Status Verified Date:** 2013-02 #### Study First Post Date **Date:** 2012-06-19 **Type:** ESTIMATED **Study First Submit Date:** 2012-06-05 **Study First Submit QC Date:** 2012-06-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Peifu Tang #### Responsible Party **Investigator Affiliation:** Chinese PLA General Hospital **Investigator Full Name:** Peifu Tang **Investigator Title:** Chief, Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to estimate the effective of two suture methods in the treatment of Achilles rupture. **Detailed Description:** Achilles tendon rupture is one of the most common tendon injuries in the adult population. The incidence of this injury is increasing as aging adults continue their participation in high-demand sports. Although the impact of an Achilles tendon rupture is substantial, often resulting in prolonged disability and rehabilitation. Studies have showed that the operation treatment of acute Achilles tendon ruptures had some advantages. But the rebuild of blood supply was not involved in previous studies. And the epitenon of tendon is the interior layer, closest to the endotenons which contains the vascular supply. Main difference of two suture methods were if the epitenon was repaired and sewed indirectly or unrepaired and sewed directly. ### Conditions Module **Conditions:** - Achilles Tendon Rupture **Keywords:** - surgery - suture method - blood supply ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The epitenon was repaired and sewed indirectly. **Intervention Names:** - Procedure: sewed indirectly **Label:** Indirectly **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The epitenon was unrepaired and sewed directly. **Intervention Names:** - Procedure: sewed directly **Label:** Directly **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Indirectly **Description:** The epitenon was repaired and sewed indirectly. **Name:** sewed indirectly **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Directly **Description:** The epitenon was unrepaired and sewed directly. **Name:** sewed directly **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Blood supply was estimated by ultrasonic contrast at six weeks after surgery. **Measure:** Blood supply condition **Time Frame:** six weeks #### Secondary Outcomes **Description:** Calf circumference was measured at six weeks after surgery. **Measure:** Calf circumference **Time Frame:** six weeks **Description:** Infection and rerupture at six month after surgery. **Measure:** Complications **Time Frame:** six months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult men or women between 18 and 60 years of age. * Closed rupture confirmed with ultrasound or magnetic resonance imaging (MRI). * Operative within 14 days after injury. * Willing and able to comply with and carry out the prescribed rehabilitation protocol. * Providing informed consent. * No other major trauma. Exclusion Criteria: * Refuse to participate. * Refuse to participate. * Additional ipsilateral injury. * Open injury. * Patients not suitable for surgery (i.e., mellitus diabetes, immunocompromised states, obesity (BMI.30), peripheral vascular disease or local/systemic dermatologic disorders) or have other surgical contraindications. * Fluoroquinolone-associated rupture (i.e., rupture within 2 weeks after taking this medication). * Achilles avulsion from the calcaneus or with bone fracture. * Neurological or vascular disease requiring medications recognized to impair tendon healing. **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Tang P Fu, Dr. **Phone:** 861099638101 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Zhang L Hai, Dr. **Phone:** 861099638102 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Tang P Fu, Dr. - **Phone:** 861099638101 - **Role:** CONTACT ***Contact 2:*** - **Name:** Zhang L Hai, Dr. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Orthopedics department; The General Hospital of the People's Liberation Army **State:** Beijing **Status:** RECRUITING **Zip:** 100853 #### Overall Officials **Official 1:** **Affiliation:** Chinese PLA General Hospital **Name:** Tang P Fu **Role:** STUDY_CHAIR ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2015-02-04 - Date Unknown: Unknown #### Event: RESET - Date: 2015-02-20 - Date Unknown: Unknown ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M15241 - Name: Rupture - Relevance: HIGH - As Found: Rupture - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012421 - Term: Rupture ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2015-02-04 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2015-02-04 - Reset Date: 2015-02-20 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04262479 **Acronym:** GADinLADA **Brief Title:** Injections of Glutamic Acid Decarboxylase (GAD) for LADA Type of Diabetes **Official Title:** A Pilot Study on Safety, Feasibility and Insulin-promotion by Intra-inguinal Lymph Node Injections of Glutamic Acid Decarboxylase (GAD) in Patients With LADA Type of Diabetes #### Organization Study ID Info **ID:** GADinLADA #### Organization **Class:** OTHER **Full Name:** Norwegian University of Science and Technology #### Secondary ID Infos **ID:** 2019-002692-34 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2022-05-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-05-26 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-05-05 **Type:** ACTUAL #### Start Date **Date:** 2020-03-02 **Type:** ACTUAL **Status Verified Date:** 2022-05 #### Study First Post Date **Date:** 2020-02-10 **Type:** ACTUAL **Study First Submit Date:** 2020-02-05 **Study First Submit QC Date:** 2020-02-06 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** St. Olavs Hospital **Class:** INDUSTRY **Name:** Diamyd Medical AB **Class:** OTHER **Name:** Karolinska Institutet **Class:** OTHER_GOV **Name:** Linkoeping University #### Lead Sponsor **Class:** OTHER **Name:** Norwegian University of Science and Technology #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study will evaluate the effects of 3 intra-nodal injections of GAD-alum (Diamyd), together with oral vitamin D supplementation. Safety and feasibility of the treatment will be evaluated and also effects on the immune system and on the preservation of endogenous insulin production. ### Conditions Module **Conditions:** - Latent Autoimmune Diabetes in Adults **Keywords:** - Glutamic Acid Decarboxylase - Alum Compounds - Injections - Inguinal Canal - Diamyd - rhGAD65 - Vitamin D ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 14 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart. Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total). **Intervention Names:** - Drug: recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel - Drug: Vitamin D **Label:** GAD-vaccination with vitamin D suppletion **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - GAD-vaccination with vitamin D suppletion **Description:** 3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden **Name:** recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel **Other Names:** - GAD-alum (Diamyd(R)) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - GAD-vaccination with vitamin D suppletion **Description:** 1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden **Name:** Vitamin D **Other Names:** - Divisun 2000 IE **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** skin reactions 1 hour post injection vs. before injection **Measure:** injection site skin reactions **Time Frame:** 1 hour **Description:** continuously monitored and registered **Measure:** Occurrence of adverse events (AEs) **Time Frame:** summarized at 5 months **Description:** continuously monitored and registered **Measure:** Occurrence of adverse events (AEs) **Time Frame:** summarized at 12 months **Description:** concentration in serum after the first injection vs baseline **Measure:** GAD65A titer in serum **Time Frame:** at 5 months **Description:** concentration in serum after the first injection vs baseline **Measure:** GAD65A titer in serum **Time Frame:** at 12 months #### Secondary Outcomes **Description:** measured by glucagon- and MMTT stimulated C-peptide **Measure:** Insulin secretion **Time Frame:** 5 months after first injection **Description:** measured by glucagon- and MMTT stimulated C-peptide **Measure:** insulin secretion **Time Frame:** 12 months after first injection **Measure:** Change in HbA1c **Time Frame:** from baseline to 5 and 12 months after the first injection **Measure:** Change in fasting glucose **Time Frame:** from baseline to 5 and 12 months after the first injection **Measure:** Change in Fasting C-peptide **Time Frame:** between baseline and 5 and 12 months after the first injection **Measure:** Change in maximum C-peptide during Mixed Meal Tolerance Test (MMTT) **Time Frame:** between baseline and 5 and 12 months after the first injection ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Signed informed consent by the patient. 2. Diagnosis of LADA and diabetes debut within the last 18 months before inclusion. LADA should be defined by the criteria of age ≥30 years at the onset of diabetes, anti-GAD positivity and no clinical need for permanent insulin treatment during the first 3 months after the diagnosis of diabetes. 3. Fasting C-peptid levels ≥ 0.3 nmol/l 4. High GADA titers (\>190 U/ml) 5. Patients must be insulin independent at baseline by clinical judgement and C-peptide criteria 6. Antidiabetic medication in the form of metformin is acceptable for inclusion as well as medications not mentioned under exclusion criteria 7. Females must agree to avoid pregnancy, and must have a negative urine pregnancy test. Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of GAD-alum. Adequate contraception is as follows: For females of childbearing potential: 1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives 2. combined (estrogen and progestogen containing) 3. oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation 4. intrauterine device 5. intrauterine hormone-releasing system (for example, progestin-releasing coil) 6. bilateral tubal occlusion 7. vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate) 8. male partner using condom 9. abstinence from heterosexual intercourse For males of childbearing potential: 1. condom (male) 2. abstinence from heterosexual intercourse Exclusion Criteria: 1. Current or previous treatment with immunosuppressant therapy (topical or inhaled steroids are accepted) 2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted) 3. Systemic treatment with glucocorticoids 4. Treatment with any vaccine, including influenza vaccine, within 1 month prior to planned first study drug dose or planned treatment with any vaccine up to 1 month after the last injection with study drug 5. Antidiabetic medication (metformin excepted) 6. Significantly abnormal hematology results at screening (i.e. anemia with hemoglobin \< 12 g/L). 7. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles 8. Clinically significant history of acute reaction to vaccines in the past. 9. Renal disease (as defined by serum creatinine \>150 µmol/l) 10. Serious cardiovascular events (myocardial infarction, stroke) within the last year preceding recruitment. 11. Participation in other clinical trials with a new chemical entity within the previous 3 months 12. A history of alcohol or drug abuse 13. Known HIV or hepatitis 14. Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study 15. Other serious chronic disease as judged by investigator. 16. Females who are lactating, are pregnant or intend to become pregnant. 17. Inability or unwillingness to comply with the provisions of this protocol 18. Deemed by the investigator not being able to follow instructions and/or follow the study protocol 19. Treatment any other supplementation of with vitamin D, marketed or not, or unwilling to abstain from such medication during the trial 120 days daily intake of Divisun (non-investigational medicinal product) **Maximum Age:** 70 Years **Minimum Age:** 30 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Trondheim **Country:** Norway **Facility:** Department of Endocrinology, St Olavs Hospital **Location 2:** **City:** Stockholm **Country:** Sweden **Facility:** Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute #### Overall Officials **Official 1:** **Affiliation:** St Olavs Hospital, Medisinsk Klinikk **Name:** Anne Hildur Henriksen, MD PhD **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Norwegian University of Science and Technology, IKOM **Name:** Torstein Baade Rø, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** There is not a plan to make IPD available. **IPD Sharing:** NO ### References Module #### References **Citation:** Hals IK, Fiskvik Fleiner H, Reimers N, Astor MC, Filipsson K, Ma Z, Grill V, Bjorklund A. Investigating optimal beta-cell-preserving treatment in latent autoimmune diabetes in adults: Results from a 21-month randomized trial. Diabetes Obes Metab. 2019 Oct;21(10):2219-2227. doi: 10.1111/dom.13797. Epub 2019 Jun 19. **PMID:** 31148332 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M849 - Name: Latent Autoimmune Diabetes in Adults - Relevance: HIGH - As Found: Latent Autoimmune Diabetes in Adults - ID: M7117 - Name: Diabetes Mellitus, Type 1 - Relevance: HIGH - As Found: Autoimmune Diabetes - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003922 - Term: Diabetes Mellitus, Type 1 - ID: D000071698 - Term: Latent Autoimmune Diabetes in Adults ### Intervention Browse Module - Ancestors - ID: D000014815 - Term: Vitamins - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000050071 - Term: Bone Density Conservation Agents ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: Vi - Name: Vitamins - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown - ID: M17550 - Name: Vitamin D - Relevance: HIGH - As Found: Ultrasound - ID: M6003 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M257732 - Name: Aluminum sulfate - Relevance: LOW - As Found: Unknown - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: T442 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: T479 - Name: Vitamin D3 - Relevance: LOW - As Found: Unknown - ID: T440 - Name: Calciferol - Relevance: LOW - As Found: Unknown - ID: T5 - Name: Glutamic Acid - Relevance: HIGH - As Found: Implantable Cardioverter Defibrillator ### Intervention Browse Module - Meshes - ID: D000014807 - Term: Vitamin D ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01485679 **Brief Title:** 18 Fluoro-deoxy-glucose Positrons Emission Tomography Combined With Computed Tomography (18-FDG TEP-CT ) in the Diagnosis of the Degeneration of Intraductal Papillary Mucinous Tumor of the Pancreas **Official Title:** Evaluation of 18 Fluoro-deoxy-glucose Positrons Emission Tomography Combined With Computed Tomography (18-FDG TEP-CT ) in the Diagnosis of the Degeneration of Intraductal Papillary Mucinous Tumor of the Pancreas #### Organization Study ID Info **ID:** BRD/10/06-P #### Organization **Class:** OTHER **Full Name:** Nantes University Hospital ### Status Module #### Completion Date **Date:** 2015-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-05-18 **Type:** ESTIMATED **Last Update Submit Date:** 2016-05-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-04 **Type:** ACTUAL #### Start Date **Date:** 2011-01 **Status Verified Date:** 2015-10 #### Study First Post Date **Date:** 2011-12-05 **Type:** ESTIMATED **Study First Submit Date:** 2011-08-26 **Study First Submit QC Date:** 2011-12-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nantes University Hospital #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** The aim of the study is to evaluate whether the TEP-CT can be sensitive and specific in identifying degenerated intraductal papillary mucinous tumor of the pancreas.The results will be compared to those obtained by the pathological analysis of the removed piece of pancreas. **Detailed Description:** Before surgery is undertaken, a 18 fluoro-deoxy-glucose positrons emission tomography combined with computed tomography (18-FDG TEP-CT ) will be performed. The primary outcome of this study is to compare results of the TEP-CT with those obtained by the pathological analysis of the removed piece of pancreas. ### Conditions Module **Conditions:** - Tumor **Keywords:** - 18 fluoro deoxy glucose positrons emission tomography combined with computed tomography, - Patients with intraductal papillary mucinous tumor of the pancreas - intraductal papillary mucinous - pancreas ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 126 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Other: 18 fluoro-deoxy-glucose positrons emission tomography combined with computed tomography **Label:** positrons emission tomography **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - positrons emission tomography **Description:** 18 fluoro-deoxy-glucose positrons emission tomography combined with computed tomography **Name:** 18 fluoro-deoxy-glucose positrons emission tomography combined with computed tomography **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** TEP-CT of the different 5 parts of the pancreas (head, uncus, isthmi, body and tail) will be interpreted by nuclearity Doctors. TEP-CT will be considered positive if there is a pathological fixation of the 18-FDG , defined as any focal or diffuse fixation of 18-FDG above the background level of fixation in the pancreas. The anatomopathological analysis of the piece of pancreas removed during the ablative surgery will be considered as positive if the degree of dysplasia seen for each part of the pancreas is "infiltrating carcinoma". Results will then be compared in term of specificity. **Measure:** Specificity of TEP-CT to point out malignant lesions in pancreas, the gold standard being the anatomopathological analysis of the piece of pancreas removed during the surgery. **Time Frame:** 3 months #### Secondary Outcomes **Description:** TEP-CT of the different 5 parts of the pancreas (head, uncus, isthmi, body and tail) will be interpreted by nuclearity Doctors. TEP-CT will be considered positive if there is a pathological fixation of the 18-FDG , defined as any focal or diffuse fixation of 18-FDG above the background level of fixation in the pancreas. The anatomopathological analysis of the piece of pancreas removed during the ablative surgery will be considered as positive if the degree of dysplasia seen for each part of the pancreas is "infiltrating carcinoma". Results will then be compared in term of sensitivity. **Measure:** Sensitivity of TEP-CT to point out malignant lesions in pancreas, the gold standard being the anatomopathological analysis of the piece of pancreas removed during the surgery. **Time Frame:** 3 months **Description:** Result of conventional devices (such as computed tomography, magnetic resonance cholangiopancreatography or endoscopic ultrasound) will be considered positive if diagnosis is "malignant lesion" or "probable malignant lesion". The 5 parts of the pancreas will be examined. **Measure:** Comparison of specificity of the TEP-CT to detect malignant lesions in pancreas versus specificity of conventional devices, the gold standard being the anatomopathological analysis results **Time Frame:** 3 months **Measure:** Number of patients for which metastasis will be detected through TEP-CT and confirmed by biopsy and/or conventional specific device **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults with age equal or above 18 * Patients diagnosed with intraductal papillary mucinous tumor with surgical indication and for whom it will be possible to have the pathological analysis of the removed piece of pancreas. * if woman being of childbearing potential, woman taking contraceptive measures * Patient able to understand benefits and risks of protocol * Subject affiliated to French health insurance (Social Security) * Informed consent form signed Exclusion Criteria: * Patients not fulfilling inclusion criteria * Pancreatic surgery or radiotherapy in the pancreatic zone within 4 the months preceding the TEP-CT * Chemotherapy within 2 the months preceding the TEP-CT * Acute pancreatitis within 2 the months preceding the TEP-CT * Pregnant women or breast-feeding women refusing to temporary stop it * Diabetes not equilibrated (checked by glycemia and glycosylated hemoglobin (HbA1c) at inclusion) or Fasting blood glucose below 7mmol/L (126 g/L before the TEP) * Patients with claustrophobia * Patients not accepted under the anesthesia point of view **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Amiens **Country:** France **Facility:** CHU Nord **Zip:** 80080 **Location 2:** **City:** Bordeaux **Country:** France **Facility:** Maison de Haut Lévêque CHU **Zip:** 33604 **Location 3:** **City:** Clichy **Country:** France **Facility:** Hôpital Beaujon APHP **Zip:** 92110 **Location 4:** **City:** Lille **Country:** France **Facility:** Hôpital C Huriez **Zip:** 59037 **Location 5:** **City:** Lyon **Country:** France **Facility:** Hospices Civils de Lyon **Zip:** 69437 **Location 6:** **City:** Marseille **Country:** France **Facility:** Institut Paoli Calmettes **Zip:** 13273 **Location 7:** **City:** Marseille **Country:** France **Facility:** CHU Nord **Zip:** 13915 **Location 8:** **City:** Nantes **Country:** France **Facility:** CHU **Zip:** 44093 **Location 9:** **City:** Paris **Country:** France **Facility:** Hôpital St-Antoine **Zip:** 75012 **Location 10:** **City:** Rennes **Country:** France **Facility:** CHU Hôpital Pontchaillou **Zip:** 35033 **Location 11:** **City:** Strasbourg **Country:** France **Facility:** Hôpital de Hautepierre **Zip:** 67098 **Location 12:** **City:** Toulouse **Country:** France **Facility:** CHU Rangueil **Zip:** 31059 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000010182 - Term: Pancreatic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13110 - Name: Pancreatic Neoplasms - Relevance: HIGH - As Found: Tumors of the Pancreas - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M13102 - Name: Pancreatic Diseases - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: T4387 - Name: Pancreatic Cancer - Relevance: HIGH - As Found: Tumors of the Pancreas ### Condition Browse Module - Meshes - ID: D000010190 - Term: Pancreatic Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M21686 - Name: Fluorodeoxyglucose F18 - Relevance: LOW - As Found: Unknown - ID: M7043 - Name: Deoxyglucose - Relevance: HIGH - As Found: Velban - ID: M22554 - Name: Pancrelipase - Relevance: LOW - As Found: Unknown - ID: M13114 - Name: Pancreatin - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003847 - Term: Deoxyglucose ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05744479 **Acronym:** METIDD **Brief Title:** Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability **Official Title:** Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability: A Double-Blind Randomized Control Trial #### Organization Study ID Info **ID:** 024/2022 #### Organization **Class:** OTHER **Full Name:** Centre for Addiction and Mental Health ### Status Module #### Completion Date **Date:** 2026-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-16 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-11 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-12-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-02-28 **Type:** ACTUAL **Status Verified Date:** 2023-02 #### Study First Post Date **Date:** 2023-02-27 **Type:** ACTUAL **Study First Submit Date:** 2023-01-13 **Study First Submit QC Date:** 2023-02-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centre for Addiction and Mental Health #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** People with IDD (intellectual and developmental disability) have very high rates of obesity and die prematurely from cardiometabolic disease. While antipsychotics contribute to this problem, their use is necessary and appropriate in a significant subgroup of individuals with IDD. Exercise and diet interventions have limitations and may not be sufficient, requiring effective adjunctive pharmacological approaches to target obesity and related comorbidities in IDD. However, persons with IDD treated with antipsychotics are systematically excluded from clinical trials hindering development of evidence to help guide safe and effective treatment of these comorbidities. Moreover, evidence from other disorders cannot be extrapolated to IDD given inherent biological differences between disorders. This trial will address the identified gaps, which extend beyond cardiovascular morbidity and negatively impact psychosocial outcomes, in a hugely underserviced population.This is the the first RCT (randomized control trial) to examine the efficacy of metformin in overweight or obese adults with IDD who have experienced antipsychotic-induced weight gain. By generating efficacy data for a very accessible and scalable intervention, allows for guideline and implementation strategies to address a recalcitrant health problem. ### Conditions Module **Conditions:** - Intellectual Disability - Developmental Disability - Obesity **Keywords:** - Intellectual Disability - Developmental Disability - Obesity - Metformin ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Metformin vs Placebo ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** Double Blinded RCT **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 50 participants will be administered oral metformin titrated to a maximum dose of 2000mg/day for 24 weeks. **Intervention Names:** - Drug: Metformin - Behavioral: Lifestyle Intervention **Label:** Metformin (Oral) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 50 participants will be administered an identical oral placebo for 24 weeks. **Intervention Names:** - Drug: Placebo - Behavioral: Lifestyle Intervention **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Metformin (Oral) **Description:** Metformin oral, 2000mg/day, for 24 weeks. **Name:** Metformin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Oral placebo for 24 weeks **Name:** Placebo **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Metformin (Oral) - Placebo **Description:** Participants from both groups will meet a dietician and a diabetes educator at the study start to obtain advice regarding healthy diet, portion size, and meal planning to improve physical health. All participants will be invited to monthly group meetings to learn skills which will help them in a variety of wellness areas such as physical exercises and diet. Attendance in these sessions will be encouraged but not mandatory, and attendance will be recorded. Fidelity with these interventions will be captured using diet and physical activity questionnaires at RCT start, midpoint and end, and end of open label phase. **Name:** Lifestyle Intervention **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Percentage change in body weight measured in percentage change of pounds (lbs) **Measure:** Individual's percentage change in body weight **Time Frame:** Weeks 0, 4, 8, 12, 16, 10, 24 #### Secondary Outcomes **Description:** Percentage change in body weight measured in percentage change of pounds (lbs), expressed as a percentage **Measure:** Proportion of participants who achieve body weight reduction ≥5%, and ≥10% in each arm **Time Frame:** Week 0 and week 24 **Description:** Absolute change in body weight between metformin and placebo groups measured in pounds (lbs). Calculated by the mean change in weight between the metformin and placebo groups. **Measure:** Between group (metformin vs placebo) absolute change in weight **Time Frame:** Week 24 **Description:** Absolute change in waist circumstance measured in centimetres (cm) between metformin and placebo groups. Calculated by the mean change in waist circumstance between the metformin and placebo groups. **Measure:** Between group absolute change in waist circumference **Time Frame:** Week 24 **Description:** Absolute change in BMI between metformin and placebo groups. Calculated by the mean change in BMI between the metformin and placebo groups. **Measure:** Between group absolute change in BMI **Time Frame:** Week 24 **Description:** With the results of the oral glucose tolerance test at Week 0 and Week 24, insulin sensitivity was calculated with the Matsuda index. Insulin sensitivity was calculated with Matsuda index: \[10,000 / √glucose minute 0 x insulin minute 0) (mean glucose (OGTT) x mean insulin OGTT)\]. A higher result is better. In the formula OGTT: oral glucose tolerance test. **Measure:** Change in whole body insulin sensitivity calculated with Matsuda Index **Time Frame:** Week 0 and Week 24 **Description:** ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index. **Measure:** Change in beta-cell function, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2) **Time Frame:** Week 0 and Week 24 **Description:** Measured through the change in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) derived from the Oral Glucose Tolerance Test (OGTT). **Measure:** Proportion in each group converting to impaired glucose tolerance, prediabetes, or type 2 diabetes **Time Frame:** Week 0 and Week 24 **Description:** Measured through the change in C-reactive protein (CRP) assessed at week 0 and week 24. Healthy levels: CRP: Less than 0.3 mg/dL **Measure:** Change in cardiovascular risk factors assessed by change in C-reactive protein **Time Frame:** Week 0 and Week 24 **Description:** Change in fasting lipid profile (low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglycerides) assessed at week 0 and week 24. Healthy levels: LDL: less than 100mg/dL HDL: 40mg/dL or higher Triglycerides: less than 150mg/dL **Measure:** Change in cardiovascular risk factor assessed by change in fasting lipids profile **Time Frame:** Week 0 and Week 24 **Description:** Measured through the change in blood pressure (systolic/diastolic) assessed at week 0 and week 24. A blood pressure range of 110/70 to 120/80 is considered normal. **Measure:** Change in cardiovascular risk factor assessed by change in blood pressure **Time Frame:** Week 0 and Week 24 **Description:** Change in visceral and liver fat content assessed via MRI scans at week 0 and week 24. **Measure:** Change in visceral and liver fat content **Time Frame:** Week 0 and Week 24 **Description:** Measured through returning of blister pill packs, and assessing number of pills taken. **Measure:** Medication Adherence **Time Frame:** Week 0 to Week 24 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Stable outpatients * Age 18-65 years * Diagnosed with IDD * On maintenance treatment with an antipsychotic (stable dose for ≥3 months). * BMI must be ≥30 kg/m2, or ≥27 kg/m2 with at least one weight-related comorbidity (treated or untreated) such as: hypertension, dyslipidaemia, obstructive sleep apnea, or impaired fasting glucose. * Females of child-bearing age must be on one of the following regular contraceptives: 1. Agree to abstain from sex for the duration of the trial or 2. A barrier method of a diaphragm with spermicide and/or Latex condom or 3. An oral contraceptive agent, implantable contraceptive or an injectable contraceptive for at least six months prior to entering the study and will continue its use throughout the study, or 4. An intrauterine device, or 5. Partner has had a vasectomy at least 3 months prior to study start Exclusion Criteria: * Females who are nursing, currently pregnant, or have a positive pregnancy test * Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, haematological, hepatic, renal, or pulmonary disease * Previous treatment and lack of efficacy or tolerability with metformin * History or diagnosis of Type 1 Diabetes (T1D) or Type 2 Diabetes (TD2) or fasting blood work, HbA1c \> 6.5% * History of metabolic acidosis or lactic acidosis * Treatment with weight-lowering agents * Medications with significant renal impact * Major medical or surgical event in the preceding 3 months * Acute suicidal risk. * Moderate to severe substance use disorder, other than caffein or nicotine use disorder **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mahavir Agarwal, MD, PhD **Phone:** 4165358501 **Phone Ext:** 30546 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Maria Papoulias **Phone:** 4165358501 **Phone Ext:** 39365 **Role:** CONTACT #### Locations **Location 1:** **City:** Toronto **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Maria Papoulias, MSc - **Phone:** 416-535-8501 - **Role:** CONTACT ***Contact 2:*** - **Name:** Mahavir Agarwal, PhD, MBBS, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** Centre for Addiction and Mental Health **State:** Ontario **Status:** RECRUITING **Zip:** M6J1H3 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001835 - Term: Body Weight - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000001836 - Term: Body Weight Changes - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000065886 - Term: Neurodevelopmental Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M5902 - Name: Developmental Disabilities - Relevance: HIGH - As Found: Developmental Disabilities - ID: M11589 - Name: Intellectual Disability - Relevance: HIGH - As Found: Intellectual Disability - ID: M18101 - Name: Weight Gain - Relevance: HIGH - As Found: Weight Gain - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M5115 - Name: Body Weight Changes - Relevance: LOW - As Found: Unknown - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown - ID: M30644 - Name: Neurodevelopmental Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008607 - Term: Intellectual Disability - ID: D000015430 - Term: Weight Gain - ID: D000002658 - Term: Developmental Disabilities ### Intervention Browse Module - Ancestors - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: PsychDr - Name: Psychotropic Drugs ### Intervention Browse Module - Browse Leaves - ID: M11667 - Name: Metformin - Relevance: HIGH - As Found: Assessment - ID: M16904 - Name: Antipsychotic Agents - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008687 - Term: Metformin ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05557279 **Brief Title:** Urinary Microbiome Changes Following Administration of 500 mg of NDS-446 in Women With Dry OAB at 12 Weeks **Official Title:** Urinary Microbiome Changes Following Administration of 500 mg of NDS-446 in Women With Dry OAB at 12 Weeks - a Single-center Study #### Organization Study ID Info **ID:** 215838 #### Organization **Class:** OTHER **Full Name:** Loyola University ### Status Module #### Completion Date **Date:** 2024-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-11 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-08 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-04-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-01-01 **Type:** ACTUAL **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2022-09-28 **Type:** ACTUAL **Study First Submit Date:** 2022-09-12 **Study First Submit QC Date:** 2022-09-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Loyola University #### Responsible Party **Investigator Affiliation:** Loyola University **Investigator Full Name:** Elizabeth Mueller MD **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to learn about how the use of 500 mg of dried cranberry powder extract (NDS-446) changes the bacteria that normal reside in the bladder of women who don't have urinary leakage problems but do have problems with urinary urgency and frequency. **Detailed Description:** While this treatment algorithm is the recommended approach to OAB management, recent research has resulted in the development of a new paradigm that may influence how this condition is treated in the future. This research focuses on the urinary microbiome and for a decade it has been known that urine is not sterile. Expanded Quantitative Urine Culture (EQUC) techniques have allowed for more comprehensive and accurate 16S ribosomal RNA sequencing of the urinary microbiome. Changes in the abundance and diversity of the resident microbiota have been associated with a number of urogenital conditions including interstitial cystitis, urinary incontinence, responses to OAB medications and symptoms of urinary tract infections. These studies provide insight to the fact that the microbiome plays an important role in the maintenance of a healthy urogenital tract. Thus, treatments that target the microbiome for one condition may work for others by similar mechanisms, especially when there is considerable symptom overlap between the two conditions as there is in UTIs and OAB. One such treatment is cranberry (Vaccinium macrocarpon) extract, which has long been used as complementary therapy for a variety of medical conditions. Health benefits are linked to the presence of phytochemicals present in the fruit- anthocyanins, flavonols, tannins, proanthocyanidins, and phenolic acid derivatives. Cranberry is known to be effective in the prevention of UTIs. In a recent study examining its use in women with dry OAB, daily dried cranberry improved urgency symptoms and number of daytime voids. In addition, the authors reported an improvement in the validated subjective instrument, Patient Perception of Bladder Condition (PPBC). Moderately symptomatic LUTS in men improved following 6 months of daily dried cranberry powder. Therefore, the investigators aim to investigate changes to the female urinary microbiome in women with dry OAB who take daily dried cranberry extract. This study aims to quantify a change in urinary frequency, urinary urgency, and PPBC following the daily use of a cranberry extract called NDS-446. The investigators also have an ancillary hypothesis that women who are post-menopausal will develop a urinary microbiome more similar to pre-menopausal women by the end of the study. Lastly, the investigators will measure the levels of extracellular (eATP) in the urine of participants. It has been previously shown that higher levels of eATP are associated with worsening OAB symptoms. ### Conditions Module **Conditions:** - Overactive Bladder ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** All participants will receive 500 mg NDS-446 daily for 12 weeks following a baseline assessment and meeting inclusion/exclusion criteria 20 premenopausal women, 20 postmenopausal women not on estrogen supplementation ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All participants will receive 500 mg NDS-446 daily for 12 weeks **Intervention Names:** - Drug: 500 mg NDS-446 **Label:** Intervention Group **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention Group **Description:** All participants will receive 500 mg NDS-446 daily for 12 weeks following a baseline assessment **Name:** 500 mg NDS-446 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Vaginal and peri-urethral swabs, as well as voided and catheterized urine specimens, will be obtained. **Measure:** Compare the UG microbiota (vagina, peri-urethral, catheterized and voided urine) of female participants with urgency-frequency syndrome after 12 weeks of daily use of 500 mg of NDS-446 to the UG microbiota at baseline. **Time Frame:** 12 week visit #### Secondary Outcomes **Description:** The Patient Perception of Bladder Condition (PPBC) score in the study participants. **Measure:** Compare the baseline and 12 week PPBC score in pre-menopausal and post-menopausal who take 500 mg of NDS-446 daily. **Time Frame:** 12 week visit ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 18 years, female, ambulatory * OAB symptoms \> 6 months * Voiding frequency \> 8 times in 24 hrs and \> 3 episodes of urgency (grade 3 or 4) without incontinence during 3-day diary at baseline Exclusion Criteria: * Self-reported urinary incontinence (\> 3 episodes in the month prior) * UTI \> 3 in last 12 months * A diagnosis of painful bladder syndrome or interstitial cystitis * LUT surgery last 6 months * Drug or non-drug treatment of OAB (previous 60 days) or current meds that affect detrusor activity * On Warfarin * Failure to complete 3-day diary * Aspirin \> 81 mg daily * Gross hematuria * Allergy or sensitivity to aspirin * Subjects taking anti-platelet agents * Inability to swallow capsules **Maximum Age:** 99 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mary Tulke, RN **Phone:** 708-216-2186 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Elizabeth Mueller, MD **Phone:** 708-216-2170 **Role:** CONTACT #### Locations **Location 1:** **City:** Maywood **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mary Tulke, RN - **Phone:** 708-216-2067 - **Role:** CONTACT **Country:** United States **Facility:** Loyola Medical Center **State:** Illinois **Status:** RECRUITING **Zip:** 60153 #### Overall Officials **Official 1:** **Affiliation:** Loyola Medical Center **Name:** Elizabeth Mueller, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN; International Urogynecological Association; International Continence Society. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29(1):4-20. doi: 10.1002/nau.20798. **PMID:** 19941278 **Citation:** Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, Van Kerrebroeck P, Victor A, Wein A; Standardisation Sub-Committee of the International Continence Society. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003 Jan;61(1):37-49. doi: 10.1016/s0090-4295(02)02243-4. No abstract available. **PMID:** 12559262 **Citation:** Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003 May;20(6):327-36. doi: 10.1007/s00345-002-0301-4. Epub 2002 Nov 15. **PMID:** 12811491 **Citation:** Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, Coyne K, Kelleher C, Hampel C, Artibani W, Abrams P. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006 Dec;50(6):1306-14; discussion 1314-5. doi: 10.1016/j.eururo.2006.09.019. Epub 2006 Oct 2. **PMID:** 17049716 **Citation:** Milsom I, Kaplan SA, Coyne KS, Sexton CC, Kopp ZS. Effect of bothersome overactive bladder symptoms on health-related quality of life, anxiety, depression, and treatment seeking in the United States: results from EpiLUTS. Urology. 2012 Jul;80(1):90-6. doi: 10.1016/j.urology.2012.04.004. **PMID:** 22748867 **Citation:** Gormley EA, Lightner DJ, Faraday M, Vasavada SP; American Urological Association; Society of Urodynamics, Female Pelvic Medicine. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol. 2015 May;193(5):1572-80. doi: 10.1016/j.juro.2015.01.087. Epub 2015 Jan 23. **PMID:** 25623739 **Citation:** Madhuvrata P, Cody JD, Ellis G, Herbison GP, Hay-Smith EJ. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev. 2012 Jan 18;1:CD005429. doi: 10.1002/14651858.CD005429.pub2. **PMID:** 22258963 **Citation:** Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. 2019 Aug 1;179(8):1084-1093. doi: 10.1001/jamainternmed.2019.0677. **PMID:** 31233095 **Citation:** Chapple CR, Nazir J, Hakimi Z, Bowditch S, Fatoye F, Guelfucci F, Khemiri A, Siddiqui E, Wagg A. Persistence and Adherence with Mirabegron versus Antimuscarinic Agents in Patients with Overactive Bladder: A Retrospective Observational Study in UK Clinical Practice. Eur Urol. 2017 Sep;72(3):389-399. doi: 10.1016/j.eururo.2017.01.037. Epub 2017 Feb 11. **PMID:** 28196724 **Citation:** Wolfe AJ, Toh E, Shibata N, Rong R, Kenton K, Fitzgerald M, Mueller ER, Schreckenberger P, Dong Q, Nelson DE, Brubaker L. Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol. 2012 Apr;50(4):1376-83. doi: 10.1128/JCM.05852-11. Epub 2012 Jan 25. **PMID:** 22278835 **Citation:** Siddiqui H, Nederbragt AJ, Lagesen K, Jeansson SL, Jakobsen KS. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011 Nov 2;11:244. doi: 10.1186/1471-2180-11-244. **PMID:** 22047020 **Citation:** Price TK, Dune T, Hilt EE, Thomas-White KJ, Kliethermes S, Brincat C, Brubaker L, Wolfe AJ, Mueller ER, Schreckenberger PC. The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms. J Clin Microbiol. 2016 May;54(5):1216-22. doi: 10.1128/JCM.00044-16. Epub 2016 Mar 9. **PMID:** 26962083 **Citation:** Brubaker L, Nager CW, Richter HE, Visco A, Nygaard I, Barber MD, Schaffer J, Meikle S, Wallace D, Shibata N, Wolfe AJ. Urinary bacteria in adult women with urgency urinary incontinence. Int Urogynecol J. 2014 Sep;25(9):1179-84. doi: 10.1007/s00192-013-2325-2. Epub 2014 Feb 11. **PMID:** 24515544 **Citation:** Burnett LA, Hochstedler BR, Weldon K, Wolfe AJ, Brubaker L. Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women. Neurourol Urodyn. 2021 Aug;40(6):1479-1489. doi: 10.1002/nau.24707. Epub 2021 May 26. **PMID:** 34036621 **Citation:** Pearce MM, Zilliox MJ, Rosenfeld AB, Thomas-White KJ, Richter HE, Nager CW, Visco AG, Nygaard IE, Barber MD, Schaffer J, Moalli P, Sung VW, Smith AL, Rogers R, Nolen TL, Wallace D, Meikle SF, Gai X, Wolfe AJ, Brubaker L; Pelvic Floor Disorders Network. The female urinary microbiome in urgency urinary incontinence. Am J Obstet Gynecol. 2015 Sep;213(3):347.e1-11. doi: 10.1016/j.ajog.2015.07.009. Epub 2015 Jul 23. **PMID:** 26210757 **Citation:** Thomas-White KJ, Hilt EE, Fok C, Pearce MM, Mueller ER, Kliethermes S, Jacobs K, Zilliox MJ, Brincat C, Price TK, Kuffel G, Schreckenberger P, Gai X, Brubaker L, Wolfe AJ. Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J. 2016 May;27(5):723-33. doi: 10.1007/s00192-015-2847-x. Epub 2015 Sep 30. **PMID:** 26423260 **Citation:** Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD001321. doi: 10.1002/14651858.CD001321.pub5. **PMID:** 23076891 **Citation:** Cho A, Eidelberg A, Butler DJ, Danko D, Afshinnekoo E, Mason CE, Chughtai B. Efficacy of Daily Intake of Dried Cranberry 500 mg in Women with Overactive Bladder: A Randomized, Double-Blind, Placebo Controlled Study. J Urol. 2021 Feb;205(2):507-513. doi: 10.1097/JU.0000000000001384. Epub 2020 Sep 18. **PMID:** 32945735 **Citation:** Vidlar A, Student V Jr, Vostalova J, Fromentin E, Roller M, Simanek V, Student V. Cranberry fruit powder (Flowens) improves lower urinary tract symptoms in men: a double-blind, randomized, placebo-controlled study. World J Urol. 2016 Mar;34(3):419-24. doi: 10.1007/s00345-015-1611-7. Epub 2015 Jun 7. **PMID:** 26049866 **Citation:** Vidlar A, Vostalova J, Ulrichova J, Student V, Stejskal D, Reichenbach R, Vrbkova J, Ruzicka F, Simanek V. The effectiveness of dried cranberries ( Vaccinium macrocarpon) in men with lower urinary tract symptoms. Br J Nutr. 2010 Oct;104(8):1181-9. doi: 10.1017/S0007114510002059. Epub 2010 Aug 31. **PMID:** 20804630 **Citation:** Silva-Ramos M, Silva I, Oliveira O, Ferreira S, Reis MJ, Oliveira JC, Correia-de-Sa P. Urinary ATP may be a dynamic biomarker of detrusor overactivity in women with overactive bladder syndrome. PLoS One. 2013 May 31;8(5):e64696. doi: 10.1371/journal.pone.0064696. Print 2013. **PMID:** 23741373 **Citation:** Thomas-White K, Taege S, Limeira R, Brincat C, Joyce C, Hilt EE, Mac-Daniel L, Radek KA, Brubaker L, Mueller ER, Wolfe AJ. Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms. Am J Obstet Gynecol. 2020 Nov;223(5):727.e1-727.e11. doi: 10.1016/j.ajog.2020.08.006. Epub 2020 Aug 11. **PMID:** 32791124 **Citation:** Price TK, Wolff B, Halverson T, Limeira R, Brubaker L, Dong Q, Mueller ER, Wolfe AJ. Temporal Dynamics of the Adult Female Lower Urinary Tract Microbiota. mBio. 2020 Apr 21;11(2):e00475-20. doi: 10.1128/mBio.00475-20. **PMID:** 32317321 **Citation:** Coyne KS, Matza LS, Kopp Z, Abrams P. The validation of the patient perception of bladder condition (PPBC): a single-item global measure for patients with overactive bladder. Eur Urol. 2006 Jun;49(6):1079-86. doi: 10.1016/j.eururo.2006.01.007. Epub 2006 Jan 24. **PMID:** 16460875 **Citation:** Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016 Jul;13(7):581-3. doi: 10.1038/nmeth.3869. Epub 2016 May 23. **PMID:** 27214047 **Citation:** Gao X, Lin H, Revanna K, Dong Q. A Bayesian taxonomic classification method for 16S rRNA gene sequences with improved species-level accuracy. BMC Bioinformatics. 2017 May 10;18(1):247. doi: 10.1186/s12859-017-1670-4. **PMID:** 28486927 **Citation:** McMurdie PJ, Holmes S. Phyloseq: a bioconductor package for handling and analysis of high-throughput phylogenetic sequence data. Pac Symp Biocomput. 2012:235-46. **PMID:** 22174279 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001745 - Term: Urinary Bladder Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000059411 - Term: Lower Urinary Tract Symptoms - ID: D000020924 - Term: Urological Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M27167 - Name: Urinary Bladder, Overactive - Relevance: HIGH - As Found: Overactive Bladder - ID: M5026 - Name: Urinary Bladder Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M29464 - Name: Lower Urinary Tract Symptoms - Relevance: LOW - As Found: Unknown - ID: M22659 - Name: Urological Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000053201 - Term: Urinary Bladder, Overactive ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04465279 **Brief Title:** Trifocal Diffractive Intraocular Lens After Cataract Extraction With Phacoemulsification **Official Title:** Evaluation of Trifocal Diffractive Intraocular Lens After Cataract Extraction With Phacoemulsification #### Organization Study ID Info **ID:** 0000755 #### Organization **Class:** OTHER **Full Name:** Alexandria University ### Status Module #### Completion Date **Date:** 2020-06-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-07-10 **Type:** ACTUAL **Last Update Submit Date:** 2020-07-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-05-15 **Type:** ACTUAL #### Start Date **Date:** 2018-10-15 **Type:** ACTUAL **Status Verified Date:** 2020-06 #### Study First Post Date **Date:** 2020-07-10 **Type:** ACTUAL **Study First Submit Date:** 2020-06-28 **Study First Submit QC Date:** 2020-07-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Alexandria University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Multifocal IOLs that maintain distance focus and improve near vision have been developed to reduce spectacle dependence.Multifocal IOLs improve patient performance of near-vision tasks, such as reading crafts, hobbies, and social activities to a greater extent than do monofocal IOLs. However, halos and reduced contrast sensitivity have been associated with multifocal IOLs and are common reasons for patient's dissatisfaction.Trifocal technology has been developed to create intermediate focus to overcome these difficulties. Continuous reports of the visual outcomes of the FineVision trifocal IOLs are encouraging. **Detailed Description:** Monofocal IOLs, which provide effective distance vision, currently account for the majority of IOLs implantations. Patients who have undergone cataract surgery with implantation of monofocal IOL may require spectacles to perform near-distance (e.g., reading) or intermediate-distance (e.g., using a computer) tasks depending on their visual demandsMultifocal IOLs that maintain distance focus and improve near vision have been developed to reduce spectacle dependence.Multifocal IOLs improve patient performance of near-vision tasks, such as reading crafts, hobbies, and social activities to a greater extent than do monofocal IOLs. However, halos and reduced contrast sensitivity have been associated with multifocal IOLs and are common reasons for patient's dissatisfaction.Trifocal technology has been developed to create intermediate focus to overcome these difficulties. Continuous reports of the visual outcomes of the FineVision trifocal IOLs are encouraging. ### Conditions Module **Conditions:** - Refractive Errors ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** This is a prospective, non-comparative, non-randomized study including 36 eyes had implantation of trifocal diffractive IOL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 36 **Type:** ACTUAL **Phases:** - PHASE2 - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 36 eyes having implantation of trifocal diffractive IOL (FineVision) **Intervention Names:** - Device: Trifocal diffractive intraocular lens **Label:** Trifocal Diffractive Intraocular Lens (FineVision) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Trifocal Diffractive Intraocular Lens (FineVision) **Description:** Trifocal IOL having foldable single-piece fully diffractive pupil dependent aspheric IOL. Which have been made of hydrophilic acrylic with an ultraviolet (UV) and blue light inhibitor. It has an optic diameter of 6.15 mm and an overall diameter of 10.75 mm; it has +3.5D additional power for near vision and +1.75 D additional power for intermediate vision, consisting of 26 diffractive steps. **Name:** Trifocal diffractive intraocular lens **Other Names:** - (FineVision IOL) **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Current study used Sloan chart (Good - Lite Co, USA) for intermediate, Snellen chart for far and Landolt ring chart for near vision **Measure:** Visual Acuity **Time Frame:** 3 months **Description:** examined monocular and binocular after correcting distant VA refractive error then inserting defocus lenses 0.50-D focus steps from (+1.50 to -3.50 D) in the trial frame **Measure:** Defocus curve **Time Frame:** 3 months #### Secondary Outcomes **Description:** using the CSV-1000 contrast test. **Measure:** Contrast sensitivity **Time Frame:** 3 months **Description:** Questionnaire patient satisfaction protocol mediated by (PhysIOL Lige, Belgium). **Measure:** Visual Satisfaction Questionnaire **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * patient eyes had cataract with no other pathology, patients desire for spectacle independence after surgery and with realistic expectation. Exclusion Criteria: * Any ocular comorbidity that affect the end results of the surgery, history of ocular trauma, irregular corneal astigmatism, pupil abnormalities and capsular or zonular abnormalities that may affect postoperative centration as tilt of the lens (e.g. pseudo exfoliation syndrome and Marfan's syndrome). **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Alexandria **Country:** Egypt **Facility:** Alexandria Faculty of Medicine #### Overall Officials **Official 1:** **Affiliation:** Alexandria Faculty of Medicine **Name:** Ehab Mossallam, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Zein El-Dein AA, Elmassry A, El-Hennawi HM, Mossallam EF. Objective and subjective evaluation of trifocal diffractive intraocular Lens after cataract extraction with phacoemulsification: a prospective clinical study. BMC Ophthalmol. 2021 Apr 14;21(1):179. doi: 10.1186/s12886-021-01937-z. **PMID:** 33849466 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007905 - Term: Lens Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5638 - Name: Cataract - Relevance: HIGH - As Found: Cataract - ID: M14872 - Name: Refractive Errors - Relevance: HIGH - As Found: Refractive Errors - ID: M29066 - Name: Capsule Opacification - Relevance: HIGH - As Found: After Cataract - ID: M10917 - Name: Lens Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002386 - Term: Cataract - ID: D000012030 - Term: Refractive Errors - ID: D000058442 - Term: Capsule Opacification ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01707979 **Acronym:** NIR **Brief Title:** NIR- and Multifrequent Impedance Spectroscopy on the Skin in Type 1 Diabetes **Official Title:** NIR (Near Infrared)- Spectroscopy and Multifrequent Impedance Spectroscopy on the Skin to Detection of Sensory and Autonomic Neuropathy Among Patients With Type 1 Diabetes #### Organization Study ID Info **ID:** NIR #### Organization **Class:** OTHER **Full Name:** Steno Diabetes Center Copenhagen ### Status Module #### Completion Date **Date:** 2012-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-10-16 **Type:** ESTIMATED **Last Update Submit Date:** 2012-10-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-10 **Type:** ACTUAL #### Start Date **Date:** 2012-09 **Status Verified Date:** 2012-10 #### Study First Post Date **Date:** 2012-10-16 **Type:** ESTIMATED **Study First Submit Date:** 2012-09-25 **Study First Submit QC Date:** 2012-10-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Lise Tarnow #### Responsible Party **Investigator Affiliation:** Steno Diabetes Center Copenhagen **Investigator Full Name:** Lise Tarnow **Investigator Title:** Professor, Chief Physician **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of the study is to examine the suitability to detect diabetic neuropathy using NIR and impedance. **Detailed Description:** The aim of the study is to examine how suitable a hand-held measuring probe (DDD-probe) using NIR (near infrared light) as well as impedance (conductivity), is to detect early signs of diabetic neuropathy. The DDD-probe is put directly on the skin and is measuring by the use of light and impedance. ### Conditions Module **Conditions:** - Diabetic Neuropathy **Keywords:** - Near infrared light - Diabetic neuropathy - Sensory neuropathy - Autonomic neuropathy - Vagus - Sudomotor function - Monofilament - Impedance ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Male participants, type1 diabetic with diabetic neuropathy **Label:** Diabetic neuropathy #### Arm Group 2 **Description:** Male participants, type1 diabetic without diabetic neuropathy **Label:** Diabetes without neuropathy #### Arm Group 3 **Description:** Male participants, control group non diabetic **Label:** Non diabetic control ### Outcomes Module #### Primary Outcomes **Description:** Near infrared (NIR) is measured by spectroscopy on the skin using the DDD probe **Measure:** near infrared spectroscopy **Time Frame:** one time ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * men with type 1 diabetes (WHO criteria) * age 35-50 years * duration of diabetes \> 10 years Exclusion Criteria: * P-creatinine\> 120 micromol/l * other acute or chronic disease, or type of treatment that makes the patient unsuitable to participate, valuated by the investigator * non intact skin on the measuring spots * the patient is unable to understand the informed consent **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 35 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** MALE **Standard Ages:** - ADULT **Study Population:** Control group men without diabetes Type1 diabetic men without neuropathy complications Type 1 diabetic men with neuropathy complications ### Contacts Locations Module #### Locations **Location 1:** **City:** Gentofte **Country:** Denmark **Facility:** Steno Diabetes Center **Zip:** 2820 #### Overall Officials **Official 1:** **Affiliation:** Steno Diabetes Center Copenhagen **Name:** Lise Tarnow, Professor **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003920 - Term: Diabetes Mellitus - ID: D000004700 - Term: Endocrine System Diseases - ID: D000010523 - Term: Peripheral Nervous System Diseases - ID: D000009468 - Term: Neuromuscular Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000048909 - Term: Diabetes Complications ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M7117 - Name: Diabetes Mellitus, Type 1 - Relevance: LOW - As Found: Unknown - ID: M7124 - Name: Diabetic Neuropathies - Relevance: HIGH - As Found: Diabetic Neuropathy - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M13432 - Name: Peripheral Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M12411 - Name: Neuromuscular Diseases - Relevance: LOW - As Found: Unknown - ID: M26004 - Name: Diabetes Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003929 - Term: Diabetic Neuropathies ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03746379 **Brief Title:** Investigation of the Relationship Between Sensory Processing and Kinesychophobia in Fibromyalgia Patients **Official Title:** Investigation of the Relationship Between Sensory Processing and Kinesychophobia in #### Organization Study ID Info **ID:** 2018/359 #### Organization **Class:** OTHER **Full Name:** Hacettepe University ### Status Module #### Completion Date **Date:** 2019-02-18 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2018-11-19 **Type:** ACTUAL **Last Update Submit Date:** 2018-11-16 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-01-17 **Type:** ESTIMATED #### Start Date **Date:** 2018-12-16 **Type:** ESTIMATED **Status Verified Date:** 2018-11 #### Study First Post Date **Date:** 2018-11-19 **Type:** ACTUAL **Study First Submit Date:** 2018-11-15 **Study First Submit QC Date:** 2018-11-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hacettepe University #### Responsible Party **Investigator Affiliation:** Trakya University **Investigator Full Name:** Özgü İNAL **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Fibromyalgia; is a chronic and rheumatic condition characterized by diffuse pain. In patients with fibromyalgia syndrome, there is an increase in psychiatric symptoms, especially depression, anxiety, and somatoform disorders. Kinesophobia is defined as anxiety against pain and pain caused by painful injury and re-injury. The aim of this study was to investigate the relationship between kinesophobia and sensory processing in patients with fibromyalgia. **Detailed Description:** Fibromyalgia; is a chronic and rheumatic condition characterized by diffuse pain. In patients with fibromyalgia syndrome, there is an increase in psychiatric symptoms, especially depression, anxiety, and somatoform disorders. Kinesophobia is defined as anxiety against pain and pain caused by painful injury and re-injury. The aim of this study was to investigate the relationship between kinesophobia and sensory processing in patients with fibromyalgia. ### Conditions Module **Conditions:** - Fybromyalgia **Keywords:** - kinezyhophobia - sensory processing - fybromyalgia ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 82 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Sensory processing disorder refers to the difficulty of processing the information coming from the sensory organs, and the inefficiency of the normal sensory processing process.For the evaluation of sensory processing; Sensory Adolescent / Adult Sensory Profile questionnaire will be used. **Measure:** Sensory processing assessed with the Sensory Adolescent / Adult Sensory Profile Questionnaire **Time Frame:** at the end of the third month **Description:** Kinezyophobia is defined as anxiety against pain and pain caused by painful injury and re-injury. For the evaluation of kinesiophobia; Tampa Kineshiophobia Scale will be used. **Measure:** Knesychophobia assessed with the Tampa Kineshiophobia Scale **Time Frame:** at the end of the third month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 18-65 years old * Diagnosed by fibromyalgia * No other known physical, neurological and psychological illness * Literate * Volunteers to participate in the study Exclusion Criteria: * Not compliant with inclusion criteria **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with fibromyalgia ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M8486 - Name: Fibromyalgia - Relevance: LOW - As Found: Unknown - ID: M12161 - Name: Myofascial Pain Syndromes - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04066179 **Brief Title:** Efficacy of Monotherapy vs Combination Therapy of Corticosteroids With GCSF in Severe Alcoholic Hepatitis Patients. **Official Title:** Efficacy of Monotherapy vs Combination Therapy of Corticosteroids With GCSF in Severe Alcoholic Hepatitis Patients -A Randomized Controlled Trial. #### Organization Study ID Info **ID:** ILBS-AH-03 #### Organization **Class:** OTHER **Full Name:** Institute of Liver and Biliary Sciences, India ### Status Module #### Completion Date **Date:** 2021-02-27 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2019-09-09 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-05 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-02-27 **Type:** ESTIMATED #### Start Date **Date:** 2019-09-07 **Type:** ESTIMATED **Status Verified Date:** 2019-08 #### Study First Post Date **Date:** 2019-08-26 **Type:** ACTUAL **Study First Submit Date:** 2019-08-14 **Study First Submit QC Date:** 2019-08-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Institute of Liver and Biliary Sciences, India #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The patients of Severe Alcoholic Hepatitis (SAH) will be included in study based on inclusion and exclusion criteria. The patients will be then randomized in 3 groups for therapy. They will receive either steroid or Granulocyte-Colony Stimulating Factor (GCSF) or both. They will be followed for atleast 90 days for improvements in symptoms and various predefined parameters. Primary outcome will be improvement in survival at 90 Days. Patients will be monitored at every follow up for disease progression and complications of therapy. The study results will be analyzed for differences in survival rate and complications in different groups to propose new therapeutic guideline in SAH patients. ### Conditions Module **Conditions:** - Alcoholic Hepatitis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 126 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Prednisolone 40 mg/day for initial 7 days G-CSF300 microgram daily for 7 days **Intervention Names:** - Drug: Gcsf - Drug: Prednisolone **Label:** Prednisolone+G-CSF **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Prednisolone 40 mg/day for 7 days **Intervention Names:** - Drug: Prednisolone **Label:** Prednisolone **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Granulocytes-Colony Stimulating Factor 300 mcg for 7 days followed by 300 mcg every 3 days **Intervention Names:** - Drug: Gcsf **Label:** Granulocytes-Colony Stimulating Factor **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Granulocytes-Colony Stimulating Factor - Prednisolone+G-CSF **Description:** Granulocytes-Colony Stimulating Factor 300 mcg for 7 days followed by 300 mcg every 3 days **Name:** Gcsf **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Prednisolone - Prednisolone+G-CSF **Description:** Prednisolone 40 mg for initial 7 days **Name:** Prednisolone **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** increase in Survival at 90 days in all the groups. **Time Frame:** 90 days #### Secondary Outcomes **Description:** CTP- Child-Turcotte-Pugh score ranges from 5 to 15, lowest is best and highest is worst. **Measure:** Improvement in CTP (Child-Pugh Score) in all the groups. **Time Frame:** Day 28 **Description:** CTP- Child-Turcotte-Pugh score ranges from 5 to 15, lowest is best and highest is worst. **Measure:** Improvement in CTP (Child-Pugh Score) in all the groups. **Time Frame:** Day 180 **Description:** A disease severity scoring system for adults with liver disease, designed to improve the organ allocation in transplantation based on the severity of liver disease rather than the length of time on the waiting list. A MELD score is a number that ranges from 6 to 40, based on lab tests. **Measure:** Improvement in MELD (Model for End Stage Liver Disease) in all the groups. **Time Frame:** Day 28 **Description:** A disease severity scoring system for adults with liver disease, designed to improve the organ allocation in transplantation based on the severity of liver disease rather than the length of time on the waiting list. A MELD score is a number that ranges from 6 to 40, based on lab tests. **Measure:** Improvement in MELD (Model for End Stage Liver Disease) in all the groups. **Time Frame:** Day 180 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Severe alcoholic hepatitis patients \[Maddrey's score \> 32\] aged between 18 to 65 years. Exclusion Criteria: * Presence of active infections * Acute Gastrointestinal bleed * Hepatorenal syndrome * Patient unwilling * Discriminant Function \>90 * Autoimmune hepatitis * Hepatitis B, Hepatitis C, Human immunodeficiency Virus cases * Pregnancy * Hemophagocytic lymphohistiocytosis (HLH) * Hb\<8 and baseline White Blood Cell\>25000 **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Dr Ajay Mishra, MD **Phone:** 01146300000 **Role:** CONTACT #### Locations **Location 1:** **City:** New Delhi **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dr Ajay Mishra, MD - **Phone:** 01146300000 - **Role:** CONTACT **Country:** India **Facility:** Institute of Liver and Biliary Sciences **State:** Delhi **Status:** RECRUITING **Zip:** 110070 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000006525 - Term: Hepatitis, Viral, Human - ID: D000014777 - Term: Virus Diseases - ID: D000007239 - Term: Infections - ID: D000004769 - Term: Enterovirus Infections - ID: D000010850 - Term: Picornaviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008108 - Term: Liver Diseases, Alcoholic - ID: D000020751 - Term: Alcohol-Induced Disorders - ID: D000019973 - Term: Alcohol-Related Disorders - ID: D000019966 - Term: Substance-Related Disorders - ID: D000064419 - Term: Chemically-Induced Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC25 - Name: Substance Related Disorders - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M9605 - Name: Hepatitis, Alcoholic - Relevance: HIGH - As Found: Alcoholic Hepatitis - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M9610 - Name: Hepatitis, Viral, Human - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M7930 - Name: Enterovirus Infections - Relevance: LOW - As Found: Unknown - ID: M13745 - Name: Picornaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11108 - Name: Liver Diseases, Alcoholic - Relevance: LOW - As Found: Unknown - ID: M22508 - Name: Alcohol-Induced Disorders - Relevance: LOW - As Found: Unknown - ID: M21842 - Name: Alcohol-Related Disorders - Relevance: LOW - As Found: Unknown - ID: M21837 - Name: Substance-Related Disorders - Relevance: LOW - As Found: Unknown - ID: M30302 - Name: Chemically-Induced Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006506 - Term: Hepatitis A - ID: D000006505 - Term: Hepatitis - ID: D000006519 - Term: Hepatitis, Alcoholic ### Intervention Browse Module - Ancestors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018931 - Term: Antineoplastic Agents, Hormonal - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnEm - Name: Antiemetics - Abbrev: NeuroAg - Name: Neuroprotective Agents - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M14120 - Name: Prednisolone - Relevance: HIGH - As Found: Vein - ID: M1945 - Name: Lenograstim - Relevance: LOW - As Found: Unknown - ID: M11749 - Name: Methylprednisolone - Relevance: LOW - As Found: Unknown - ID: M1833 - Name: Methylprednisolone Acetate - Relevance: LOW - As Found: Unknown - ID: M11750 - Name: Methylprednisolone Hemisuccinate - Relevance: LOW - As Found: Unknown - ID: M229449 - Name: Prednisolone acetate - Relevance: LOW - As Found: Unknown - ID: M211887 - Name: Prednisolone hemisuccinate - Relevance: LOW - As Found: Unknown - ID: M248881 - Name: Prednisolone phosphate - Relevance: LOW - As Found: Unknown - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000011239 - Term: Prednisolone ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02638779 **Acronym:** REALISM **Brief Title:** REAnimation Low Immune Status Markers **Official Title:** REAnimation Low Immune Status Markers #### Organization Study ID Info **ID:** 69HCL15_0379 #### Organization **Class:** OTHER **Full Name:** Hospices Civils de Lyon #### Secondary ID Infos **Domain:** ID-RCB **ID:** 2015-A01293-46 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2018-06-27 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-09-17 **Type:** ACTUAL **Last Update Submit Date:** 2018-09-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-06-27 **Type:** ACTUAL #### Start Date **Date:** 2015-12-11 **Type:** ACTUAL **Status Verified Date:** 2018-09 #### Study First Post Date **Date:** 2015-12-23 **Type:** ESTIMATED **Study First Submit Date:** 2015-12-18 **Study First Submit QC Date:** 2015-12-18 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Bioaster **Class:** INDUSTRY **Name:** BioMérieux **Class:** INDUSTRY **Name:** Sanofi #### Lead Sponsor **Class:** OTHER **Name:** Hospices Civils de Lyon #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The fact that sepsis disrupts immune system homeostasis by inducing an initial cytokine storm, that participates to occurrence of organ failures and early death, followed by a compensatory anti-inflammatory response leading to immunosuppression, is now well established. This immunomodulating response results in a higher risk of secondary infections and is associated to 2/3 of deaths related to septic shocks. Follow up of patients' immune status with time is crucial to guide therapy management. Objective of REALISM project is to demonstrate existence of this immunosuppression phase, by providing strong epidemiologic data for septic shock patients, but also by extension to other situations of inflammatory aggressions like severe severe trauma or burns, or major surgery. This project will provide tools to predict occurrence of secondary infections and guide patient management by comparing innovating immunomonitoring tools to reference tests non already adapted to a routine patient management. Targeted populations are adult patients hospitalized for septic shock, severe trauma (including severe burn) or major surgery and healthy volunteers, whom blood samples will serve to validate reference intervals of the two reference tests. ### Conditions Module **Conditions:** - Septic Shock - Severe Trauma - Severe Burn - Major Surgery **Keywords:** - Septic shock - severe trauma - severe burn - major surgery - immunosuppression - Healthcare-Associated Infections ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 552 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Blood sampling will be performed in all patients and healthy volunteers **Intervention Names:** - Biological: Blood sampling **Label:** Blood sampling **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Blood sampling **Description:** Specific Blood sampling will be performed in patients and healthy volunteers **Name:** Blood sampling **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** The immunosuppression status will be determined from two immunological reference tests: (1) lymphocyte proliferation in response to ex vivo T cell stimulation (adaptive immunity) (Poujol et al., 2014) and (2) the production of tumor necrosis factor (TNF) by monocytes in response to ex vivo stimulation by lipopolysaccharide (LPS) (innate immunity) (Duffy et al., 2014). The values measured will be defined as normal or abnormal, depending on whether they are within reference intervals (RI) derived from an independent set of healthy volunteers. For this purpose, the definition of immunosuppression will be: an abnormal result in at least one of the two "reference" tests (outside the reference intervals defining normal values), and on at least two consecutive samples. The same reference test must be abnormal in two successive samples examined for the patient to be considered immunosuppressed. **Measure:** Percentage of patients meeting the definition of of injury-induced-immunosuppression **Time Frame:** Up to 2 months after injury #### Secondary Outcomes **Description:** Intensity of the innate immune deficiency will be measured using the production of TNF by monocytes in response to ex vivo stimulation by LPS (Duffy et al., 2014). Intensity of the adaptive immune deficiency will be measured using the lymphocyte proliferation in response to ex vivo T cell stimulation (Poujol et al., 2014). The values measured will be defined as normal or abnormal, depending on whether they are within reference intervals derived from an independent set of healthy volunteers. We will describe for all groups of patients: * The proportion of patients with a deficiency of the innate immunity, defined by an abnormal TNF secretion test result after LPS stimulation, for at least two consecutive samples. * The proportion of patients with a deficiency of the adaptive immunity, defined by an abnormal lymphocyte proliferation, for at least two consecutive samples. * The proportion of patients with at least one abnormal test on Days 1, 3-4, 5-7, 13/18, 26/36 and 52/68 **Measure:** Proportion of patients with a deficiency of the innate or adaptive immunity **Time Frame:** Up to 2 months after injury **Description:** Reference tests being non-standardized and cumbersome to implement, and time to results being incompatible with clinical practice, the use of simpler and quicker tests, based on the use of new biomarkers, would allow the individualization of patient management based on the patient's immune status. One of the secondary objectives is to evaluate the performance of new biomarkers compared to the two reference tests to diagnose immunosuppression. Different types of markers and tests will be evaluated: Viral reactivation markers, host-response markers, immune functional assays, immunophenotyping. **Measure:** Comparison of performance of the reference tests and new biomarkers for the diagnosis of immunosuppression **Time Frame:** Up to one week after injury **Description:** To evaluate the association between the immunosuppression status as defined in primary objective and the occurrence of secondary infections related to healthcare, the association of the immunosuppression status upon the occurrence of secondary infection will be examined first, and secondly any possible association between the levels of each of the reference tests and the occurrence of secondary infections will be characterized. In this analysis, a secondary infection related to healthcare will be defined as an infection occurring after inclusion in the study, between inclusion and day 28. **Measure:** Correlation between the immunosuppression status and the incidence of healthcare-associated infections **Time Frame:** Up to 28 days after injury **Description:** We will examine the association between immunosuppression (as defined in the primary objective) and in-hospital mortality. Association will be evaluated par measuring occurrence of mortality at days 14, 28, 60 and 90, in the different groups. **Measure:** Correlation between immunosuppression and mortality **Time Frame:** Up to 90 days after injury **Description:** The possibility of taking a sample before surgical stress should allow measurements of the impact of the procedure on the host response, and especially on any subsequent onset of immunosuppression. Oncological pathologies and treatments implemented prior to surgery may also be associated with immunosuppression, and for this reason patients hospitalized for cancer surgery will be compared to those hospitalized for vascular surgery. Impact of surgery on immunosuppression will be measured by comparing immune status as defined by the reference tests, in the population of surgical patients before and after surgery. **Measure:** Comparison of immune status before and after surgery in the population of surgical patients **Time Frame:** Up to 2 months after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion criteria for patients * Patient or next of kin having been informed of the conditions of the study and having signed the informed consent form * Patient hospitalized for : * Septic shock * Severe trauma (including severe burn) * Major surgery Inclusion criteria for healthy volunteers * Normal clinical examination * Signed informed consent form * Person with social security insurance Exclusion criteria for patients * Patient with severe neutropenia (neutrophil count \<0.5 g/l) * Patients receiving immunosuppressive therapy * Patients receiving corticosteroids (IV or Per os) * Use of therapeutic antibodies * Hematological disease under treatment, or treated within 5 years before inclusion * End of chemotherapy within the 6 months prior to inclusion * Patient with innate or acquired immune deficiency (for example severe combined immunodeficiency, HIV or AIDS, any stage) * Patients for whom a care limitation was pronounced at time of enrolment * Anticipated length of stay before discharge from the ICU is estimated at less than 48 hours * Participation in an intervention study * Extra-corporeal circulation in the month preceding inclusion in case of cardiac surgery * Pregnant or breastfeeding women * Patient with no social security insurance, with restricted liberty or under legal protection Exclusion criteria for healthy volunteers * Person with an infectious syndrome during the last 90 days * Extreme physical stress within the last week * Person having received within the last 90 days, a treatment based on * Antivirals * Antibiotics * Antiparasitics * Antifungics * Person having received within the last 15 days, a treatment based on non-steroidal anti-inflammatory drugs (NSAIDs) * Person having received within the last 24 months, a treatment based on * Immunosuppressive therapy * Corticosteroids (IV or Per os) * Therapeutic antibodies * Chemotherapy * History of : * innate or acquired immune deficiency * Hematological disease * Solid tumor * Severe chronic disease * Surgery or hospitalization within the last 2 years * Pregnancy within the last year * Participation to a phase I clinical assay during the last year * Pregnant or breastfeeding women * Person with restricted liberty or under legal protection **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** LYON cedex 03 **Country:** France **Facility:** Service d'Anesthésie Réanimation - Hôpital Edouard Herriot **Zip:** 69437 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Bodinier M, Peronnet E, Brengel-Pesce K, Conti F, Rimmele T, Textoris J, Vedrine C, Quemeneur L, Griffiths AD, Tan LK, Venet F, Maucort-Boulch D, Monneret G; REALISM study group. Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients. Front Immunol. 2021 Nov 29;12:795052. doi: 10.3389/fimmu.2021.795052. eCollection 2021. **PMID:** 34912347 **Citation:** Mallet F, Diouf L, Meunier B, Perret M, Reynier F, Leissner P, Quemeneur L, Griffiths AD, Moucadel V, Pachot A, Venet F, Monneret G, Lepape A, Rimmele T, Tan LK, Brengel-Pesce K, Textoris J. Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study. Front Immunol. 2021 Nov 2;12:698808. doi: 10.3389/fimmu.2021.698808. eCollection 2021. **PMID:** 34795661 **Citation:** Venet F, Textoris J, Blein S, Rol ML, Bodinier M, Canard B, Cortez P, Meunier B, Tan LK, Tipple C, Quemeneur L, Reynier F, Leissner P, Vedrine C, Bouffard Y, Delwarde B, Martin O, Girardot T, Truc C, Griffiths AD, Moucadel V, Pachot A, Monneret G, Rimmele T; REALISM study group. Immune Profiling Demonstrates a Common Immune Signature of Delayed Acquired Immunodeficiency in Patients With Various Etiologies of Severe Injury. Crit Care Med. 2022 Apr 1;50(4):565-575. doi: 10.1097/CCM.0000000000005270. Erratum In: Crit Care Med. 2022 Jun 1;50(6):e618. **PMID:** 34534131 **Citation:** Rol ML, Venet F, Rimmele T, Moucadel V, Cortez P, Quemeneur L, Gardiner D, Griffiths A, Pachot A, Textoris J, Monneret G; REALISM study group. The REAnimation Low Immune Status Markers (REALISM) project: a protocol for broad characterisation and follow-up of injury-induced immunosuppression in intensive care unit (ICU) critically ill patients. BMJ Open. 2017 Jun 21;7(6):e015734. doi: 10.1136/bmjopen-2016-015734. **PMID:** 28637738 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012769 - Term: Shock - ID: D000010335 - Term: Pathologic Processes - ID: D000018805 - Term: Sepsis - ID: D000007239 - Term: Infections - ID: D000018746 - Term: Systemic Inflammatory Response Syndrome - ID: D000007249 - Term: Inflammation ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M15580 - Name: Shock, Septic - Relevance: HIGH - As Found: Septic Shock - ID: M15577 - Name: Shock - Relevance: LOW - As Found: Unknown - ID: M5326 - Name: Burns - Relevance: LOW - As Found: Unknown - ID: M6642 - Name: Cross Infection - Relevance: LOW - As Found: Unknown - ID: M20864 - Name: Sepsis - Relevance: LOW - As Found: Unknown - ID: M16869 - Name: Toxemia - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M20818 - Name: Systemic Inflammatory Response Syndrome - Relevance: LOW - As Found: Unknown - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012772 - Term: Shock, Septic ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05134779 **Acronym:** DIGNITY **Brief Title:** De-convoluting Interactions Between Genes, the Cancer Environment, and the Immune System to Develop Therapies That Work for You **Official Title:** De-convoluting Interactions Between Genes, the Cancer Environment, and the Immune System to Develop Therapies That Work for You #### Organization Study ID Info **ID:** 21-06023682 #### Organization **Class:** OTHER **Full Name:** Weill Medical College of Cornell University ### Status Module #### Completion Date **Date:** 2028-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-27 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2027-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2022-01-12 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2021-11-26 **Type:** ACTUAL **Study First Submit Date:** 2021-10-04 **Study First Submit QC Date:** 2021-11-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Weill Medical College of Cornell University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a live biobank study for breast cancer (BC) patients where samples will be collected at inflection points in the course of the disease. **Detailed Description:** To test this hypothesis the investigators will focus on studying BC patients using an innovative approach, the DIGNITY Study (De-convoluting interactions between genes, the cancer environment, and the immune system to develop therapies that work for you) designed to building a live tissue biobank of Patient Derived Tumor Organoids (PDOs) derived from tumor at surgery, preceded or not by neoadjuvant therapy (NAT), and at recurrence/metastasis. BC patients enrolled in this study are consented to enable investigators to generate a biobank of tumor tissue (obtained from surgically removed excess that would otherwise be disposed off ) and matched blood cells ( obtained from an already existing line or a venipuncture ordered per standard of care testing) at key timepoints in their treatment course. ### Conditions Module **Conditions:** - Breast Cancer ### Design Module #### Bio Spec **Description:** Tissue collection through the DIGNITY trial will allow the investigators to study the individual tumor and its microenvironment from a biopsy specimen at sequential inflection points and to perform functional genomics experiments using the PDOs technology to determine if the cancer cells can be reprogrammed using radiotherapy and other interventions. Paired blood samples from the patients at each time point will be collected to study circulating cytokines/chemokines, tumor-specific T cells, and innate immune cell response to the PDO. **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 400 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with breast cancer (BC), any stage will be considered for this study. **Intervention Names:** - Procedure: Live Biobank **Label:** Cohort 1 ### Interventions #### Intervention 1 **Arm Group Labels:** - Cohort 1 **Description:** Tumor tissue will be collected from consented patients at sequential inflection points in the disease course: at the time of initial diagnosis, at the time of surgery and during recurrence or metastasis. In addition to this, 40ml of research bloods will also be collected at these key inflection points. **Name:** Live Biobank **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Tumor tissue will be obtained at key inflection points from breast cancer patients (BC): at initial diagnosis, at surgery and at metastasis or recurrence. Patient Derived Organoids (PDOs) will be prepared from tumors that are obtained from the BC patients. **Measure:** establish a live biobank for breast cancer patients **Time Frame:** 60 months #### Secondary Outcomes **Description:** comprehensively characterize the tumor from the biospecimen to determine the mutations, expression of immune related genes, and the quality and the spatial distribution of the immune infiltrate **Measure:** assess immune relevant genes from tumor biopsies **Time Frame:** 60 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All patients will historically proven BC are eligible to be on the study Exclusion Criteria: * Carriers of other cancers other than breast. **Gender Based:** True **Maximum Age:** 90 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** breast cancer patients (BC), any stage irrespective of hormonal status will be eligible for this study. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Sharanya Chandrasekhar, M.S. **Phone:** 646-962-3110 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Pragya Yadav, Ph.D. **Phone:** 646-962-2196 **Role:** CONTACT #### Locations **Location 1:** **City:** New York **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Sharanya Chandrasekhar, M.S. - **Phone:** 646-962-3110 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Pragya Yadav, Ph.D. - **Phone:** 6469622196 - **Role:** CONTACT ***Contact 3:*** - **Name:** Hani Ashamalla, M.D. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Brooklyn Methodist Hospital - NewYork Presbyterian **State:** New York **Status:** RECRUITING **Zip:** 11215 **Location 2:** **City:** New York **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Sarah Stankiewicz, B.S. - **Phone:** 718-661-7246 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Sharanya Chandrasekhar, M.S. - **Phone:** 646-962-2196 - **Role:** CONTACT ***Contact 3:*** - **Name:** Akkamma Ravi, M.D. - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Silvia Formenti, M.D. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** New York Presbyterian Hospital - Queens **State:** New York **Status:** RECRUITING **Zip:** 11355 #### Overall Officials **Official 1:** **Affiliation:** Weill Medical College of Cornell University **Name:** Silvia Formenti, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT00279279 **Brief Title:** PREPARE - Primary Prevention Parameters Evaluation **Official Title:** PREPARE - Primary Prevention Parameters Evaluation #### Organization Study ID Info **ID:** 223 #### Organization **Class:** INDUSTRY **Full Name:** Medtronic Cardiac Rhythm and Heart Failure ### Status Module #### Completion Date **Date:** 2006-05 #### Expanded Access Info #### Last Update Post Date **Date:** 2006-10-26 **Type:** ESTIMATED **Last Update Submit Date:** 2006-10-25 **Overall Status:** COMPLETED #### Start Date **Date:** 2003-10 **Status Verified Date:** 2006-10 #### Study First Post Date **Date:** 2006-01-19 **Type:** ESTIMATED **Study First Submit Date:** 2006-01-17 **Study First Submit QC Date:** 2006-01-17 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Medtronic #### Lead Sponsor **Class:** INDUSTRY **Name:** Medtronic Cardiac Rhythm and Heart Failure ### Description Module **Brief Summary:** The purpose of this study is to test specific device programming in patients without a previous history of a life-threatening, abnormally fast heartbeat who are implanted with a Medtronic ICD (Implantable Cardioconverter Defibrillator) or ICD with CRT (Cardiac Resynchronozation Therapy) device. The information learned from this study could be used to guide physicians in future ICD or CRT device programming. ### Conditions Module **Conditions:** - Tachycardia, Ventricular - Implantable Cardioverter Defibrillator (ICD) - Fibrillation, Ventricular - Syncope **Keywords:** - Implantable cardioverter defibrillator (ICD) - Sudden Cardiac Death - Primary Prevention ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 700 **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Implanted Device **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** Demonstrate that patients programmed using a prescribed set of parameters have a lower rate of cardiac syncope, symptoms of fast heart rate, VT/VF events and cardioversion or defibrillation shocks compared to patients programmed per physician discretion #### Secondary Outcomes **Measure:** Evaluate the percentage of inappropriate VT/VF detections **Measure:** characterize the true incidence of VT/VF detections **Measure:** therapy efficacy **Measure:** time to first inappropriate VT/VF detection **Measure:** incidence of untreated but monitored VT **Measure:** programming changes **Measure:** deaths and cardiovascular adverse event ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Patient is a candidate for a non-replacement Medtronic ICD device from the Marquis family or has had a non-replacement Medtronic Marquis based ICD system implanted within the previous 6 months and has not had any appropriately treated spontaneous VT/VF episodes during that time. Exclusion Criteria: Patient has history of spontaneous sustained symptomatic ventricular arrhythmias. If patient has had an electrophysiology test in the past, and has sustained inducible VT \<180 bpm. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **State:** Alabama **Location 2:** **City:** Mesa **Country:** United States **State:** Arizona **Location 3:** **City:** Phoenix **Country:** United States **State:** Arizona **Location 4:** **City:** San Diego **Country:** United States **State:** California **Location 5:** **City:** San Pablo **Country:** United States **State:** California **Location 6:** **City:** Newark **Country:** United States **State:** Delaware **Location 7:** **City:** Ft. Lauderdale **Country:** United States **State:** Florida **Location 8:** **City:** Jacksonville **Country:** United States **State:** Florida **Location 9:** **City:** Merrit Island **Country:** United States **State:** Florida **Location 10:** **City:** Columbus **Country:** United States **State:** Georgia **Location 11:** **City:** Maywood **Country:** United States **State:** Illinois **Location 12:** **City:** Rockford **Country:** United States **State:** Illinois **Location 13:** **City:** Topeka **Country:** United States **State:** Kansas **Location 14:** **City:** Portland **Country:** United States **State:** Maine **Location 15:** **City:** Silver Spring **Country:** United States **State:** Maryland **Location 16:** **City:** Takoma Park **Country:** United States **State:** Maryland **Location 17:** **City:** Boston **Country:** United States **State:** Massachusetts **Location 18:** **City:** Royal Oak **Country:** United States **State:** Michigan **Location 19:** **City:** Minneapolis **Country:** United States **State:** Minnesota **Location 20:** **City:** Paterson **Country:** United States **State:** New Jersey **Location 21:** **City:** Buffalo **Country:** United States **State:** New York **Location 22:** **City:** New York **Country:** United States **State:** New York **Location 23:** **City:** Columbus **Country:** United States **State:** Ohio **Location 24:** **City:** Elyria **Country:** United States **State:** Ohio **Location 25:** **City:** Bethlehem **Country:** United States **State:** Pennsylvania **Location 26:** **City:** Lancaster **Country:** United States **State:** Pennsylvania **Location 27:** **City:** Columbia **Country:** United States **State:** South Carolina **Location 28:** **City:** Nashville **Country:** United States **State:** Tennessee **Location 29:** **City:** Amarillo **Country:** United States **State:** Texas **Location 30:** **City:** Kirkland **Country:** United States **State:** Washington **Location 31:** **City:** Morgantown **Country:** United States **State:** West Virginia **Location 32:** **City:** San Juan **Country:** Puerto Rico #### Overall Officials **Official 1:** **Affiliation:** The Cleveland Clinic **Name:** Bruce Wilkoff, M.D **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** van Gelder IC, Phan HM, Wilkoff BL, Brown ML, Rogers T, Peterson BJ, Birgersdotter-Green UM. Prognostic significance of atrial arrhythmias in a primary prevention ICD population. Pacing Clin Electrophysiol. 2011 Sep;34(9):1070-9. doi: 10.1111/j.1540-8159.2011.03124.x. Epub 2011 May 23. **PMID:** 21605131 **Citation:** Wilkoff BL, Williamson BD, Stern RS, Moore SL, Lu F, Lee SW, Birgersdotter-Green UM, Wathen MS, Van Gelder IC, Heubner BM, Brown ML, Holloman KK; PREPARE Study Investigators. Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol. 2008 Aug 12;52(7):541-50. doi: 10.1016/j.jacc.2008.05.011. **PMID:** 18687248 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000075224 - Term: Cardiac Conduction System Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000014474 - Term: Unconsciousness - ID: D000003244 - Term: Consciousness Disorders - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M6845 - Name: Death - Relevance: LOW - As Found: Unknown - ID: M16384 - Name: Tachycardia - Relevance: HIGH - As Found: Tachycardia - ID: M19488 - Name: Tachycardia, Ventricular - Relevance: HIGH - As Found: Tachycardia, Ventricular - ID: M16353 - Name: Syncope - Relevance: HIGH - As Found: Syncope - ID: M19118 - Name: Death, Sudden, Cardiac - Relevance: LOW - As Found: Unknown - ID: M17439 - Name: Ventricular Fibrillation - Relevance: HIGH - As Found: Fibrillation, Ventricular - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M1472 - Name: Cardiac Conduction System Disease - Relevance: LOW - As Found: Unknown - ID: M17224 - Name: Unconsciousness - Relevance: LOW - As Found: Unknown - ID: M6468 - Name: Consciousness Disorders - Relevance: LOW - As Found: Unknown - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T4437 - Name: Paroxysmal Ventricular Fibrillation - Relevance: HIGH - As Found: Fibrillation, Ventricular ### Condition Browse Module - Meshes - ID: D000013575 - Term: Syncope - ID: D000013610 - Term: Tachycardia - ID: D000017180 - Term: Tachycardia, Ventricular - ID: D000014693 - Term: Ventricular Fibrillation ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04041479 **Acronym:** BioTMS **Brief Title:** Biomarker-guided rTMS for Treatment Resistant Depression **Official Title:** Efficacy of Biomarker-guided rTMS for Treatment Resistant Depression #### Organization Study ID Info **ID:** 21-08023811; prev 1810019638 #### Organization **Class:** OTHER **Full Name:** Weill Medical College of Cornell University #### Secondary ID Infos **ID:** R01MH118388 **Link:** https://reporter.nih.gov/quickSearch/R01MH118388 **Type:** NIH ### Status Module #### Completion Date **Date:** 2026-08 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-23 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-22 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-04 **Type:** ESTIMATED #### Start Date **Date:** 2021-09-17 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2019-08-01 **Type:** ACTUAL **Study First Submit Date:** 2019-07-31 **Study First Submit QC Date:** 2019-07-31 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Mental Health (NIMH) **Class:** OTHER **Name:** Stanford University #### Lead Sponsor **Class:** OTHER **Name:** Weill Medical College of Cornell University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Repetitive transcranial magnetic stimulation (rTMS) is a treatment for depression. The investigators are continuing to learn how to optimize outcomes from rTMS treatment. The purpose of this research project is to use brain network connectivity patterns as measured by resting state functional magnetic resonance imaging (fMRI) to confirm a way to optimize the use of rTMS to treat depression. In addition, the study aims to gain a better understanding of how rTMS influences brain networks. **Detailed Description:** Major depressive disorder (MDD) is a leading cause of global disability, and approximately 30% of MDD patients are resistant to antidepressant pharmacotherapy. Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an FDA-cleared intervention with proven efficacy in treatment-resistant depression, but only 30-40% of these patients achieve remission after a single course. Other studies have shown that rTMS targeting the dorsomedial prefrontal cortex (DMPFC) is comparably effective, but biomarkers for informing target site selection do not exist. Diagnostic heterogeneity has been an obstacle to biomarker discovery efforts. Recently, we developed and validated an approach to diagnose four novel MDD subtypes or "biotypes' defined by resting state functional connectivity (RSFC) patterns and predicting differing antidepressant responses at the individual level to rTMS. This pivotal trial will test a novel, biotype-guided treatment selection strategy motivated by the hypothesis that an individual patient's likelihood of responding to left DLFPC vs.DMPFC rTMS is determined in part by individual differences in 1) the degree to which their symptoms are driven by dysfunction in specific cerebral network targets comprising Valence Systems; and 2) the degree to which dysfunction in those targets can be modulated by stimulating the left DLPFC or DMPFC. Subjects (N=348; 174 from this site) will be randomized to receive a) biotype-guided rTMS targeting the DMPFC or left DLPFC; b) to a disconfirmation arm receiving rTMS targeting the opposite site; and c) to a third arm receiving FDA-cleared, standard-of-care rTMS targeting the left DLFPC, regardless of biotype. The dosage and method of delivery of rTMS for all arms are as follows: intermittent theta burst stimulation (iTBS) will be delivered at 120% of the resting motor threshold. It will be administered in triplet 50 Hz bursts, repeated at 5 Hz with a duty cycle of 2 s on and 8 s off, for a total of 600 pulses per session and a total duration of 3 min 9 s. All patients will be assessed before and after treatment on a battery of fMRI, behavioral, and clinical assessments. The primary goal is to confirm the efficacy of a novel RSFC biomarker-guided approach to differential treatment selection in treatment resistant depression. ### Conditions Module **Conditions:** - Treatment Resistant Depression - Major Depressive Disorder ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Human subjects in the proposed protocol will be randomized to receive a) biotype-guided rTMS to the left DLPFC or to the DMPFC; b) rTMS targeted to the opposite site; and c) standard-of-care left DLPFC rTMS. The dosage and method of delivery of rTMS are as follows: intermittent theta burst stimulation (iTBS) will be delivered at 120% of the resting motor threshold. It will be administered in triplet 50 Hz bursts, repeated at 5 Hz with a duty cycle of 2 s on and 8 s off, for a total of 600 pulses per session and a total duration of 3 min 9 s. Participants will receive screening and diagnostic interviews, phenotypic assessment (including demographic information, cognitive assessments, and behavioral functioning), structured clinical interviews, and magnetic resonance imaging (including structural and functional MRI). ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 348 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** FDA-cleared, standard-of-care iTBS repetitive Transcranial Magnetic Stimulation targeting the left dorsolateral prefrontal cortex (DLPFC), regardless of the depression subtype (biotype) determined by a magnetic resonance imaging (MRI) scan. **Intervention Names:** - Device: Repetitive Transcranial Magnetic Stimulation **Label:** Standard of Care **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** iTBS rTMS targeting the area of the brain (DLPFC or dorsomedial prefrontal cortex DMPFC)) that we hypothesize will be most effective for that subject's biotype (confirmation arm). **Intervention Names:** - Device: Repetitive Transcranial Magnetic Stimulation **Label:** Targeted Side Arm **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** iTBS rTMS targeting the opposite site (DLPFC or DMPFC) than the one we hypothesize will be most effective for that subject's biotype (disconfirmation arm). **Intervention Names:** - Device: Repetitive Transcranial Magnetic Stimulation **Label:** Opposite Side Arm **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Opposite Side Arm - Targeted Side Arm **Description:** iTBS rTMS targeting the DMPFC or left DLPFC **Name:** Repetitive Transcranial Magnetic Stimulation **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Standard of Care **Description:** iTBS rTMS targeting the left DLPFC **Name:** Repetitive Transcranial Magnetic Stimulation **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The Hamilton Depression Rating Scale (HAMD17) is a 17 item clinician-rated measure of depression severity. Scores of 0-7 = Normal, 8-13 = Mild Depression, 14-18 = Moderate Depression, 19-22 = Severe Depression, ≥ 23 = Very Severe Depression **Measure:** Change in depression, as measured by the Hamilton Depression Rating Scale (HAMD17) **Time Frame:** Baseline and 1 Week Post Treatment (8-10 weeks) #### Secondary Outcomes **Description:** The Quick Inventory of Depressive Symptomology (QIDS) is a 16 item self-report measure of depression severity. Scores range from 0 to 27, with higher scores indicating greater severity of depression. **Measure:** Change in depression, as measured by the Quick Inventory of Depressive Symptomology (QIDS) **Time Frame:** Baseline and Post Treatment (7-9 weeks) **Description:** Calculated from Functional Magnetic Resonance Imaging (fMRI) scan conducted while participant is awake but not completing any tasks in the scanner. Used to determine biotype of depression for treatment assignment and to determine if any changes in resting state connectivity have taken place post-TMS treatment. **Measure:** Change in Resting State fMRI Connectivity **Time Frame:** Baseline and after completion of treatment (7-9 weeks) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age 22 to 65 years * Major Depressive Disorder (by M.I.N.I., Diagnostic Statistical Manual V (DSM-V criteria)); Verification by evaluation by licensed study psychiatrist or psychologist * At least moderately severe depression (17-item Hamilton Depression Rating Scale greater than or equal to 18) * Failure to respond in the current episode to at least 1 antidepressant medication at an adequate dose and duration as measured by a modified Antidepressant Treatment History Form. The Maudsley Staging Method will also be used to quantify treatment resistance. * Any and all medication intended to treat depression or reduce symptoms of depression must be discontinued or maintained at the same daily dose for ≥ 4 weeks prior to enrollment and for the duration of the study * Capacity to consent * Written consent to allow communication between members of the research team and the patient's outpatient clinician(s) (psychiatrist, psychotherapist, nurse practitioner, primary care physician, or equivalent) as needed to ensure safety * Ability to safely participate in MRI * Fluent in English Exclusion Criteria: * Imminent risk of suicide (based on the Columbia-Suicide Severity Rating Scale) * Current depressive episode greater than or equal to 2 years duration * Presence of primary psychiatric diagnoses other than MDD and/or comorbid generalized anxiety disorder (GAD) or phobia (e.g., post-traumatic stress disorder; obsessive-compulsive disorder; MDD w psychotic features; primary psychotic illness; Bipolar I or II) * DSM-5 defined addiction to, dependence on, abuse of, or misuse of any substance during the prior 12 months, excluding nicotine * Evidence of cognitive impairment (MMSE score falling greater than or equal to 1 SD below the mean score for his or her age and education) * Recent onset (within 8 weeks of screening) psychotherapy, including, but not limited to: any form of treatment, aid, or therapy that has intensively and extensively examined the patient's psychological history, including, but not limited to: cognitive behavioral therapy, dialectical behavioral therapy, interpersonal therapy, and family-focused therapy * Prior exposure to an adequate dose and duration of the TMS treatment protocol administered in this study during the current depressive episode. * Participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening * History of neurosurgery to treat a neurological or psychiatric disorder * Evidence or history of significant neurological disorder, including moderate-severe head trauma, stroke, Parkinson's disease or other movement disorder (except benign essential tremor), epilepsy, history of seizures, cerebrovascular disease, dementia, increased intracranial pressure, history of repetitive or severe head trauma, or primary or secondary tumors within the central nervous system * Implanted electronic devices and/or conductive objects in or near the head, including metal plates, aneurysm coils, cochlear implants, ocular implants, deep brain stimulation devices and stents * Any implanted device that is activated or controlled in any way by physiological signals, including, but not limited to: deep brain stimulators, cochlear implants, and vagus nerve stimulators * Patients with major depressive disorder who have failed to receive clinical benefit from Vagus Nerve Stimulation (VNS) or are currently receiving these therapies. * History of seizures (except juvenile febrile seizures) or any condition/concurrent medication that could notably lower seizure threshold * Individuals who are pregnant, nursing, contemplating pregnancy within the length of the study or, in the opinion of the investigator, not adherent to a medically acceptable method of birth control * History or presence of any disease, medical condition or physical condition that, in the opinion of the investigator, may compromise, interfere, limit, effect, or reduce the participant's ability to complete a treatment study lasting up to 21 weeks * Abnormal bloodwork for electrolytes, thyroid and liver function * Individuals who are taking \> 300 mg daily dose of bupropion in any formulation (immediate, extended, or slow-release) * Individuals who are taking tricyclic antidepressants. **Maximum Age:** 65 Years **Minimum Age:** 22 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Megan Johnson **Phone:** 646-962-2900 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Lindsay Victoria, PhD **Role:** CONTACT #### Locations **Location 1:** **City:** Stanford **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Derrick Buchanan, PhD - **Role:** CONTACT **Country:** United States **Facility:** Stanford University **State:** California **Status:** RECRUITING **Zip:** 94305 **Location 2:** **City:** New York **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Conor Liston, MD, PhD - **Phone:** 646-962-6293 - **Role:** CONTACT **Country:** United States **Facility:** Weill Cornell Medicine **State:** New York **Status:** RECRUITING **Zip:** 10065 #### Overall Officials **Official 1:** **Affiliation:** Weill Medical College of Cornell University **Name:** Conor Liston, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** The data may be shared with researchers at institutions with a Federal Wide Assurance, who will be able to gain access to NDCT data by submitting a data access request, in line with NDCT policies. **Description:** In accordance with NIH policy we will share our data via the National Database for Clinical Trials related to Mental Illness (NDCT). NDCT is a secure data platform that will allow us to share research data and tools from our analysis of resting-state fMRI data, task-based fMRI data, and fMRI-guided rTMS data. Specifically, data to be shared will include de-identified neuroimaging scans and rTMS targeting data, in addition to phenotypic data such as demographics, diagnosis, treatment history, and anonymized, item-level responses to clinical and cognitive assessments. These data will then be made available through the NDCT, and NIH-funded repository that ensures that data are secure and shared in accord with applicable NIH regulations. **IPD Sharing:** YES **Time Frame:** Raw data (e.g., MRI data and assessment responses) will be deposited on the NDCT every six months (January 15 and June 15 of each year of the award period), in accordance with NIH policy for use of the NDCT in clinical trials research. Curated data will be uploaded annually beginning in the third year of the project. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001526 - Term: Behavioral Symptoms - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depression - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depression - ID: M7060 - Name: Depressive Disorder, Major - Relevance: HIGH - As Found: Major Depressive Disorder - ID: M29783 - Name: Depressive Disorder, Treatment-Resistant - Relevance: HIGH - As Found: Treatment Resistant Depression - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003863 - Term: Depression - ID: D000003866 - Term: Depressive Disorder - ID: D000003865 - Term: Depressive Disorder, Major - ID: D000061218 - Term: Depressive Disorder, Treatment-Resistant ### Misc Info Module #### Removed Countries - Country: Canada - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02702479 **Brief Title:** Meta-analyses of the Effect of Sucrose Versus High Fructose Corn Syrup on Cardiometabolic Risk **Official Title:** Effect of Sucrose Versus High Fructose Corn Syrup on Cardiometabolic Risk: A Series of Systematic Reviews and Meta-Analyses of Controlled Trials #### Organization Study ID Info **ID:** CIHR-Surose vs HFCS #### Organization **Class:** OTHER **Full Name:** University of Toronto ### Status Module #### Completion Date **Date:** 2016-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2016-05-17 **Type:** ESTIMATED **Last Update Submit Date:** 2016-05-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2016-06 **Type:** ESTIMATED #### Start Date **Date:** 2014-06 **Status Verified Date:** 2016-05 #### Study First Post Date **Date:** 2016-03-08 **Type:** ESTIMATED **Study First Submit Date:** 2016-03-02 **Study First Submit QC Date:** 2016-03-02 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** Canadian Institutes of Health Research (CIHR) **Class:** OTHER **Name:** The Physicians' Services Incorporated Foundation **Class:** OTHER **Name:** Banting & Best Diabetes Centre #### Lead Sponsor **Class:** OTHER **Name:** University of Toronto #### Responsible Party **Investigator Affiliation:** University of Toronto **Investigator Full Name:** John Sievenpiper **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The rise in high fructose corn syrup (HFCS) consumption over the past 40 years since its introduction as a popular sweetener in the United States has led to much concern regarding its contribution to the rise in obesity (1), diabetes (2) and related cardiometabolic disorders (3).Unlike sucrose which contains equal proportions of fructose and glucose bound by an α-glycosidic bond, HFCS contains 42-55% of fructose to glucose in a free (unbound) form (4). Despite these differences in composition, both sugars possess identical energy contribution on a gram to gram basis (4). However, the higher ratio of fructose to glucose in HFCS has led to the hypothesis that HFCS may uniquely contribute to cardiometabolic risk, more so than sucrose, through proposed differences in fructose metabolism, endocrine and hedonic properties (5). We will conduct a series of systematic reviews and meta-analyses to assess the role of HFCS versus sucrose under energy matched (isocaloric) conditions on cardiometabolic risk. **Detailed Description:** Need for proposed research: High quality systematic reviews and meta-analyses of controlled trials represent the highest level of evidence to support dietary guidelines and public health policy development. As HFCS has gained increasing popularity as a popular sweetener over the past \~50 years, replacing sucrose in the diet, there is an urgent need for systematic reviews and meta-analyses comparing sucrose versus HFCS in the development of cardiometaboilc diseases. Objective: The investigators will conduct a series systematic reviews and meta-analyses to distinguish the effect of isocaloric exchange of sucrose versus HFCS on cardiometabolic risk in controlled trials. Design: Each systematic review and meta-analysis will be conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data sources: MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (Clinical Trials; CENTRAL) will be searched using appropriate search terms supplemented by hand searches of references of included studies. Study selection: The investigators will include randomized and non-randomized controlled trials \>= 7-days in duration to assess the effect of sucrose versus HFCS under isocaloric conditions on measures of cardiometabolic risk. Direct comparisons of sucrose versus HFCS and indirect comparisons of sucrose or HFCS versus other carbohydrates under energy-matched conditions will be conducted. Data extraction: Two or more investigators will independently extract relevant data and assess risk of bias using the Cochrane Risk of Bias Tool. All disagreements will be resolved by consensus. Standard computations and imputations will be used to derive missing variance data. Outcomes: Seven sets of outcomes will be assessed: (1) body weight and markers of adipsoity (2) glycemic control, (3) blood pressure, (4) blood lipids, (5) uric acid, (6) non-alcoholic fatty liver disease (NAFLD) and ectopic fat, (7) inflammation Data synthesis: Mean differences will be pooled using the generic inverse variance method when data are available from more than 2 trials. Random-effects models will be used even in the absence of statistically significant between-study heterogeneity, as they yield more conservative summary effect estimates in the presence of residual heterogeneity. Fixed-effects models will only be used where there is \<5 included studies. Paired analyses will be applied for crossover trials. Heterogeneity will be assessed by the Cochran Q statistic and quantified by the I2 statistic. To explore sources of heterogeneity, the investigators will conduct sensitivity analyses, in which each study is systematically removed. If there are \>=10 studies per endpoint, then the investigators will also explore sources of heterogeneity by a priori subgroup analyses by age (children \[=\<18 years of age\], adults), health status (metabolic syndrome criteria, diabetes, overweight/ obese, healthy), comparator type, fructose- containing sugar form (sucrose, HFCS, honey, fructose), dose (=\<10% energy, \>10% energy), baseline measurements, randomization, study design (parallel, crossover), energy balance (positive, neutral, negative), follow-up (=\<8-weeks, \>8-weeks), and risk of bias. Meta-regression analyses will assess the significance of categorical and continuous subgroups analyses. When \>=10 studies are available, publication bias will be investigated by inspection of funnel plots and formal testing using the Egger's and Begg's tests. If publication bias is suspected, then the investigators will attempt to adjust for funnel plot asymmetry by imputing the missing study data using the Duval and Tweedie trim and fill method. Evidence Assessment: The strength of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Knowledge translation plan: The results will be disseminated through interactive presentations at local, national, and international scientific meetings and publication in high impact factor journals. Target audiences will include the public health and scientific communities with interest in nutrition, diabetes, obesity, and cardiovascular disease. Feedback will be incorporated and used to improve the public health message and key areas for future research will be defined. Applicant/Co-applicant Decision Makers will network among opinion leaders to increase awareness and participate directly as committee members in the development of future guidelines. Significance: The proposed project will aid in knowledge translation related to the role of sucrose versus HFCS in the development of cardiometabolic diseases, strengthening the evidence-base for guidelines and improving health outcomes by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design. ### Conditions Module **Conditions:** - Obesity - Dyslipidemia - Prediabetes - Dysglycemia - Gout - Hypertension - Non-Alcoholic Fatty Liver Disease - Cardiovascular Disease **Keywords:** - Systematic review and meta-analysis - Evidence-based medicine (EBM) - Evidence-based nutrition (EBN) - Clinical practice guidelines - Clinical trials - Dietary sugars - Fructose - High fructose corn syrup - Isocaloric - Hypercaloric - Cardiometabolic Risk Factors - Triglycerides - Cholesterol - Glycemic control - Body weight - Uric acid - Blood pressure - Fatty liver - Fasting - Postprandial ### Design Module #### Enrollment Info **Count:** 1 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** An intervention in which calories from HFCS are substituted isocalorically for sucrose in the diet **Name:** High Fructose Corn Syrup **Other Names:** - HFCS **Type:** OTHER #### Intervention 2 **Description:** An intervention in which calories from sucrose are substituted isocalorically for HFCS in the diet **Name:** Sucrose **Other Names:** - sugar **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** Body weight and measures of adiposity analysis **Time Frame:** Up to 20 years **Measure:** Glycemic control analysis **Time Frame:** Up to 20 years **Measure:** Blood Lipids analysis **Time Frame:** Up to 20 years **Measure:** Blood pressure analysis **Time Frame:** Up to 20 years **Measure:** Uric acid analysis **Time Frame:** Up to 20 years **Measure:** Non-Alcoholic Fatty Liver Disease (NAFLD) and ectopic fat Analysis **Time Frame:** Up to 20 years **Measure:** Inflammation analysis **Time Frame:** Up to 20 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Trials in humans * Oral fructose-containing sugars intervention * Presence of an adequate comparator in isocaloric substitution * Diet duration \>=7 days * Viable outcome data Exclusion Criteria: * Non-human trials * Observational studies * IV or parenteral fructose-containing sugars * Lack of suitable comparator (i.e. a comparator arm not including sucrose or HFCS in isocaloric substitution) * Diet duration \<7 days * No viable outcome data **Healthy Volunteers:** True **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** All individuals, both children and adults, regardless of health status. ### Contacts Locations Module #### Locations **Location 1:** **City:** Toronto **Country:** Canada **Facility:** The Toronto 3D (Diet, Digestive tract and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital **State:** Ontario **Zip:** M5C 2T2 #### Overall Officials **Official 1:** **Affiliation:** University of Toronto **Name:** John L Sievenpiper, MD,PhD,FRCPC **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004066 - Term: Digestive System Diseases - ID: D000052439 - Term: Lipid Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M14117 - Name: Prediabetic State - Relevance: LOW - As Found: Unknown - ID: M26181 - Name: Dyslipidemias - Relevance: HIGH - As Found: Dyslipidemia - ID: M11107 - Name: Liver Diseases - Relevance: HIGH - As Found: Liver Disease - ID: M8375 - Name: Fatty Liver - Relevance: HIGH - As Found: Fatty Liver - ID: M30540 - Name: Non-alcoholic Fatty Liver Disease - Relevance: HIGH - As Found: Non-alcoholic Fatty Liver Disease - ID: M9177 - Name: Gout - Relevance: LOW - As Found: Unknown - ID: M20295 - Name: Glucose Intolerance - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M27029 - Name: Lipid Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: T5868 - Name: Visceral Steatosis - Relevance: HIGH - As Found: Fatty Liver ### Condition Browse Module - Meshes - ID: D000008107 - Term: Liver Diseases - ID: D000005234 - Term: Fatty Liver - ID: D000065626 - Term: Non-alcoholic Fatty Liver Disease - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000050171 - Term: Dyslipidemias ### Intervention Browse Module - Browse Branches - Abbrev: Hemat - Name: Hematinics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M17277 - Name: Uric Acid - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT00423579 **Brief Title:** The Effects of Ezetimibe/Simvastatin 10/20 mg Versus Simvastatin 40 mg in High Cholesterol and Coronary Heart Disease Study (P04039AM2)(COMPLETED) **Official Title:** A Multicenter, Randomized, Parallel-Groups, Double-Blind Placebo-Controlled Study Comparing the Efficacy, Safety, and Tolerability of Administration of Ezetimibe/Simvastatin Tablet 10/20 mg Versus Doubling the Dose of Simvastatin 20 mg [Simvastatin 40 mg] in Subjects With Primary Hypercholesterolemia and Coronary Heart Disease #### Organization Study ID Info **ID:** P04039 #### Organization **Class:** INDUSTRY **Full Name:** Organon and Co ### Status Module #### Completion Date **Date:** 2008-03-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-22 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-08 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-03-01 **Type:** ACTUAL #### Results First Post Date **Date:** 2009-08-25 **Type:** ESTIMATED **Results First Submit Date:** 2009-03-19 **Results First Submit QC Date:** 2009-07-16 #### Start Date **Date:** 2006-07-01 **Type:** ACTUAL **Status Verified Date:** 2022-02 #### Study First Post Date **Date:** 2007-01-18 **Type:** ESTIMATED **Study First Submit Date:** 2007-01-17 **Study First Submit QC Date:** 2007-01-17 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Schering-Plough #### Lead Sponsor **Class:** INDUSTRY **Name:** Organon and Co #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is being conducted to compare the efficacy, safety, and tolerability of ezetimibe/simvastatin 10/20 mg when administered daily versus doubling the dose of simvastatin to 40 mg in patients with hypercholesterolemia and coronary heart disease. ### Conditions Module **Conditions:** - Hypercholesterolemia - Coronary Disease ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 120 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin 10/20 mg. The second tablet is simvastatin placebo. Subjects will receive a maximum of 6 weeks of treatment **Intervention Names:** - Drug: Ezetimibe/Simvastatin 10/20 mg **Label:** Ezetimibe/Simvastatin 10/20 mg + Simvastatin placebo **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin placebo. The second tablet is simvastatin 40 mg. Subjects will receive a maximum of 6 weeks of treatment. **Intervention Names:** - Drug: simvastatin 40 mg **Label:** Ezetimibe/Simvastatin placebo + Simvastatin 40 mg **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Ezetimibe/Simvastatin 10/20 mg + Simvastatin placebo **Description:** 1 tablet containing 10 mg of ezetimibe and 20 mg of simvastatin per day for 6 weeks **Name:** Ezetimibe/Simvastatin 10/20 mg **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Ezetimibe/Simvastatin placebo + Simvastatin 40 mg **Description:** 1 tablet containing 40 mg of simvastatin per day for 6 weeks **Name:** simvastatin 40 mg **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Percentage change in LDL C from baseline to endpoint after 6 weeks of treatment. **Measure:** Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks **Time Frame:** Baseline and 6 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects must have documented coronary heart disease (CHD). For the purposes of this study, CHD will include one or more of the following features: documented stable angina (with evidence of ischemia on exercise testing); history of myocardial infarction; history of percutaneous coronary intervention \[PCI\] (primarily PCI with or without stent placement); symptomatic peripheral vascular disease (claudication); documented history of atherothrombotic cerebrovascular disease; and/or documented history of unstable angina or non-Q wave myocardial infarction. * Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent. * History of myocardial infarction (heart attack). * Subjects must be \>= 18 years and \<= 75 years of age. * Subjects must have an LDL-C concentration \>= 2.6 mmol/L (100 mg/dL) to \<= 4.1 mmol/L (160 mg/dL) at the time of randomization (Visit 3/Baseline Visit). * Subjects must have triglyceride concentrations of \< 3.99 mmol/L (350 mg/dL) at (Visit 3 Baseline Visit). * Subject must be currently taking simvastatin 20 mg daily. * Subjects must have liver transaminases (ALT \[alanine aminotransferase\], AST \[aspartate aminotransferase\]) \< 50% above the upper limit of normal, with no active liver disease, and CK (creatine kinase) \< 50% above the upper limit of normal at Visit 3 (Baseline Visit). * Clinical laboratory tests (complete blood count \[CBC\], blood chemistries, urinalysis) must be within normal limits or clinically acceptable to the investigator at Visit 3 (Baseline Visit). * Subjects must have maintained a cholesterol-lowering diet and exercise program for at least 4 weeks prior to the study and be willing to continue the same diet and exercise program during the study. * Subjects must report a stable weight history for at least 4 weeks prior to entry into study at Visit 3 (Baseline Visit). * Women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study. * Women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed intrauterine device \[IUD\], condom in combination with spermicide) or be surgically sterilized (e.g., hysterectomy or tubal ligation). * Subjects must be free of any clinically significant diseases other than hyperlipidemia or coronary heart disease that would interfere with study evaluations. * Subjects must understand and be able to adhere to the dosing and visit schedules, and must agree to remain on their cholesterol-lowering diet and their exercise regimen for the duration of the study. Exclusion Criteria: * Subjects whose body mass index (BMI = weight \[kg\]/height2 \[m\]) is \>= 35 kg/m\^2 at Visit 3 (Baseline Visit). * Subjects who consume \> 14 alcoholic drinks per week. (A drink is: a can of beer, glass of wine, or single measure of spirits). * Any condition or situation which, in the opinion of the investigator, might pose a risk to the subject or interfere with participation in the study. * Women who are pregnant or nursing. Exclusion Criteria: subjects who have the following medical conditions: * Congestive heart failure defined by New York Heart Association (NYHA) as Class III or IV. * Uncontrolled cardiac arrhythmia. * Myocardial infarction, acute coronary insufficiency, coronary artery bypass surgery, or angioplasty within 3 months of Visit 3 (Baseline Visit). * Unstable or severe peripheral artery disease within 3 months of Visit 3 (Baseline Visit). * Newly diagnosed or currently unstable angina pectoris (chest pain). * Uncontrolled hypertension (treated or untreated) with systolic blood pressure \> 160 mm Hg or diastolic \> 100 mm Hg at Visit 3 (Baseline Visit). * Type I or Type II diabetes mellitus. * Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins, i.e., secondary causes of hyperlipidemia, such as secondary hypercholesterolemia due to hypothyroidism (thyroid stimulating hormone \[TSH\] above upper limit of normal) at Visit 3. Subjects with a history of hypothyroidism who are on a stable therapy of thyroid hormone replacement for at least 6 weeks are eligible for enrollment if TSH levels are within normal limits at Visit 3 (Baseline Visit). * Impaired renal function (creatinine \> 2.0 mg/dL) or nephrotic syndrome at Visit 3 (Baseline Visit). * Disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation. * Known Human Immunodeficiency Virus (HIV) positive. * Cancer within the past 5 years (except for successfully treated basal and squamous cell carcinomas). * History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy. Exclusion Criteria: subjects who are on any of the following concomitant medications: * Subjects who have not observed the designated wash-out period for any of the prohibited medications. * Subjects who have not stopped taking various prohibited medications for a minimum period of time before Visit 3, including amiodarone hydrochloride (6 months) and probucol (12 months). * Subjects currently consuming large amounts of grapefruit juice (\> 1 liter/day). * Oral corticosteroids, unless used as replacement therapy for pituitary/adrenal disease and the subject is on a stable regimen for at least 6 weeks prior to Visit 3 (Baseline Visit). * Subjects who are currently using cardiovascular medication (e.g. antihypertensive, antiarrhythmic) and have not been on a stable regimen for at least 6 weeks prior to Visit 3 (Baseline Visit) and it is expected to change during the study. * Subjects who are currently using psyllium, other fiber-based laxatives, and/or any other over-the-counter (OTC) therapy known to affect serum lipid levels (phytosterol margarine), and have not been on a stable regimen for at least 5 weeks prior to study entry Visit 3 (Baseline Visit) and who do not agree to remain on this regimen throughout the study. * Subject who are currently using orlistat or sibutramine. * Subjects who are currently using amiodarone hydrochloride. * Subjects who are currently using danazol. * Subjects who are currently using coumarin anticoagulants (warfarin). * Subjects who are using (at the Screening Visit / Visit 1) any statin other than simvastatin 20 mg, or ezetimibe alone or in combination with any statin (including the fixed combination with simvastatin). **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Averna M, Zaninelli A, Le Grazie C, Gensini GF. Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients. J Clin Lipidol. 2010 Jul-Aug;4(4):272-8. doi: 10.1016/j.jacl.2010.05.002. Epub 2010 Jun 1. **PMID:** 21122660 **Citation:** Rotella CM, Zaninelli A, Le Grazie C, Hanson ME, Gensini GF. Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes. Lipids Health Dis. 2010 Jul 27;9:80. doi: 10.1186/1476-511X-9-80. **PMID:** 20663203 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000006949 - Term: Hyperlipidemias - ID: D000050171 - Term: Dyslipidemias - ID: D000052439 - Term: Lipid Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000001161 - Term: Arteriosclerosis - ID: D000001157 - Term: Arterial Occlusive Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M9419 - Name: Heart Diseases - Relevance: HIGH - As Found: Heart Disease - ID: M6549 - Name: Coronary Disease - Relevance: HIGH - As Found: Coronary Disease - ID: M6546 - Name: Coronary Artery Disease - Relevance: HIGH - As Found: Coronary Heart Disease - ID: M19506 - Name: Myocardial Ischemia - Relevance: HIGH - As Found: Coronary Heart Disease - ID: M9988 - Name: Hypercholesterolemia - Relevance: HIGH - As Found: Hypercholesterolemia - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M10000 - Name: Hyperlipidemias - Relevance: LOW - As Found: Unknown - ID: M10002 - Name: Hyperlipoproteinemias - Relevance: LOW - As Found: Unknown - ID: M26181 - Name: Dyslipidemias - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M27029 - Name: Lipid Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M4469 - Name: Arteriosclerosis - Relevance: LOW - As Found: Unknown - ID: M4465 - Name: Arterial Occlusive Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006331 - Term: Heart Diseases - ID: D000003327 - Term: Coronary Disease - ID: D000003324 - Term: Coronary Artery Disease - ID: D000017202 - Term: Myocardial Ischemia - ID: D000006937 - Term: Hypercholesterolemia ### Intervention Browse Module - Ancestors - ID: D000000924 - Term: Anticholesteremic Agents - ID: D000000960 - Term: Hypolipidemic Agents - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000057847 - Term: Lipid Regulating Agents - ID: D000019161 - Term: Hydroxymethylglutaryl-CoA Reductase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Lipd - Name: Lipid Regulating Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21713 - Name: Simvastatin - Relevance: HIGH - As Found: Being - ID: M409 - Name: Ezetimibe - Relevance: HIGH - As Found: Amount - ID: M450 - Name: Ezetimibe, Simvastatin Drug Combination - Relevance: HIGH - As Found: Cyclophosphamide 50 mg - ID: M4243 - Name: Anticholesteremic Agents - Relevance: LOW - As Found: Unknown - ID: M4278 - Name: Hypolipidemic Agents - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M28883 - Name: Lipid Regulating Agents - Relevance: LOW - As Found: Unknown - ID: M21155 - Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000019821 - Term: Simvastatin - ID: D000069438 - Term: Ezetimibe - ID: D000069499 - Term: Ezetimibe, Simvastatin Drug Combination ### Misc Info Module #### Removed Countries - Country: Italy - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Ezetimibe/Simvastatin 10/20 mg + Simvastatin Placebo **Description:** Subjects in the Intent-to-Treat Population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin 10/20 mg. The second tablet is simvastatin placebo. Subjects will receive a maximum of 6 weeks of treatment **ID:** EG000 **Other Num at Risk:** 60 **Serious Number At Risk:** 60 **Title:** Ezetimibe/Simvastatin 10/20 mg + Simvastatin Placebo **Group ID:** EG001 **Title:** Ezetimibe/Simvastatin Placebo + Simvastatin 40 mg **Description:** Subjects in the Intent-to-Treat population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin placebo. The second tablet is simvastatin 40 mg. Subjects will receive a maximum of 6 weeks of treatment. **ID:** EG001 **Other Num at Risk:** 60 **Serious Number Affected:** 1 **Serious Number At Risk:** 60 **Title:** Ezetimibe/Simvastatin Placebo + Simvastatin 40 mg **Frequency Threshold:** 5 #### Serious Events **Term:** Transient Ischemic Attack **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 60 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 60 **Num Events:** 1 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 56 **Group ID:** BG001 **Value:** 56 **Group ID:** BG002 **Value:** 112 **Units:** Participants ### Group **ID:** BG000 **Title:** Ezetimibe/Simvastatin 10/20 mg + Simvastatin Placebo **Description:** Subjects in the Intent-to-Treat Population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin 10/20 mg. The second tablet is simvastatin placebo. Subjects will receive a maximum of 6 weeks of treatment ### Group **ID:** BG001 **Title:** Ezetimibe/Simvastatin Placebo + Simvastatin 40 mg **Description:** Subjects in the Intent-to-Treat population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin placebo. The second tablet is simvastatin 40 mg. Subjects will receive a maximum of 6 weeks of treatment. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 8.4 **Value:** 61.3 #### Measurement **Group ID:** BG001 **Spread:** 7.8 **Value:** 62.1 #### Measurement **Group ID:** BG002 **Spread:** 8.1 **Value:** 61.7 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 26 #### Measurement **Group ID:** BG001 **Value:** 24 #### Measurement **Group ID:** BG002 **Value:** 50 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 30 #### Measurement **Group ID:** BG001 **Value:** 32 #### Measurement **Group ID:** BG002 **Value:** 62 **Category Title:** Male **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Description:** Mean age based on Intent-to-Treat population. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Description:** Gender totals based on Intent-to-Treat population. **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Other Details:** The investigator shall not publish or publicly present the study results without prior written authorization from the sponsor, except for dispositions in the Ministerial Circular n. 6 dated 02 SEP 2002. The investigator shall notify the sponsor in writing of any publication submission or presentation reporting results of the study 30 days prior to submission or presentation to permit sponsor review. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Merck Sharp & Dohme Corp. **Title:** Senior Vice President, Global Clinical Development ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -18.9 **CI Number of Sides:** **CI Percentage Value:** 95 **CI Upper Limit:** -10.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Difference in percentage change in mean LDL-C values (change from baseline to week 6) between the two treatment groups. (Ezetimibe \[EZ\]/Simvastatin \[S\] \[10/20mg\] + S \[placebo\] group minus the EZ/S \[10mg/placebo\] + S \[40mg\] group) **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.0000 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** -14.5 **Statistical Comment:** **Statistical Method:** Student's t test for independent data **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.5 - **Upper Limit:** - **Value:** -26.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.6 - **Upper Limit:** - **Value:** -11.9 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Percentage change in LDL C from baseline to endpoint after 6 weeks of treatment. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Intent-to-treat population only. **Reporting Status:** POSTED **Time Frame:** Baseline and 6 weeks **Title:** Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks **Type:** PRIMARY **Unit of Measure:** percentage change ##### Group **Description:** Subjects in the Intent-to-Treat Population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin 10/20 mg. The second tablet is simvastatin placebo. Subjects will receive a maximum of 6 weeks of treatment **ID:** OG000 **Title:** Ezetimibe/Simvastatin 10/20 mg + Simvastatin Placebo ##### Group **Description:** Subjects in the Intent-to-Treat population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin placebo. The second tablet is simvastatin 40 mg. Subjects will receive a maximum of 6 weeks of treatment. **ID:** OG001 **Title:** Ezetimibe/Simvastatin Placebo + Simvastatin 40 mg ### Participant Flow Module #### Group **Description:** Subjects in the Intent-to-Treat Population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin 10/20 mg. The second tablet is simvastatin placebo. Subjects will receive a maximum of 6 weeks of treatment **ID:** FG000 **Title:** Ezetimibe/Simvastatin 10/20 mg + Simvastatin Placebo #### Group **Description:** Subjects in the Intent-to-Treat population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin placebo. The second tablet is simvastatin 40 mg. Subjects will receive a maximum of 6 weeks of treatment. **ID:** FG001 **Title:** Ezetimibe/Simvastatin Placebo + Simvastatin 40 mg #### Period **Title:** Overall Study ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Diagnosis of diabetes ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 60 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 60 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 56 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 56 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 4 **Pre-Assignment Details:** Visits 1 and 2 were for screening, combined if wash-out not required. One ineligible subject mistakenly received assignment at Visit 2 and was removed. The subject did not receive treatment. Actual enrollment: 120 subjects. Intent-to-treat (ITT) population included only evaluable subjects; as such analysis based on 112 subjects. **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT04990479 **Brief Title:** Nous-PEV: a Novel Immunotherapy for Lung Cancer and Melanoma **Official Title:** An Open-Label, Multicenter, Non-Randomized, Dose-Confirmation and Cohort-Expansion Phase 1b Study to Evaluate the Safety, Tolerability, and Anti-Tumor Activity of Nous-PEV, With Pembrolizumab, in Patients With Unresectable Stage III / IV Cutaneous Melanoma and With Stage IV NSCLC (PDL1≥ 50%) #### Organization Study ID Info **ID:** NOUS-PEV-01 #### Organization **Class:** INDUSTRY **Full Name:** Nouscom SRL #### Secondary ID Infos **ID:** 2019-004759-35 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2024-10-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-03-13 **Type:** ACTUAL **Last Update Submit Date:** 2023-03-09 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-10-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-06-11 **Type:** ACTUAL **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2021-08-04 **Type:** ACTUAL **Study First Submit Date:** 2021-07-15 **Study First Submit QC Date:** 2021-07-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Nouscom SRL #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** From Protocol v3.0 dated 16Jun2022. This is an international, multicenter, open-label, multiple cohort, First in Human, phase 1b clinical study, designed to evaluate safety, tolerability, and immunogenicity, and to detect any preliminary evidence of anti-tumor activity of a personalized vaccine (PEV) based on GAd-PEV priming and MVA-PEV boosting, combined with SoC first-line immunotherapy using an anti-PD-1 checkpoint inhibitor in patients with unresectable stage III/IV cutaneous melanoma or with stage IV NSCLC (PDL1 ≥ 50%). The PEV vaccines will be prepared on an individual basis, following a tumor biopsy performed at the time of screening and subsequent NGS analysis, to identify patient-specific tumor mutations. Both neoantigen-encoding genetic vaccines are administered intramuscularly using 1 prime with GAd-PEV and 3 boosts with MVA-PEV in combination with the licensed programmed death receptor-1 (PD-1)-blocking antibody pembrolizumab in adult patients in patients with unresectable stage III/IV cutaneous melanoma (Cohort a) or with stage IV NSCLC (PDL1 ≥ 50%) (Cohort b). **Detailed Description:** Overall Study Design: • This is an open-label, non-randomized, dose-confirmation and cohort expansion phase 1b first-in-human study, in which 28 patients, expandable up to 34 evaluable patients in case of DLT. Study IMPs: Nous-PEV vaccine is composed of 2 sets of IMPs: * GAd-PEV * MVA-PEV Treatment phases: A) Induction phase with pembrolizumab (cycles 1, 2 and 3). B) Priming phase including 1 GAd-PEV administration with pembrolizumab (cycle 4). C) Boosting phase including 3 boosting administrations of MVA-PEV with pembrolizumab (cycles 5, 6 and 7). ### Conditions Module **Conditions:** - Melanoma (Skin) - Non-Small-Cell Lung Carcinoma ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SEQUENTIAL **Intervention Model Description:** Treatment Cohorts of the study. Part 1: • Cohort 1a: 3 patients (expandable to 9) with unresectable stage III / IV Cutaneous Melanoma. Part 2 * Cohort 2a: 13 patients with unresectable stage III / IV Cutaneous Melanoma. * Cohort 2b:12 patients with stage IV NSCLC (PDL1≥ 50%). In all cohorts, the treatment consists of four Nous-PEV vaccine administrations in combination with pembrolizumab as SoC. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 34 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Cohort 1a: 3 patients (expandable to 9) with unresectable stage III / IV Cutaneous Melanoma. **Intervention Names:** - Biological: GAd-PEV - Biological: MVA-PEV **Label:** Cohort 1a **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Cohort 2a:13 patients with unresectable stage III / IV Cutaneous Melanoma. **Intervention Names:** - Biological: GAd-PEV - Biological: MVA-PEV **Label:** Cohort 2a **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Cohort 2b: 12 patients with stage IV NSCLC (PDL1≥ 50%). **Intervention Names:** - Biological: GAd-PEV - Biological: MVA-PEV **Label:** Cohort 2b **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Cohort 1a - Cohort 2a - Cohort 2b **Description:** Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab (cycle 4). **Name:** GAd-PEV **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Cohort 1a - Cohort 2a - Cohort 2b **Description:** Boosting phase including 3 boosting administrations of MVA-PEV with Standard of Care pembrolizumab (cycles 5, 6 and 7). **Name:** MVA-PEV **Type:** BIOLOGICAL ### Outcomes Module #### Other Outcomes **Description:** PBMC-derived T-cell responses against vaccine FSPs, as measured by IFN-gamma ELISpot **Measure:** Exploratory outcome: immunogenicity **Time Frame:** Up to 110 weeks #### Primary Outcomes **Description:** * Frequency, duration, and severity of adverse events (AEs) and serious adverse events (SAEs) using CTCAE v5.0 criteria. * Changes in vital signs and clinical evaluations. * Changes in clinical laboratory blood samples. * Dose-limiting toxicity (DLT) **Measure:** Safety and tolerability: incidence of treatment- emerging adverse events. AEs characterized by type, severity (graded by CTCAE v.5.0), Timing, seriousness and relationship to study treatments. **Time Frame:** Up to 110 weeks #### Secondary Outcomes **Description:** RP2D confirmation based on safety and tolerability **Measure:** RP2D confirmation 2. Clinical efficacy: **Time Frame:** Up to 110 weeks **Description:** Clinical efficacy based on Overall response rate (ORR); Best overall response (BOR); Duration of response (DoR); Progression-free survival (PFS); Overall survival (OS), all as defined in tumor imaging, RECIST 1.1 **Measure:** Clinical efficacy **Time Frame:** Up to 110 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Main Inclusion Criteria for Patients in Cohorts 1a and 2a: 1. Age ≥ 18 years. 2. Patients with histologically or cytologically confirmed unresectable stage III or stage IV Cutaneous Melanoma, as per AJCC staging system (8th edition). First-line treatment-naive patients. 3. Participation in this trial will be dependent upon supplying tumor tissue from newly obtained specimen. Newly obtained biopsies of a tumor lesion, not previously irradiated, must be provided in the form of excisional biopsies, resected tissue or core needle biopsies. 4. Presence of at least 1 measurable lesion by computed tomography or magnetic resonance imaging per RECIST v1.1 by the local site Investigator / radiologist assessment 5. Presence of at least one lesion amenable to repeated biopsy, ideally not the one being used for measuring. 6. Willingness to undergo a minimum of two fresh lesion biopsies (pre-treatment and on-treatment). 7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. 8. Life expectancy of at least 12 months. 9. Adequate renal, hepatic, and hematologic functions 10. A female patient is eligible to participate if she is not pregnant and not breastfeeding 11. A male patient must agree to use an adequate contraception Main Inclusion Criteria for Patients in Cohort 2b: 1. Age ≥ 18 years. 2. Histologically or cytologically confirmed stage IV squamous or non-squamous NSCLC without EGFR or ALK/ROS1 /RET genomic alteration. 3. Tumor expression with PD-L1 ≥50% tumor proportion score (TPS). 4. First-line treatment-naïve patients. 5. Participation in this trial will be dependent upon supplying tumor tissue from a newly obtained specimen. Newly obtained biopsies of a tumor lesion, not previously irradiated, must be provided in the form of excisional biopsies, resected tissue or core needle biopsies. 6. Presence of at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 as determined by the local site Investigator / radiologist assessment. 7. Presence of at least one tumor lesion amenable to repeated biopsy, if possible, ideally not the one being used for measuring. 8. Willingness to undergo a minimum of two fresh tumor biopsies (pre-treatment and on-treatment). 9. ECOG performance status 0 to 1. 10. Life expectancy of at least 6 months. 11. Adequate renal, hepatic, and hematologic functions 12. A female patient is eligible to participate if she is not pregnant and not breastfeeding 13. A male patient must agree to use a contraceptive during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period. Main Exclusion Criteria for patients in all Cohorts: 1. Currently receiving treatment with another investigational medicinal product. 2. Prior therapy with immune checkpoint inhibitors. Patients must not have received any investigational immunotherapy either. 3. Prior radiotherapy within 2 weeks of enrolment, or within 4 weeks of enrolment in the case of radiation to central nervous system (CNS), which requires ≥ 4-week washout. 4. Prior allogenic tissue or solid organ transplant. 5. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids and/or whose pulse oximetry is less than 92% "on room air". 6. Limiting cardiac criteria: prolonged QT interval or QT prolongation risk factors, clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g. complete LBBB, third degree heart block, risk of arrythmic events, ejection fraction under lower limit of normal. 7. Major (according to the Investigator's judgment) surgery within 12 weeks before enrolment. 8. Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry. 9. Immunosuppression including the continued use of systemic (at prednisone dose equivalent of \> 10 mg) or topical steroids at or near the planned i.m. injection site or the use of immunosuppressive agents for any concurrent condition in the 4 weeks prior to first study treatment administration. Inhaled and eye drop-containing corticosteroids are permitted. 10. Previous vaccination (either therapeutic and/or prophylactic) against cancer. 11. History of autoimmune disease in the last 5 years, including any active autoimmune disease except vitiligo or childhood asthma. 12. Chronic or concurrent active infectious disease requiring systemic antibodies, antifungal, or antiviral treatment. 13. Known Medical History of human immunodeficiency virus (HIV) infection or known Medical History of acquired immunodeficiency syndrome (AIDS). HIV testing is not required unless mandated by the local health authority. 14. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or at risk for HBV reactivation 15. Known CNS metastasis and/or carcinomatous meningitis. 16. Known cerebral edema. 17. Live vaccine received within 30 days before treatment initiation. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Charleroi **Country:** Belgium **Facility:** Grand Hopital de Charleroi, Grand Rue 3, 6000 Charleroi **Zip:** 6000 **Location 2:** **City:** Leuven **Country:** Belgium **Facility:** UZ Leuven Hospital, Campus Gasthuisberg, Herestraat 49, 3000 Leuven **Zip:** 3000 **Location 3:** **City:** Barcelona **Country:** Spain **Facility:** Institut Catalá d'Oncologia ICO L'Hospitalet. Av Gran Via de L'Hospitalet 199-203. 08908 L'Hospitalet de Llobregat, Barcelona, Spain **Zip:** 08908 **Location 4:** **City:** Madrid **Country:** Spain **Facility:** START Madrid - Centro Integral Oncológico Clara Campal, HM CIOCC Hospital Universitario HM Sanchinarro, 28050 Madrid. Spain **Zip:** 28050 **Location 5:** **City:** Madrid **Country:** Spain **Facility:** START Madrid-FJD, Hospital Fundación Jiménez Diaz Avda. Reyes Católicos 2. 28040, Madrid, Spain **Location 6:** **City:** Valencia **Country:** Spain **Facility:** Instituto de Investigación Sanitaria INCLIVA - Hospital Clínico Universitario de Valencia. Av. Blasco Ibáñez, 17 CP 46010 Valencia, Spain **Zip:** 46010 **Location 7:** **City:** Edinburgh **Country:** United Kingdom **Facility:** Cancer Research UK Edinburgh Centre. Western General Hospital, Edinburgh, EH4 2SP, UK **State:** Scotland **Zip:** EH4 2SP #### Overall Officials **Official 1:** **Affiliation:** Nouscom SRL **Name:** Sven Gogov, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Leoni G, D'Alise AM, Tucci FG, Micarelli E, Garzia I, De Lucia M, Langone F, Nocchi L, Cotugno G, Bartolomeo R, Romano G, Allocca S, Troise F, Nicosia A, Lahm A, Scarselli E. VENUS, a Novel Selection Approach to Improve the Accuracy of Neoantigens' Prediction. Vaccines (Basel). 2021 Aug 9;9(8):880. doi: 10.3390/vaccines9080880. **PMID:** 34452005 #### See Also Links **Label:** VENUS is a proprietary algorithm designed to enhance the predictive accuracy of personalized neoantigen selection, used in the NOUS-PEV-01 trial. **URL:** https://pubmed.ncbi.nlm.nih.gov/34452005/ ## Derived Section ### Condition Browse Module - Ancestors - ID: D000018358 - Term: Neuroendocrine Tumors - ID: D000017599 - Term: Neuroectodermal Tumors - ID: D000009373 - Term: Neoplasms, Germ Cell and Embryonal - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009380 - Term: Neoplasms, Nerve Tissue - ID: D000018326 - Term: Nevi and Melanomas - ID: D000012878 - Term: Skin Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000012871 - Term: Skin Diseases - ID: D000008175 - Term: Lung Neoplasms - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M11172 - Name: Lung Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: HIGH - As Found: Non-Small Cell Lung Carcinoma - ID: M11528 - Name: Melanoma - Relevance: HIGH - As Found: Melanoma - ID: M3212 - Name: Melanoma, Cutaneous Malignant - Relevance: LOW - As Found: Unknown - ID: M20495 - Name: Neuroendocrine Tumors - Relevance: LOW - As Found: Unknown - ID: M19845 - Name: Neuroectodermal Tumors - Relevance: LOW - As Found: Unknown - ID: M20388 - Name: Neuroectodermal Tumors, Primitive - Relevance: LOW - As Found: Unknown - ID: M12318 - Name: Neoplasms, Germ Cell and Embryonal - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: M12448 - Name: Nevus, Pigmented - Relevance: LOW - As Found: Unknown - ID: M12446 - Name: Nevus - Relevance: LOW - As Found: Unknown - ID: M20470 - Name: Nevi and Melanomas - Relevance: LOW - As Found: Unknown - ID: M15681 - Name: Skin Neoplasms - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M5260 - Name: Bronchial Neoplasms - Relevance: LOW - As Found: Unknown - ID: T4091 - Name: Neuroendocrine Tumor - Relevance: LOW - As Found: Unknown - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008545 - Term: Melanoma - ID: D000002289 - Term: Carcinoma, Non-Small-Cell Lung ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M349416 - Name: Pembrolizumab - Relevance: LOW - As Found: Unknown - ID: M2853 - Name: Immunomodulating Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT00315679 **Brief Title:** A Trial of Pentoxifylline for the Treatment of Recurrent Aphthous Stomatitis #### Organization Study ID Info **ID:** MHT01 #### Organization **Class:** OTHER_GOV **Full Name:** Manchester University NHS Foundation Trust ### Status Module #### Completion Date **Date:** 1998-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-08-03 **Type:** ACTUAL **Last Update Submit Date:** 2018-08-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 1998-11 **Type:** ACTUAL #### Start Date **Date:** 1996-06 **Status Verified Date:** 2018-08 #### Study First Post Date **Date:** 2006-04-19 **Type:** ESTIMATED **Study First Submit Date:** 2006-04-18 **Study First Submit QC Date:** 2006-04-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Manchester University NHS Foundation Trust ### Description Module **Brief Summary:** This is a randomized, double blind, placebo controlled trial of the use of pentoxifylline (oxpentifylline) for the treatment of recurrent mouth ulcers. **Detailed Description:** There are few effective treatments for recurrent aphthous stomatitis (cancer sores, recurrent mouth ulcers). Most existing treatments are palliative topical treatments. Some systemic drugs e.g. steroids and thalidomide can suppress the recurrence of mouth ulcers but have serious long term side effects. Pentoxifylline (also known as oxpentifylline) has been used systemically for many years to treat peripheral vascular disease and has a good side effect profile. It shares several actions with thalidomide but does not share its serious side effects. Furthermore, some small scale, open label clinical studies have indicated it may be very effective in treating recurrent aphthous stomatitis (RAS). This study enrolled patients with RAS for which no underlying cause could be identified. Patients kept a diary of the pattern of their mouth ulcers for 60 days to confirm the pattern of ulceration and provide baseline data. Those still qualified for the study were then randomized to treatment with pentoxifylline 400mg three times daily or an identical placebo tablet three times daily for a further 60 days during which they continued to keep a daily ulcer diary. At the end of this period, treatment was stopped and they kept the daily ulcer diary for a further 60 days to identify if any benefit from the treatment was continued after ceasing treatment. ### Conditions Module **Conditions:** - Recurrent Aphthous Stomatitis **Keywords:** - recurrent aphthous stomatitis - recurrent mouth ulcers - pentoxifylline - clinical trial - double blind - placebo controlled - randomized ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Pentoxifylline (also known as oxpentifylline) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Reduction in the median pain score **Measure:** Reduction in the median ulcer size **Measure:** Reduction in the median ulcer number **Measure:** Reduction in the total number of episodes of ulceration (RAS) #### Secondary Outcomes **Measure:** Change in global ulcer severity score **Measure:** Increase in the proportion of ulcer free days **Measure:** Difference in the proportion of ulcer free days (comparing trial v baseline) **Measure:** Side effect incidence **Measure:** Side effect type ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosis of minor recurrent aphthous stomatitis * 2 or more mouth ulcers per month for more than 6 * No current treatment for oral ulceration or willing to stop treatment * Age 16 to 65 years Exclusion Criteria: * Taking ketorolac, theophylline or anti-hypertensive medication except diuretics (contra-indicated in patients treated with pentoxifylline) * Systemic diseases that contra-indicate the use of pentoxifylline i.e. pregnancy, hypotension, ischaemic heart disease, acute myocardial infarction, cerebral or occular hemorrhage, renal or hepatic failure, porphyria or allergy to pentoxifylline. * Patients with an underlying deficiency state or systemic disease that could cause recurrent mouth ulcers e.g. iron, vitamin B12 or foliate deficience, coeliac disease, Crohn's disease, ulcerative colitis, Behcet's disease or Aids. **Maximum Age:** 65 Years **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Manchester **Country:** United Kingdom **Facility:** University Dental Hospital of Manchester **Zip:** M15 6FH #### Overall Officials **Official 1:** **Affiliation:** University of Sheffield School of Clinical Dentistry **Name:** Martin H Thornhill, MBBS, BDS **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Thornhill MH, Baccaglini L, Theaker E, Pemberton MN. A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis. Arch Dermatol. 2007 Apr;143(4):463-70. doi: 10.1001/archderm.143.4.463. Erratum In: Arch Dermatol. 2007 Jun;143(6):716. **PMID:** 17438178 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M17206 - Name: Ulcer - Relevance: LOW - As Found: Unknown - ID: M16070 - Name: Stomatitis - Relevance: HIGH - As Found: Stomatitis - ID: M16071 - Name: Stomatitis, Aphthous - Relevance: HIGH - As Found: Aphthous Stomatitis - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrent - ID: M21213 - Name: Oral Ulcer - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: T455 - Name: Aphthous Stomatitis - Relevance: HIGH - As Found: Aphthous Stomatitis ### Condition Browse Module - Meshes - ID: D000013280 - Term: Stomatitis - ID: D000013281 - Term: Stomatitis, Aphthous - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000010726 - Term: Phosphodiesterase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000010975 - Term: Platelet Aggregation Inhibitors - ID: D000011837 - Term: Radiation-Protective Agents - ID: D000020011 - Term: Protective Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000014665 - Term: Vasodilator Agents - ID: D000016166 - Term: Free Radical Scavengers - ID: D000000975 - Term: Antioxidants ### Intervention Browse Module - Browse Branches - Abbrev: VaDiAg - Name: Vasodilator Agents - Abbrev: PlAggInh - Name: Platelet Aggregation Inhibitors - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M13342 - Name: Pentoxifylline - Relevance: HIGH - As Found: Renal Function - ID: M13629 - Name: Phosphodiesterase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M13865 - Name: Platelet Aggregation Inhibitors - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown - ID: M14684 - Name: Radiation-Protective Agents - Relevance: LOW - As Found: Unknown - ID: M17412 - Name: Vasodilator Agents - Relevance: LOW - As Found: Unknown - ID: M4292 - Name: Antioxidants - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000010431 - Term: Pentoxifylline ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT00500279 **Acronym:** mini-COREA **Brief Title:** Effects of Celecoxib On Restenosis After Coronary Intervention and Evolution of Atherosclerosis Trial #### Organization Study ID Info **ID:** H-0611-011-188 #### Organization **Class:** OTHER **Full Name:** Seoul National University Hospital ### Status Module #### Completion Date **Date:** 2009-10 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2007-07-12 **Type:** ESTIMATED **Last Update Submit Date:** 2007-07-10 **Overall Status:** UNKNOWN #### Start Date **Date:** 2006-11 **Status Verified Date:** 2007-07 #### Study First Post Date **Date:** 2007-07-12 **Type:** ESTIMATED **Study First Submit Date:** 2007-07-10 **Study First Submit QC Date:** 2007-07-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Seoul National University Hospital ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** To evaluate the effect of celecoxib use for 3 month after drug-eluting stent implantation * on restenosis * on clinical outcome such as target lesion revascularization, thrombotic event, myocardial infarction, death * on inflammatory biomarkers **Detailed Description:** Restenosis is the major adverse effect of coronary stent implantation. Drug-eluting stent has markedly reduced restenosis as compared with bare-metal stent, but restenosis is still the main cause of repeat coronary intervention after drug-eluting stent implantation. After coronary stent implantation, inflammatory reaction occurs in vessel wall and vascular smooth muscle cells proliferate. Celecoxib is well known to have anti-proliferative effect as well as anti-inflammatory effect, and safety of this drug is well-established. Celecoxib use for 6 month after paclitaxel-eluting stent implantation significantly reduced neointimal growth and repeat intervention without increase in adverse effect. Because inflammatory reaction seems to occur in very early period after vessel injury, reduced use of celecoxib may also be effective. ### Conditions Module **Conditions:** - Angioplasty, Transluminal, Percutaneous Coronary - Coronary Restenosis **Keywords:** - Drug-eluting stent - Restenosis - Celecoxib ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 900 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Celecoxib **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** late luminal loss on quantitative coronary angiography **Time Frame:** six month #### Secondary Outcomes **Measure:** target lesion revascularization, myocardial infarction, death, thrombotic events **Time Frame:** six and eighteen month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * angina pectoris or a positive stress test with native coronary artery lesions feasible for drug-eluting stent implantation Exclusion Criteria: * acute or recent ST segment elevation myocardial infarction (within four weeks) * left main coronary artery disease * hepatic dysfunction (AST or ALT \> 120 IU/L ) * renal dysfunction (serum creatinine \> 2.0 mg/dl) * severe congestive heart failure (NYHA class \> 2) * left ventricular ejection fraction \< 30% * hemodynamically unstable condition * definite intracoronary thrombus * contraindication or history of allergy to aspirin, clopidogrel, or celecoxib * warfarin use * expected survival less than two years due to other medical conditions * patients already taking any COX-3 inhibitor or NASIDS **Maximum Age:** 75 Years **Minimum Age:** 30 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Hyosoo Kim, MD, PhD **Phone:** 82-2-2072-2226 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Jinwook Chung, MD **Phone:** 80-2-2072-3757 **Role:** CONTACT #### Locations **Location 1:** **City:** Seongnam **Country:** Korea, Republic of **Facility:** Seoul National University Bundang Hospital **Status:** RECRUITING **Zip:** 463-707 **Location 2:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Seuoul National University Hospital **Status:** RECRUITING **Zip:** 110-744 #### Overall Officials **Official 1:** **Affiliation:** Seoul National University Hospital **Name:** Hyosoo Kim, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Seoul National University Hospital **Name:** Bonkwon Koo, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Yang HM, Kim HS, Park KW, You HJ, Jeon SI, Youn SW, Kim SH, Oh BH, Lee MM, Park YB, Walsh K. Celecoxib, a cyclooxygenase-2 inhibitor, reduces neointimal hyperplasia through inhibition of Akt signaling. Circulation. 2004 Jul 20;110(3):301-8. doi: 10.1161/01.CIR.0000135467.43430.16. Epub 2004 Jul 6. **PMID:** 15238462 **Citation:** Wang K, Tarakji K, Zhou Z, Zhang M, Forudi F, Zhou X, Koki AT, Smith ME, Keller BT, Topol EJ, Lincoff AM, Penn MS. Celecoxib, a selective cyclooxygenase-2 inhibitor, decreases monocyte chemoattractant protein-1 expression and neointimal hyperplasia in the rabbit atherosclerotic balloon injury model. J Cardiovasc Pharmacol. 2005 Jan;45(1):61-7. doi: 10.1097/00005344-200501000-00011. **PMID:** 15613981 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000023921 - Term: Coronary Stenosis - ID: D000003327 - Term: Coronary Disease - ID: D000017202 - Term: Myocardial Ischemia - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000014652 - Term: Vascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M26188 - Name: Atherosclerosis - Relevance: LOW - As Found: Unknown - ID: M22912 - Name: Coronary Restenosis - Relevance: HIGH - As Found: Coronary Restenosis - ID: M6475 - Name: Constriction, Pathologic - Relevance: LOW - As Found: Unknown - ID: M22913 - Name: Coronary Stenosis - Relevance: LOW - As Found: Unknown - ID: M6549 - Name: Coronary Disease - Relevance: LOW - As Found: Unknown - ID: M6546 - Name: Coronary Artery Disease - Relevance: LOW - As Found: Unknown - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M19506 - Name: Myocardial Ischemia - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000023903 - Term: Coronary Restenosis ### Intervention Browse Module - Ancestors - ID: D000000894 - Term: Anti-Inflammatory Agents, Non-Steroidal - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000018501 - Term: Antirheumatic Agents - ID: D000052246 - Term: Cyclooxygenase 2 Inhibitors - ID: D000016861 - Term: Cyclooxygenase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Analg - Name: Analgesics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M277 - Name: Celecoxib - Relevance: HIGH - As Found: Air - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4218 - Name: Anti-Inflammatory Agents, Non-Steroidal - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M27009 - Name: Cyclooxygenase 2 Inhibitors - Relevance: LOW - As Found: Unknown - ID: M19209 - Name: Cyclooxygenase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068579 - Term: Celecoxib ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01925079 **Brief Title:** Intensive Education on Lipid Management **Official Title:** A Randomized and Controlled Study About the Impact of Intensive Education on Lipid Management in Patients With Acute Coronary Syndrome in China #### Organization Study ID Info **ID:** ACS-lipid-2013 #### Organization **Class:** OTHER **Full Name:** Shanghai Zhongshan Hospital ### Status Module #### Completion Date **Date:** 2015-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2013-08-20 **Type:** ESTIMATED **Last Update Submit Date:** 2013-08-18 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2015-02 **Type:** ESTIMATED #### Start Date **Date:** 2013-08 **Status Verified Date:** 2013-08 #### Study First Post Date **Date:** 2013-08-19 **Type:** ESTIMATED **Study First Submit Date:** 2013-08-15 **Study First Submit QC Date:** 2013-08-15 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Fujian Medical University **Class:** OTHER **Name:** The Second Affiliated Hospital of Harbin Medical University **Class:** OTHER **Name:** Health Science Center of Xi'an Jiaotong University **Class:** OTHER **Name:** The Luhe Teaching Hospital of the Capital Medical University #### Lead Sponsor **Class:** OTHER **Name:** Junbo Ge #### Responsible Party **Investigator Affiliation:** Shanghai Zhongshan Hospital **Investigator Full Name:** Junbo Ge **Investigator Title:** Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Among the patients with coronary heart disease, those with ACS (acute coronary syndrome) are extremely high-risk patients. Therefore, management outside hospital, especially the regular administration of drugs, is vital to prevent the recurrence of cardiovascular events. However, most patients often fail to stay on a long-term administration regimen, especially the administration of statins. According to the statistics, the average duration adhered with statin in patients with ACS is less than 3 months, use of statin at hospital discharge was only 80% and 65% in 6 month, with a very low LDL-C control rate (about 11% at 6 months), which poses a threat to the recurrence rate of cardiovascular events in patients with ACS. It was found in previous studies that there were many factors influencing patients' compliance, in which patients' refusing to take medicine accounted for a higher proportion. It suggests that patient had not recognized the importance of long-term administration. Therefore, it is extremely important for physicians to strengthen patient education and regular follow-up visits during disease management. Moreover, the effectiveness of patient education during chronic disease management has already been proved in some studies abroad, and the interventional effect of multiple patient education process outweighs that of single approach education. Thus, we intend to conduct a randomized and controlled study to explore the effect of multi-channel intensive patient education on LDL-C target achieving rate and statin adherence in patients with ACS in China. ### Conditions Module **Conditions:** - Acute Coronary Syndrome **Keywords:** - acute coronary syndrome - statins - LDL-C - intensive education ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 2568 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The Intensive Educational Group will receive 5 visits, including 2 visits via phone contacts. The expected dates for each visit will be stamped on the follow-up brochure for convenience. Patient education in this group includes routine education at discharge; 4 educational brochures, a calendar with health tips, and follow-up brochure with medical expert letter sent to patients at the day for discharge (baseline); and educational short messages through message platform once a week. Dosage and adjustment of statins, and concomitant medications in all the treated patients will be recorded. **Intervention Names:** - Behavioral: Intensive Education **Label:** Intensive Educational Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The Control Group will receive 3 visits and receive care as per usual practice by the treating doctor and a follow-up brochure without medical expert letter. Dosage and adjustment of statins, and concomitant medications in all the treated patients will be recorded. Blood lipid panel (4 items), hepato-renal functions, and creatine kinase will be examined; while, Morisky 8-item questionnaire will be used to evaluate medication compliance at outpatient visits. In addition, the occurrence of major cardiovascular events and AE/SAE will be collected during the study. **Intervention Names:** - Other: Control **Label:** Control Group **Type:** SHAM_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intensive Educational Group **Description:** Statin Treatment：The investigator will be suggested to increase the dose of atorvastatin according to guideline if a patient's LDL-C does not achieve target level. Patient education: 1. Routine education at discharge. 2. 4 education brochures will be delivered to patients. 3. Calendar with healthy tips will be delivered to patients before discharge. 4. A follow-up brochure with medical expert letter. 5. A total of 24 specific short messages for ACS will be developed and sent to patients (one short message per week). 6. Telephone follow ups will be performed according to a standard communication document. At discharge, patients will be given a brochure for future follow up. **Name:** Intensive Education **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Control Group **Description:** Statin Treatment：The recommended dosage of atorvastatin will be adjusted at the physician's discretion. Patient education: 1. Routine education at discharge. 2. A follow-up brochure without medical expert letter. At discharge, patients will be given a brochure for future follow up. **Name:** Control **Type:** OTHER ### Outcomes Module #### Other Outcomes **Measure:** the major adverse cardiovascular events **Time Frame:** at 24 weeks follow up #### Primary Outcomes **Measure:** LDL-C target achieving rate **Time Frame:** at Week 24 post-discharge #### Secondary Outcomes **Measure:** LDL-C target achieving rate **Time Frame:** at Week 12 post-discharge **Measure:** the proportions of patients with statin persistence **Time Frame:** at Week 12 post-discharge **Measure:** the proportions of patients with statin persistence **Time Frame:** at Week 24 post-discharge **Measure:** statin compliance **Time Frame:** at Week 12 post-discharge **Measure:** statin compliance **Time Frame:** at Week 24 post-discharge **Measure:** the relationship of LDL-C target achieving rate and statin compliance **Time Frame:** at Week 24 post-discharge **Measure:** the discontinuation reason of statin therapy **Time Frame:** at Week 24 post-discharge **Description:** To find the difference of LDL-C control rate and statin compliance between pre-specified sub-groups: PCI or non-PCI/male or female/age (≥65) or not/ having medical insurance or not/dyslipidemia history or not /MI (myocardial infarction) or UA (unstable angina)/different risk level according to TIMI/ patients for first consulting or patients with recurrence/ have received statin in the last 3 months or not. **Measure:** the difference of LDL-C control rate and statin compliance **Time Frame:** at Week 24 post-discharge ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. The patients admitted to the hospital with a diagnosis of ACS including those for first consulting or with recurrence. The patient was prescribed atorvastatin (Lipitor®) by physicians in hospital; 2. The age of patient enrolled will be ≥18 years old; 3. The patient is able to understand and complete questionnaire. 4. The patients agree to accept follow-up visits, and willing to participate in patient education courses and sign informed consent form. Exclusion Criteria: 1. The patient has contraindications to statins, such as active hepatic disease, patient has a history of intolerance or hypersensitivity to statins or has a history of prior rhabdomyolysis on a statin. 2. The patient who uses other statins except Lipitor® when discharged from the hospital; 3. Cardiac function class of the patient is class IV(NYHA); 4. The patient has a malignant tumor; 5. The patient has a severe arrhythmia. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Bingqing Huang **Phone:** 86-13816586495 **Role:** CONTACT #### Locations **Location 1:** **City:** Fuzhou **Contacts:** ***Contact 1:*** - **Name:** Ziliang Chen, Professor - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Fujian Medical University Union Hospital **State:** Fujian **Location 2:** **City:** Harbin **Contacts:** ***Contact 1:*** - **Name:** Bo Yu, Professor - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** The 2nd affiliated hospital of harbin medical university **State:** Heilongjiang **Zip:** 150001 **Location 3:** **City:** Xi'an **Contacts:** ***Contact 1:*** - **Name:** Zhuyi Yuan, Professor - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Xi'an Jiaotong University College of Medicine **State:** Shanxi **Zip:** 710061 **Location 4:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Name:** Jincheng Guo, Professor - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** The Luhe Teaching Hospital of the Capital Medical University **Location 5:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Name:** Junbo Ge, Professor - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Shanghai Zhongshan Hospital **Zip:** 200032 #### Overall Officials **Official 1:** **Affiliation:** Fudan University **Name:** Junbo Ge, Professor **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000017202 - Term: Myocardial Ischemia - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000014652 - Term: Vascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M27545 - Name: Acute Coronary Syndrome - Relevance: HIGH - As Found: Acute Coronary Syndrome - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M6546 - Name: Coronary Artery Disease - Relevance: LOW - As Found: Unknown - ID: M19506 - Name: Myocardial Ischemia - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000054058 - Term: Acute Coronary Syndrome - ID: D000013577 - Term: Syndrome ### Intervention Browse Module - Browse Branches - Abbrev: Lipd - Name: Lipid Regulating Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M351 - Name: Atorvastatin - Relevance: LOW - As Found: Unknown - ID: M21155 - Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors - Relevance: LOW - As Found: Unknown - ID: T385 - Name: Creatine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02099279 **Brief Title:** Prognostic Value Cardiac Dysfunction Assessed by Bedside Echocardiography in Critically Ill COPD Patients Requiring Mechanical Ventilation #### Organization Study ID Info **ID:** echo_COPD #### Organization **Class:** OTHER **Full Name:** Jinhua Central Hospital #### Secondary ID Infos **Domain:** echo and COPD **ID:** echo and COPD **Type:** REGISTRY ### Status Module #### Completion Date **Date:** 2015-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-09-01 **Type:** ESTIMATED **Last Update Submit Date:** 2015-08-31 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-01 **Type:** ACTUAL #### Start Date **Date:** 2014-01 **Status Verified Date:** 2014-03 #### Study First Post Date **Date:** 2014-03-28 **Type:** ESTIMATED **Study First Submit Date:** 2014-03-23 **Study First Submit QC Date:** 2014-03-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Jinhua Central Hospital #### Responsible Party **Investigator Affiliation:** Jinhua Central Hospital **Investigator Full Name:** Zhongheng Zhang **Investigator Title:** intensivist **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Chronic obstructive lung disease (COPD) is a major cause of morbidity and mortality, and is a major reason for ICU admission. Cardiac function is often impaired in this disease but its association with clinical outcome has not been fully established. The study aims to investigate the association between cardiac dysfunction and clinclial outcomes. **Detailed Description:** This is a prospective observational study conducted in a 47-bed mixed ICU of tertiary academic teaching hospital. The study will be performed between January 2014 to December 2015. All patients meeting the diagnostic criteria of AECOPD and admitted to ICU are potentially eligible for the present study. Relevant demographics and laboratory measurements are obtained. Transthoracic echocardiography (TTE) is performed immediately after ICU admission by experienced intensivists. Cox proportional hazard regression model is fitted by using stepwise forward selection and backward elimination technique. If linear assumption is not satisfied, the linear spline function will be used. ### Conditions Module **Conditions:** - COPD Patients - Mechanical Ventilation ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 53 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Device: echocardiography examination **Label:** echocardiography examination ### Interventions #### Intervention 1 **Arm Group Labels:** - echocardiography examination **Description:** patients underwent echocardiography examination **Name:** echocardiography examination **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** 28 days after ICU admission; if a patient leave ICU before 28-days, it is considered as censored. **Measure:** 28-day mortality **Time Frame:** 28 days after ICU admission #### Secondary Outcomes **Measure:** duration of mechanical ventilation **Time Frame:** from ICU admission to extubation, an expected average of 8 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * COPD patients experiencing episode of exacerbation and require mechanical ventilation were admitted to ICU Exclusion Criteria: * COPD patients admitted to ICU due to other reasons (major surgery, ischemic heart disease, and renal failure) * moribund and expected to die within 48 hours * with Do-Not-Resuscitation order **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** All patients meeting the diagnostic criteria of AECOPD and admitted to ICU are potentially eligible for the present study. The diagnosis of AECOPD is based on that defined in Global Initiative for Chronic Obstructive Pulmonary Disease. AECOPD is defined using definitive criteria with at least two of the following major symptoms: increased dyspnea, increased sputum purulence, increased sputum volume; or one major and one minor symptom: nasal discharge/congestion, wheeze, sore throat and cough for at least two consecutive days. ### Contacts Locations Module #### Locations **Location 1:** **City:** Jinhua **Country:** China **Facility:** Jinhua municipal central hospital **State:** Zhejiang **Zip:** 321000 #### Overall Officials **Official 1:** **Affiliation:** Jinhua Municipal Central Hospital **Name:** Chen Kun, MB **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Zhang Z, Chen L, Chen K, Ni H. The prognostic value of cardiac dysfunction assessed by bedside echocardiography in critically ill patients with COPD requiring mechanical ventilation: a study protocol. BMJ Open. 2014 Sep 25;4(9):e005359. doi: 10.1136/bmjopen-2014-005359. **PMID:** 25256186 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M19010 - Name: Critical Illness - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02809079 **Acronym:** MONICA **Brief Title:** Mycophenolate Mofetil Treatment With Neuromyelitis Optica Spectrum Disorders in Chinese Patients **Official Title:** Mycophenolate Mofetil Treatment With Neuromyelitis Optica Spectrum Disorders in Chinese Patients #### Organization Study ID Info **ID:** 2016017 #### Organization **Class:** OTHER **Full Name:** Third Affiliated Hospital, Sun Yat-Sen University ### Status Module #### Completion Date **Date:** 2017-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ENROLLING_BY_INVITATION #### Last Update Post Date **Date:** 2016-06-22 **Type:** ESTIMATED **Last Update Submit Date:** 2016-06-19 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2017-12 **Type:** ESTIMATED #### Start Date **Date:** 2016-01 **Status Verified Date:** 2016-06 #### Study First Post Date **Date:** 2016-06-22 **Type:** ESTIMATED **Study First Submit Date:** 2016-06-12 **Study First Submit QC Date:** 2016-06-19 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Zhongshan Ophthalmic Center, Sun Yat-sen University **Class:** OTHER **Name:** Southern Medical University, China #### Lead Sponsor **Class:** OTHER **Name:** Third Affiliated Hospital, Sun Yat-Sen University #### Responsible Party **Investigator Affiliation:** Third Affiliated Hospital, Sun Yat-Sen University **Investigator Full Name:** Wei Qiu **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Neuromyelitis optica (NMO) is an autoimmune inflammatory demyelinating disease of the central nervous system that leads to blindness and paralysis. Since disability accrues incrementally related to attacks, attack prevention with immunosuppressive therapy is the mainstay of preventing disability. However, there is no standard immunosuppressive treatment strategy for NMO relapse prevention. In a previous study, the investigators provided evidence supporting the use of azathioprine plus a low dose corticosteroid as an effective strategy which is associated with a reduction in the risk of relapse in Chinese patients with NMO, but azathioprine has bone marrow suppression and other side effects. Mycophenolate mofetil (MMF) is a new immunosuppressant with rapid onset, fewer side effects and other advantages. In recent years, MMF has been used in different immune-related neurological diseases; some literature shown the possible efficacy of MMF in NMO treatment. In this research, a multi-center (Third Affiliated Hospital of Sun Yat-sen University, Zhongshan Ophthalmic Centre of Sun Yat-sen University, Nangfang Hospital of Southern Medical University) study will carry out to evaluate the efficacy and safety of mycophenolate mofetil therapy in NMO spectrum disorders. ### Conditions Module **Conditions:** - Neuromyelitis Optica Spectrum Disorders - Mycophenolate Mofetil - Efficacy and Safety ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Mycophenolate mofetil 500mg Bid and prednisone 10mg Qd **Intervention Names:** - Drug: Mycophenolate mofetil - Drug: Prednisone **Label:** Mycophenolate mofetil plus prednisone **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Mycophenolate mofetil plus prednisone **Description:** Mycophenolate mofetil 500mg Bid **Name:** Mycophenolate mofetil **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Mycophenolate mofetil plus prednisone **Description:** prednisone 10mg Qd **Name:** Prednisone **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Patients come back for follow-up visit on day 360 after staring treatment, and annualized relapse rate was evaluated. **Measure:** Annualized relapse rate day 360 **Time Frame:** day 360 after staring treatment #### Secondary Outcomes **Description:** Patients come back for follow-up visit on day 1, 14, 30, 90, 180, 270, 360 after staring treatment, and expanded disability status scale was evaluated. **Measure:** expanded disability status scale **Time Frame:** day 1, 14, 30, 90, 180, 270, 360 after staring treatment **Description:** Patients come back for follow-up visit on day 1, 14, 30, 90, 180, 270, 360 after staring treatment, and Hauser scale was evaluated. **Measure:** Hauser scale **Time Frame:** day 1, 14, 30, 90, 180, 270, 360 after staring treatment **Description:** Patients come back for follow-up visit on day 1, 14, 30, 90, 180, 270, 360 after staring treatment, and vision scale was evaluated. **Measure:** vision scale **Time Frame:** day 1, 14, 30, 90, 180, 270, 360 after staring treatment **Description:** Patients come back for follow-up visit on day 1, 14, 30, 90, 180, 270, 360 after staring treatment, lesions in brain and spinal cord were evaluated by MRI. **Measure:** Lesions in brain and spinal cord **Time Frame:** day 1, 14, 30, 90, 180, 270, 360 after staring treatment **Description:** Patients come back for follow-up visit on day 1, 14, 30, 90, 180, 270 after staring treatment, and annualized relapse rate was evaluated. **Measure:** Annualized relapse rate **Time Frame:** day 1, 14, 30, 90, 180, 270 after staring treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Meet the 2006 Wingerchuk diagnostic criteria; * NMO-immunoglobulin G seropositive; * Between 18 to 65 years old; * Relapse: more than 2 relapses in recent 2 years; more than 1 relapses in recent 1 years; * Expanded disability status scale: expanded disability status scale≤7.0, and visual acuity ≥20 / 100 at least in one eye * Understand the purpose and procedures of this study, and written informed consent is obtained. Exclusion Criteria: * Using immunosuppressive agents and other drugs affect evaluation, and drug withdrawal less than 3 months; * Patients with any of the following diseases: transaminases elevation exceed 2 times of the normal upper limit; white blood cell \<4 × 109 / L, Hemoglobin \<80g / L, platelet \<100 × 109 / L; * With serious cardiovascular, liver, kidneys and other vital organs and blood, endocrine system diseases, cancer history; * With immunodeficiency, uncontrolled infection and active gastrointestinal diseases (such as gastric ulcer, etc.); * Pregnancy, breast-feeding women and male or female who plans to conceive recently; * Allergy to mycophenolate mofetil and prednisone. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Third Affiliated Hospital, Sun Yat-Sen University **Name:** Wei Qiu, Medical PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** share by publications and meetings **IPD Sharing:** YES ### References Module #### References **Citation:** Falcini F, Trapani S, Ricci L, Resti M, Simonini G, de Martino M. Sustained improvement of a girl affected with Devic's disease over 2 years of mycophenolate mofetil treatment. Rheumatology (Oxford). 2006 Jul;45(7):913-5. doi: 10.1093/rheumatology/kei263. Epub 2006 Apr 25. No abstract available. **PMID:** 16638802 **Citation:** Huh SY, Kim SH, Hyun JW, Joung AR, Park MS, Kim BJ, Kim HJ. Mycophenolate mofetil in the treatment of neuromyelitis optica spectrum disorder. JAMA Neurol. 2014 Nov;71(11):1372-8. doi: 10.1001/jamaneurol.2014.2057. **PMID:** 25199960 **Citation:** Jacob A, Matiello M, Weinshenker BG, Wingerchuk DM, Lucchinetti C, Shuster E, Carter J, Keegan BM, Kantarci OH, Pittock SJ. Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol. 2009 Sep;66(9):1128-33. doi: 10.1001/archneurol.2009.175. **PMID:** 19752302 **Citation:** Huang Q, Wang J, Zhou Y, Yang H, Wang Z, Yan Z, Long Y, Yin J, Feng H, Li C, Lu Z, Hu X, Qiu W. Low-Dose Mycophenolate Mofetil for Treatment of Neuromyelitis Optica Spectrum Disorders: A Prospective Multicenter Study in South China. Front Immunol. 2018 Sep 11;9:2066. doi: 10.3389/fimmu.2018.02066. eCollection 2018. **PMID:** 30258442 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009188 - Term: Myelitis, Transverse - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000009902 - Term: Optic Neuritis - ID: D000009901 - Term: Optic Nerve Diseases - ID: D000003389 - Term: Cranial Nerve Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000005128 - Term: Eye Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC11 - Name: Eye Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC04 - Name: Neoplasms - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12414 - Name: Neuromyelitis Optica - Relevance: HIGH - As Found: Neuromyelitis Optica - ID: M12142 - Name: Myelitis - Relevance: LOW - As Found: Unknown - ID: M12143 - Name: Myelitis, Transverse - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M12387 - Name: Neuritis - Relevance: LOW - As Found: Unknown - ID: M12833 - Name: Optic Neuritis - Relevance: LOW - As Found: Unknown - ID: M12832 - Name: Optic Nerve Diseases - Relevance: LOW - As Found: Unknown - ID: M6605 - Name: Cranial Nerve Diseases - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T4103 - Name: Neuromyelitis Optica Spectrum Disorder - Relevance: HIGH - As Found: Neuromyelitis Optica Spectrum Disorder - ID: T3988 - Name: Myelitis - Relevance: LOW - As Found: Unknown - ID: T4263 - Name: Optic Neuritis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009471 - Term: Neuromyelitis Optica ### Intervention Browse Module - Ancestors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018931 - Term: Antineoplastic Agents, Hormonal - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000903 - Term: Antibiotics, Antineoplastic - ID: D000000904 - Term: Antibiotics, Antitubercular - ID: D000000995 - Term: Antitubercular Agents - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M14121 - Name: Prednisone - Relevance: HIGH - As Found: Min - ID: M12128 - Name: Mycophenolic Acid - Relevance: HIGH - As Found: Mindfulness - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M4311 - Name: Antitubercular Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000009173 - Term: Mycophenolic Acid - ID: D000011241 - Term: Prednisone ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04721379 **Brief Title:** Effect of Heartfulness Meditation on Brain Waves and How Calm One Feels During Meditation **Official Title:** Impact of Heartfulness Meditation on EEG (Brain Waves) and Meditation Depth #### Organization Study ID Info **ID:** 1654972 #### Organization **Class:** OTHER **Full Name:** WellSpan Health ### Status Module #### Completion Date **Date:** 2023-02-15 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-10-11 **Type:** ACTUAL **Last Update Submit Date:** 2021-10-06 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-08-15 **Type:** ESTIMATED #### Start Date **Date:** 2021-07-31 **Type:** ACTUAL **Status Verified Date:** 2021-10 #### Study First Post Date **Date:** 2021-01-22 **Type:** ACTUAL **Study First Submit Date:** 2021-01-06 **Study First Submit QC Date:** 2021-01-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** WellSpan Health #### Responsible Party **Investigator Affiliation:** WellSpan Health **Investigator Full Name:** Jay Thimmapuram **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Objectives: 1. To assess the EEG patterns and EKG recordings of participants with no meditation experience with simply closing the eyes for 10 minutes followed by relaxing for 30 minutes. 2. To assess the EEG patterns and EKG recordings of participants with no meditation experience by simply closing the eyes for 10 minutes and then with guided Heartfulness relaxation and meditation for 30 minutes. 3. To assess the baseline anxiety score through GAD-7 questionnaire, subjective experience of all the participants through MEDEQ questionnaire that measures the depth of the meditation experience after the session and correlate with the EEG patterns of the brain and heart rate changes. EEG and EKG data from the groups will be analyzed by the sleep specialist. EKG device data for HRV and the EEG data will be correlated with the subjective depth of meditation experience in both the groups **Detailed Description:** Neurological correlates of states of mind during meditation have been studied with Electroencephalogram (EEG) and functional MRIs for many decades. Meditation practices produce distinct EEG brain waveforms, and this may be reflective of the overall subjective experiences. Long term meditators using mindfulness have shown gamma activation on EEG recordings. Practice of Yoganidra and Sahaja meditation have been reported to show increased theta activity. Transcendental Meditation practices have shown alpha waves during meditative periods. While most of the meditative practices may appear similar, there may be subtle differences that might make them better suited for particular conditions. However, most of the studies conducted were small, non-randomized and therefore the outcomes are unclear. The investigators wish to conduct a randomized controlled prospective study using Heartfulness meditation techniques. Heartfulness meditation practice is a simple heart-based meditation practice that has been shown to improve burnout, emotional wellness and sleep. In a younger subset of patients, it has also shown to increase the telomere length. However, the neurological and physiological correlates of this practice have not been assessed. This study will investigate whether using this novel approach of a heart-based meditation program leads to measurable changes in the EEG and also whether there is any correlation with the waveforms and the depth of meditation. This may provide an explanation from a neurological basis for the improvement of certain wellness parameters such as sleep. In addition, meditation practices have been shown to have positive benefits on cardiovascular system including heart rate variability (HRV). Cardiovascular physiology measured by continuous electrocardiogram (EKG) monitoring is a non-invasive way of measuring HRV. In this study, a correlation of the EEG and HRV with the subjective depth of meditation experience measured through meditation depth questionnaire (MEDEQ) along with baseline anxiety score as measured by generalized anxiety disorder scale (GAD-7) will be assessed. Primary outcome and Hypotheses: 1. The primary outcome will be observing a change in EEG pattern of subjects who follow a Heartfulness guided meditation as compared to unguided self-relaxation and meditation. 2. The study team hypothesize that guided Heartfulness meditation will be associated with deeper relaxed brain wave patterns - predominantly theta and delta waves - compared to beta and alpha waves in unguided self-relaxation and meditation. The investigators anticipate that subjects will perceive an increased depth of meditation during a guided relaxation session compared to simply closing the eyes for the duration of the study. Since participants have no prior meditation experience, the investigators hypothesize that the first attempt at meditation is adequate to induce a relaxed state and EEG changes. 3. With regards to EKG changes, the study team hypothesize that there will be a reduction in heart rate and increased beat-to-beat variability with guided meditation as compared to unguided self-relaxation for the same duration. ### Conditions Module **Conditions:** - Anxiety - Stress **Keywords:** - meditation - Heartfulness - EEG - Heart rate ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Participants will be randomized into two groups. 1. Group 1 participants with unguided session simply close their eyes for 10 minutes while EEG and EKG recordings are performed. Following 10 minutes, after briefly opening their eyes, they will be asked to relax with eyes closed for 30 minutes. After finishing the session, they fill out meditation depth questionnaire. 2. Group 2 participants with guided sessions close their eyes for 10 minutes while EEG and EKG recordings are performed. Following 10 minutes, after briefly opening their eyes, they will be guided through relaxation and meditation session for 30 minutes with a Heartfulness trainer with continued recording. After finishing the session, they also fill out meditation depth questionnaire. ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 80 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will be guided through relaxation and meditation session with a Heartfulness trainer with EEG and EKG recording. After finishing the session, they fill out meditation depth questionnaire. **Intervention Names:** - Behavioral: Meditation **Label:** Heartfulness Meditation Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will be self-guided through relaxation and meditation session without a trainer with EEG and EKG recording. After finishing the session, they fill out meditation depth questionnaire. **Intervention Names:** - Behavioral: Meditation **Label:** Control Group with Self Meditation **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Control Group with Self Meditation - Heartfulness Meditation Group **Description:** 1. Group 1 participants with unguided session simply close their eyes for 10 minutes while EEG and EKG recordings are performed. Following 10 minutes, after briefly opening their eyes, they will be asked to relax with eyes closed for 30 minutes. After finishing the session, they fill out meditation depth questionnaire. 2. Group 2 participants with guided sessions close their eyes for 10 minutes while EEG and EKG recordings are performed. Following 10 minutes, after briefly opening their eyes, they will be guided through relaxation and meditation session for 30 minutes with a Heartfulness trainer with continued recording. After finishing the session, they also fill out meditation depth questionnaire. **Name:** Meditation **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** During meditation, EEG will be recorded using brain wave leads. **Measure:** Brain wave changes with Heartfulness guided meditation comparing with self-guided meditation **Time Frame:** Through completion of study, average of one hour. **Description:** During meditation, EKG will be recorded using chest leads. **Measure:** EKG changes with Heartfulness guided meditation comparing with self-guided meditation **Time Frame:** Through completion of study, average of one hour. **Description:** The questionnaire will be completed after the 10 minute meditation session and again after 30 minute meditation session **Measure:** Meditation depth Index questionnaire with Heartfulness guided meditation comparing with self-guided meditation **Time Frame:** After the meditation session, average of 10 minutes #### Secondary Outcomes **Description:** Using Generalized Anxiety Disorder -7 score. Scores 5-9 indicate mild anxiety, 10-14 indicate moderate anxiety and 15-21 indicate severe anxiety. **Measure:** Generalized Anxiety score **Time Frame:** Before the meditation session, average of 5 minutes. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: • Adults above 18 years of age willing to participate in the study. Exclusion Criteria: * Participants unwilling to participate in the study and those with prior meditation experience. * Participants who are unable to sit for 30 minutes due to either physical or mental conditions will be excluded. * Participants with bipolar disorder, substance abuse (drugs or alcohol abuse in last 6 months), alcohol withdrawal, BMI \< 18, suicidal ideation, active psychotherapy, major depression, anxiety disorder, obstructive sleep apnea, eating disorder, history of brain surgery or known brain tumors, known seizures or on treatment for seizures, borderline personality disorder, post-traumatic stress disorder, or psychotic disorder. * Participants with known heart rhythm problems such as atrial fibrillation is advised not to participate. * Participants on benzodiazepines or psychiatry medications, stimulants or sleeping pills that may potentially interfere with EEG patterns will be excluded. * Participants on cardiovascular medications that affect the heart rate will be excluded. * Participants who are unable to have the leads on their scalp or skin will be excluded. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Jayaram Thimmapuram, MD **Phone:** 717-851-2223 **Role:** CONTACT #### Locations **Location 1:** **City:** Dover **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Jayaram Thimmapuram - **Phone:** 717-495-6027 - **Role:** CONTACT **Country:** United States **Facility:** WellSpan Dover Sleep Center **State:** Pennsylvania **Status:** RECRUITING **Zip:** 17315 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04774679 **Brief Title:** Macroscopic on Cite Evaluation of EUS-FNA Specimen With 22 G Needle **Official Title:** Macroscopic on Cite Evaluation of EUS-FNA Specimen of Gastrointestinal Tumours With Everyday Needle (22g EUS FNA Needle) #### Organization Study ID Info **ID:** MOSE #### Organization **Class:** OTHER **Full Name:** Kocaeli University ### Status Module #### Completion Date **Date:** 2021-03-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-03-01 **Type:** ACTUAL **Last Update Submit Date:** 2021-02-24 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-03-15 **Type:** ESTIMATED #### Start Date **Date:** 2021-02-06 **Type:** ACTUAL **Status Verified Date:** 2021-02 #### Study First Post Date **Date:** 2021-03-01 **Type:** ACTUAL **Study First Submit Date:** 2021-02-06 **Study First Submit QC Date:** 2021-02-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Kocaeli University #### Responsible Party **Investigator Affiliation:** Kocaeli University **Investigator Full Name:** Hasan Yılmaz **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** In order for the diagnosis of digestive system tumors and their appropriate treatment afterward, the type of these tumors should be determined by the pathologist. Pathology doctors need sufficient tissue (a small part of the organ thought to be diseased) to make a diagnosis. Tissue samples were taken from the patients by biopsy procedure. It is examined with microscopes by performing various staining and occasionally it is reported that sufficient tissue cannot be provided to make a diagnosis. In this case, patients may be subjected to repeated biopsy procedures. The aim of this study is to investigate whether the biopsy material obtained by endoscopic ultrasonography (EUS) is sufficient for the diagnosis of the pathology physician with the naked eye. Researchers will try to determine to what extent the physician performing the biopsy procedure can predict whether the tissue he has obtained is sufficient for the pathologist. In this way, researchers think that fewer biopsy repetitions will be needed in the future. **Detailed Description:** This study was designed to improve the acquisition of sufficient tissue (EUS-FNA) with endosonography-assisted fine needle aspiration biopsy, which has been approved and used worldwide for the diagnosis of digestive system diseases. The procedure to be applied in the study is to determine the visible tissue fragments in the sample to be taken after the standard EUS-FNA procedure and to compare it with the diagnosis made by the pathologist. Patients with a tumor detected in the digestive system and referred to the investigation unit for tissue diagnosis will be included in this study. The data obtained in the study will be collected prospectively and will be analyzed retrospectively. ### Conditions Module **Conditions:** - GI Cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All patients who underwent EUS Guided biopsy **Intervention Names:** - Procedure: Endosonographic fine needle aspiration biopsy **Label:** Biopsy Arm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Biopsy Arm **Description:** An endoscopic ultrasound device will be inserted to the stomach and biopsy will performed with a needle **Name:** Endosonographic fine needle aspiration biopsy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Macroscopic appearance of the tissue fragments obtained by 22G EUS-FNA needle will be assessed by the endoscopist immediately in the endoscopy room. Endoscopits will decide the tissue acquisition is adequate. The diagnostic yield of the specimens determined by a pathologist will be compared to the endoscopist's first decision according to the macroscopic appearance. **Measure:** Correlation of a macroscopically visible fragments in the 22g EUS-FNA needle specimens with final histologic diagnosis **Time Frame:** 1-2 weeks #### Secondary Outcomes **Description:** Macroscopically visiable core size obtained via 22G EUS -FNA needle and pathologic size of cores will be compared by using **Measure:** Area Under the size of the macroscopically visible core size versus histologic core size **Time Frame:** 1-2 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. İn the age range of 18-80 years old 2. Tumour detected withcross-sectional imagined technics in the digestive system Exclusion Criteria: 1. Refuse to give written informed consent 2. Established bleeding disorder 3. INR\>1.5IU plaelet count \<100000/dL **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Hasan Yılmaz **Phone:** +905058774821 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Ali Erkan Duman **Phone:** +905335640607 **Role:** CONTACT #### Locations **Location 1:** **City:** Izmit **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Hasan Yılmaz, MD - **Phone:** +905058774821 - **Role:** CONTACT **Country:** Turkey **Facility:** Kocaeli University Medical Faculty Hospital **State:** Kocaeli **Status:** RECRUITING **Zip:** 41001 ### IPD Sharing Statement Module **Access Criteria:** publicly **Description:** Data will be shared at Mendeley data sharing platform freely and publicly **Info Types:** - STUDY_PROTOCOL - CSR - ANALYTIC_CODE **IPD Sharing:** YES **Time Frame:** 1 month after the study compilation ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT06212479 **Acronym:** Hercules **Brief Title:** An Observational Study On TheAccuracy Of Whole-Body Magnetic Resonance Imaging (Wb-Mri) ScreeningTo Predict Clinically Significant Diagnoses In General Population Subjects Interested In Proactive And Advanced General Preventive Healthcare. **Official Title:** A Multi-Site Prospective, Single-Arm, Observational Study On The Accuracy Of Whole Body Magnetic Resonance Imaging (Wb-Mri) Screening To Predict Clinically Significant Diagnoses In General Population Subjects Interested In Proactive And Advanced General Preventive Healthcare. #### Organization Study ID Info **ID:** MA- 001 #### Organization **Class:** INDUSTRY **Full Name:** Hercules ### Status Module #### Completion Date **Date:** 2037-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ESTIMATED **Last Update Submit Date:** 2024-05-23 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2034-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-17 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-01-18 **Type:** ACTUAL **Study First Submit Date:** 2023-12-26 **Study First Submit QC Date:** 2024-01-08 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Prenuvo Inc #### Lead Sponsor **Class:** INDUSTRY **Name:** Hercules #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This is a prospective, single-arm, observational study capturing data from whole-body magnetic resonance imagining (WB-MRI) from up to 100,000 male and female subjects 18 years of age or older recruited at multiple clinical sites within the United States. Study subjects must meet a set of inclusion and exclusion criteria. Potential subjects arriving at the study sites will be evaluated for enrollment. It is the Principal Investigator's (PI) responsibility to enroll only subjects who satisfy the inclusion/exclusion criteria. Recruitment can occur by subject presentation at the sites for elective standard screening, word-of-mouth, flyers, healthcare professional (HCP) referrals, advertisement online, or any other means, subject to approval by the associated institutional review board (IRB) or ethics committee (EC) when applicable. ### Conditions Module **Conditions:** - Cancer - Metabolic Disease - Aneurysm - Neurologic Disorder ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 100000 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Whole Body MRI Scan **Intervention Names:** - Diagnostic Test: MRI Scan **Label:** MRI Scan Arm ### Interventions #### Intervention 1 **Arm Group Labels:** - MRI Scan Arm **Description:** Whole Body MRI Scan **Name:** MRI Scan **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Clinically significant disease represents the primary output of WB-MRI image analysis, and thus, the primary endpoint for this study. This outcome will be expressed as a 5-point scale similar to the standard Likert scale used in clinical studies. Higher the number higher the risk of clinically significant finding. **Measure:** Primary Endpoint and 5-point scale of CSD (Clinically Significant Disease) of CSD diagnosed post-baseline in general population subjects. **Time Frame:** Up to 10 Years #### Secondary Outcomes **Description:** Additionally, for the purposes of more specifically distinguishing CSD's of oncological-concern, following the ONCO-RADS7 guidelines for cancer screening utilizing WB-MRI, an additional ONCO-RADS score tag ("ONCO") will be attached to each CSD to reflect oncologic-specific risk according to the screening WB-MRI criteria. Higher the number worse the risk of having Cancer. **Measure:** Secondary Endpoint of ONCO-RADS Score (Oncological relevant findings reporting and data system) diagnosed in the follow-up period, including but not limited to, types of cancers, aneurysms, metabolic disorders, neurologic disorders, renal function, etc **Time Frame:** Up to 10 Years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Each subject MUST: * Be\>=18 years of age at the time of enrollment. * Be able to read and understand provided procedural information for the study; * Be able and willing to follow all study procedures including proper breathing and body movement minimization while within the WB-MRI system; * Be willing and able to provide required clinical, demographic, medical history, and concomitant medications information; * Be able to provide financial payment in advance for reimbursement of the cost of the WBMRI acquisition procedure and interpretation; * Complete all required consent procedures. Exclusion Criteria: * Harbor within their bodies contraindicated medical devices including, but not limited to, implanted pacemakers, intracranial aneurysm clips, cochlear implants, drug infusion pumps, neurostimulators, bone growth stimulators, certain intrauterine contraceptive devices, non- MRI safe metals, etc.; * Self-certify that they are pregnant; * Be seeking to undergo WB-MRI as a subject in this study in lieu of other covered dedicated diagnostic imaging evaluations when such covered procedures represent more appropriate or standard-of-care procedures by context-specific clinical indication; * Be an employee of the study site or the sponsor; * Have a medical condition or serious intercurrent illness, or other circumstance that, in the Investigator's judgment, could jeopardize the candidate's safety as a study subject, or that could interfere with study objectives. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** All the patients above 18 years of age. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Pratik Shingru, MD, MPH **Phone:** 8337736886 **Role:** CONTACT #### Locations **Location 1:** **City:** Watertown **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Pratik Shingru, MD - **Role:** CONTACT **Country:** United States **Facility:** Hercules Research Center **State:** Massachusetts **Status:** RECRUITING **Zip:** 02472 #### Overall Officials **Official 1:** **Affiliation:** Hercules **Name:** Perry Kaneriya, MD, MBA **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M11639 - Name: Metabolic Diseases - Relevance: HIGH - As Found: Metabolic Diseases - ID: M4113 - Name: Aneurysm - Relevance: HIGH - As Found: Aneurysm - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009422 - Term: Nervous System Diseases - ID: D000000783 - Term: Aneurysm - ID: D000008659 - Term: Metabolic Diseases ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05779579 **Brief Title:** Study of HS-10517 in Chinese Adult Participants **Official Title:** A Randomized, Double-blind, Placebo-controlled Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Primary Efficacy of HS-10517 in Chinese Adult Participants #### Organization Study ID Info **ID:** HS-10517-101 #### Organization **Class:** INDUSTRY **Full Name:** Jiangsu Hansoh Pharmaceutical Co., Ltd. ### Status Module #### Completion Date **Date:** 2023-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-04-03 **Type:** ACTUAL **Last Update Submit Date:** 2023-03-30 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-05-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-02-01 **Type:** ACTUAL **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2023-03-22 **Type:** ACTUAL **Study First Submit Date:** 2023-01-16 **Study First Submit QC Date:** 2023-03-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Jiangsu Hansoh Pharmaceutical Co., Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A Phase I/II, randomized, double-blind, placebo-controlled study to evaluate safety, tolerability, pharmacokinetics and primary efficacy of HS-10517 in Chinese adult participants. ### Conditions Module **Conditions:** - COVID-19 **Keywords:** - HS-10517 - 3CL protease inhibitor - single ascending dose - multiple ascending dose - phase 2 study - dose exploration - Chinese - COVID-19 ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** OTHER #### Enrollment Info **Count:** 340 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Dose level 1 of HS-10517 Tablets，Dose 1 **Intervention Names:** - Drug: HS-10517 Dose 1 **Label:** HS-10517 Dose 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Dose level 1 of HS-10517 Tablets，Dose 2 **Intervention Names:** - Drug: HS-10517 Dose 2 **Label:** HS-10517 Dose 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Dose level 1 of HS-10517 Tablets，Dose 3 **Intervention Names:** - Drug: HS-10517 Dose 3 **Label:** HS-10517 Dose 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Dose level 1 of HS-10517 Tablets，Dose 4 **Intervention Names:** - Drug: HS-10517 Dose 4 **Label:** HS-10517 Dose 4 **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Dose level A of placebo **Intervention Names:** - Drug: Placebo **Label:** Placebo Comparator **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - HS-10517 Dose 1 **Description:** HS-10517 Dose 1+Ritonavir **Name:** HS-10517 Dose 1 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - HS-10517 Dose 2 **Description:** HS-10517 Dose 2+Ritonavir **Name:** HS-10517 Dose 2 **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - HS-10517 Dose 3 **Description:** HS-10517 Dose 3+Ritonavir **Name:** HS-10517 Dose 3 **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - HS-10517 Dose 4 **Description:** HS-10517 Dose 4+Ritonavir **Name:** HS-10517 Dose 4 **Type:** DRUG #### Intervention 5 **Arm Group Labels:** - Placebo Comparator **Description:** Dose level A of placebo **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The definition of adverse event \[AE\] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The definition of serious adverse event \[SAE\] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. **Measure:** The incidence and severity of adverse events (AE), serious adverse events (SAE) and adverse events leading to withdrawal from the trial and the correlation with the investigational drug in single ascending dose (SAD) **Time Frame:** Day 1 to Day 5 **Measure:** Number of participants with clinically significant change from baseline in vital signs in SAD **Time Frame:** Day 1 to Day 5 **Description:** Criteria for clinically significant changes in 12-lead ECG are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is \>450 msec; or an absolute QTc value is ≥500 msec for any scheduled 12-lead ECG. **Measure:** Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in SAD **Time Frame:** Day 1 to Day 5 **Measure:** Number of participants with clinically significant abnormalities in laboratory examination in SAD **Time Frame:** Day 1 to Day 5 **Measure:** Number of participants with clinically significant abnormalities in physical examination in SAD **Time Frame:** Day 1 to Day 5 **Description:** The definition of adverse event \[AE\] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The definition of serious adverse event \[SAE\] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. **Measure:** The incidence and severity of adverse events (AE), serious adverse events (SAE) and adverse events leading to withdrawal from the trial and the correlation with the investigational drug in multiple ascending dose (MAD) **Time Frame:** Day 1 to Day 14 **Measure:** Number of participants with clinically significant change from baseline in vital signs in MAD **Time Frame:** Day 1 to Day 14 **Description:** Criteria for clinically significant changes in 12-lead ECG are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is \>450 msec; or an absolute QTc value is ≥500 msec for any scheduled 12-lead ECG. **Measure:** Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in MAD **Time Frame:** Day 1 to Day 14 **Measure:** Number of participants with clinically significant abnormalities in laboratory examination in MAD **Time Frame:** Day 1 to Day 14 **Measure:** Number of participants with clinically significant abnormalities in physical examination in MAD **Time Frame:** Day 1 to Day 14 **Description:** The definition of adverse event \[AE\] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The definition of serious adverse event \[SAE\] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. **Measure:** The incidence and severity of adverse events (AE), serious adverse events (SAE) and adverse events leading to withdrawal from the trial and the correlation with the investigational drug in supratherapeutic exposure (SE) **Time Frame:** Day 1 to Day 13 **Measure:** Number of participants with clinically significant change from baseline in vital signs in SE **Time Frame:** Day 1 to Day 13 **Description:** Criteria for clinically significant changes in 12-lead ECG are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is \>450 msec; or an absolute QTc value is ≥500 msec for any scheduled 12-lead ECG. **Measure:** Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) findings in SE **Time Frame:** Day 1 to Day 13 **Measure:** Number of participants with clinically significant abnormalities in laboratory examination in SE **Time Frame:** Day 1 to Day 13 **Measure:** Number of participants with clinically significant abnormalities in physical examination in SE **Time Frame:** Day 1 to Day 13 **Measure:** Percentage of participants with a negative RT-PCR test through day 5-modified intent-to-treat (mITT) population. **Time Frame:** Day 1 to Day 5 #### Secondary Outcomes **Description:** The maximum observed plasma concentration \[Cmax\] is estimated based on the plasma concentrations. **Measure:** Maximum plasma concentration (Cmax) in SAD **Time Frame:** Day 1 to Day 5 **Description:** Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence. **Measure:** Time for Cmax (tmax) in SAD **Time Frame:** Day 1 to Day 5 **Description:** AUC0-last is summarized by dosing regimen and determined by linear/log trapezoidal method. **Measure:** Area under the concentration time profile from time 0 to the time of last quantifiable plasma concentration (AUC0-last) in SAD **Time Frame:** Day 1 to Day 5 **Description:** AUC0-inf is summarized by dosing regimen and determined by linear/log trapezoidal method. **Measure:** Area under the concentration time profile from time 0 to infinity (AUC0-inf) in SAD **Time Frame:** Day 1 to Day 5 **Measure:** Terminal rate constant (λz) in SAD **Time Frame:** Day 1 to Day 5 **Measure:** Terminal half-life (t1/2) in SAD **Time Frame:** Day 1 to Day 5 **Measure:** Apparent clearance (CL/F) in SAD **Time Frame:** Day 1 to Day 5 **Measure:** Apparent volume of distribution (Vd/F) in SAD **Time Frame:** Day 1 to Day 5 **Measure:** Mean residence time (MRT) in SAD symptoms to the sustained clinical resolution within 28 days（Phase II） **Time Frame:** Day 1 to Day 5 **Description:** The maximum observed plasma concentration \[Cmax\] is estimated based on the plasma concentrations. **Measure:** Maximum plasma concentration (Cmax) in first dose of MAD **Time Frame:** Day 1 to Day 14 **Description:** Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence. **Measure:** Time for Cmax (tmax) in first dose of MAD **Time Frame:** Day 1 to Day 14 **Description:** AUC0-24 is summarized by dosing regimen and determined by linear/log trapezoidal method. **Measure:** Area under the concentration time profile from time 0 to 24 hours in first dose of MAD **Time Frame:** Day 1 to Day 14 **Description:** AUC0-12 is summarized by dosing regimen and determined by linear/log trapezoidal method. **Measure:** Area under the concentration time profile from time 0 to 12 hours in first dose of MAD **Time Frame:** Day 1 to Day 14 **Measure:** Maximum plasma concentration at steady state (Css,max) in last dose of MAD **Time Frame:** Day 1 to Day 14 **Measure:** Time for Cmax at steady state (tss,max) in last dose of MAD **Time Frame:** Day 1 to Day 14 **Measure:** Minimum plasma concentration at steady state (Css,min) in last dose of MAD **Time Frame:** Day 1 to Day 14 **Measure:** Area under the concentration time profile in one dosing interval at steady state (AUCss) in last dose of MAD **Time Frame:** Day 1 to Day 14 **Measure:** Apparent clearance at steady state (CLss/F) in last dose of MAD **Time Frame:** Day 1 to Day 14 **Measure:** Degree of accumulation after multiple doses (RAC, including RAUC and RCmax) in last dose of MAD **Time Frame:** Day 1 to Day 14 **Description:** The maximum observed plasma concentration \[Cmax\] is estimated based on the plasma concentrations. **Measure:** Maximum plasma concentration (Cmax) in SE **Time Frame:** Day 1 to Day 13 **Description:** Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence **Measure:** Time for Cmax (tmax) in SE **Time Frame:** Day 1 to Day 13 **Description:** AUC0-last is summarized by dosing regimen and determined by linear/log trapezoidal method **Measure:** Area under the concentration time profile from time 0 to the time of last quantifiable plasma concentration (AUC0-last) in SE **Time Frame:** Day 1 to Day 13 **Description:** AUC0-inf is summarized by dosing regimen and determined by linear/log trapezoidal method **Measure:** Area under the concentration time profile from time 0 to infinity (AUC0-inf) in SE **Time Frame:** Day 1 to Day 13 **Measure:** Terminal rate constant (λz) in SE **Time Frame:** Day 1 to Day 13 **Measure:** Terminal half-life (t1/2) in SE **Time Frame:** Day 1 to Day 13 **Measure:** Apparent clearance (CL/F) in SE **Time Frame:** Day 1 to Day 13 **Measure:** Apparent volume of distribution (Vd/F) in SE **Time Frame:** Day 1 to Day 13 **Measure:** Mean residence time (MRT) in SE **Time Frame:** Day 1 to Day 13 **Description:** All of the 11 COVID-19-related symptoms consist of stuffy or running nose, sore throat, shortness of breath, cough, muscle or body aches, headache, chills or shivering, feeling hot or feverish, nausea, vomiting, diarrhea. Sustained resolution is defined as when all targeted symptoms were scored as 0 for 2 consecutive days. **Measure:** Time to sustained resolution of 11 COVID-19 symptoms within 28 days **Time Frame:** Day 1 to Day 28 **Measure:** Change of viral load over time compared to baseline **Time Frame:** Day 1 to Day 28 **Measure:** Time to the first negative RT-PCR test **Time Frame:** Day 1 to Day 28 **Description:** virological response means the rate of negative RT-PCR test **Measure:** Virological response at each time point after randomization **Time Frame:** Day 1 to Day 28 **Description:** Sustained alleviation of 11 targeted COVID-19 signs/symptoms was defined as the event occurring on the first 2 consecutive days when 11 targeted symptoms scored as moderate or severe at the time of enrollment were scored as mild or absent and those scored mild or absent at the time of enrollment were scored as absent. The first day of the 2 consecutive-day period was considered date of first event. Time to sustained recovery \[event\] was calculated as first event date minus first dose date plus 1, for participants with event. For participants who completed Day 28 or discontinued the study before Day 28 without sustained resolution \[censored\], time was calculated as censoring date \[last date on which symptom recovery was assessed\] minus first dose date plus 1 or Day 25 whichever occurred first. **Measure:** Time to sustained alleviation of 11 targeted COVID-19 signs/symptoms within 28 days **Time Frame:** Day 1 to Day 28 **Measure:** Time to sustained resolution of each targeted COVID-19 symptom **Time Frame:** Day 1 to Day 28 **Description:** 11 targeted COVID-19 related clinical symptoms) from baseline up to 28 days **Measure:** Change of the score of each COVID-19 symptom **Time Frame:** Day 1 to Day 28 **Description:** All 4 inclusion criteria should be met in severe cases: positive RT-PCR test; respiratory distress \[respiratory rate \> 30 times/min\]; hypoxia \[resting oxygen saturation \< 93% or arterial partial pressure of oxygen / oxygen concentration \< 300 mmHg\]; COVID-19 featured lung lesions in chest X-ray image. **Measure:** Proportion of severe cases within 28 days **Time Frame:** Day 1 to Day 28 **Measure:** The plasma concentration of HS-10517 in COVID-19 patients in phase II study **Time Frame:** Day 1 to Day 7 **Measure:** Population apparent clearance (CL/F) of COVID-19 patients in phase II study **Time Frame:** Day 1 to Day 7 **Measure:** Population apparent volume of distribution (Vd/F) of COVID-19 patients in phase II study **Time Frame:** Day 1 to Day 7 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Inclusion Criteria for SAD, MAD and SE： * Subjects should fully understand the content, process and possible adverse reactions of the study, and voluntarily sign the informed consent form; * The age at the time of signing the informed consent is between 18 and 45 years old (including the critical value) * Subjects with negative COVID-19 nucleic acid detection in screening period; * The body mass index (BMI=body weight \[kg\]/height2 \[m2\]) at screening is 19\~27kg/m2 (including the critical value), and the weight of men is ≥ 50kg, and that of women is ≥ 40kg; * The blood pregnancy test of female subjects in the screening period and the baseline period is negative; * Female subjects must agree to take effective contraceptive measures from the date of signing the informed consent form to 30 days after the last administration: 1. Those with fertility: from the date of signing the informed consent form to 30 days after the last administration, ① avoid pregnancy, ② if having sex with the opposite sex, agree to continue to use one or more forms of effective contraception (such as verified intrauterine devices, bilateral tubal ligation or correct use of condoms, excluding any form of hormonal contraceptives). If the male partner has undergone an effective sterilization operation, additional effective contraception measures should be taken when the sperm is uncertain); 2. Non-fertility: ① Postmenopausal (spontaneous amenorrhea ≥ 12 months, or spontaneous amenorrhea ≥ 6 months and FSH\>40 IU/L, without other obvious pathological or physiological reasons) before screening; Or ② documented surgical sterilization (such as hysterectomy, bilateral salpingectomy or bilateral oophorectomy, etc.); * Male subjects (including their female partners) must agree to take effective contraceptive measures from the date of signing the informed consent form to 30 days after the last administration: 1. Those who are fertile must agree to use condoms correctly. If their female partners are women of child-bearing age and have fertility (have not undergone hysterectomy, bilateral salpingectomy or bilateral oophorectomy and have no medical proven ovarian failure), their female partners must take effective contraceptive measures (such as oral/injection/vaginal or implantable hormone contraceptives, or other physical barrier, surgery and other female contraceptive methods) within 30 days after the last administration; 2. Those who are infertile, such as those who have undergone effective sterilization operations, take additional effective contraceptive measures when they are not sure whether they have sperm); * Male subjects agree to avoid donating sperm within 30 days from the initiation of drug administration until the last administration. Inclusion Criteria for Phase II dose exploration: * Subjects should fully understand the content, process and possible adverse reactions of the study, and voluntarily sign the informed consent form; * The age at the time of signing the informed consent is ≥ 18 years old; * In the first 2 days (48 hours) before randomization, COVID-19 nucleic acid detected by RT-PCR is positive; * During the screening period, the subject is assessed by the research doctor as a patient with mild to moderate COVID-19 infection; * During the screening period, the subject is assessed by the research doctor and show symptoms/signs of COVID-19 infection for the first time within 2 days before randomization; * At least one of targeted COVID-19 symptoms exists within the first 24 hours of randomization and meets the corresponding severity; * Female subjects must agree to take the drug from the date of signing the informed consent form to 30 days after the last administration; Effective contraceptive measures: Those with fertility: from the date of signing the informed consent form to 30 days after the last administration, ① avoid pregnancy, ② if having sex with the opposite sex, agree to continue to use one or more forms of effective contraception (such as verified intrauterine devices, bilateral tubal ligation or correct use of condoms, excluding any form of hormonal contraceptives). If the male partner has undergone an effective sterilization operation, additional effective contraception measures should be taken when the sperm is uncertain); * Male subjects (including their female partners) agree to take effective contraceptive measures from the date of signing the informed consent form to 30 days after the last administration: 1. Those who are fertile must agree to use condoms correctly. If their female partners are women of child-bearing age and have fertility (have not undergone hysterectomy, bilateral salpingectomy or bilateral oophorectomy and have no medical proven ovarian failure), their female partners must take effective contraceptive measures (such as oral/injection/vaginal or implantable hormone contraceptives, or other physical barrier, surgery and other female contraceptive methods) within 30 days after the last administration 2. Those who are infertile, such as those who have undergone effective sterilization, take additional effective contraceptive measures when they are not sure whether they have sperm). * The pregnancy test of female subjects in the screening period and the baseline period is negative; * Male subjects agree to avoid donating sperm within 30 days from the start of administration until the last administration Exclusion Criteria of SAD, MAD and SE: * According to the judgment of the principal investigator, the participant is accompanied with suspected COVID-19 related clinical symptoms/signs; * During screening, those who are judged to be clinically significant by the principal investigator through medical history inquiry, physical examination, vital signs, blood oxygen saturation (SpO2), laboratory examination, 12-lead electrocardiogram (ECG), abdominal ultrasound, chest X-ray examination, etc; * Participants with clinically significant diseases (such as neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal muscle system, endocrine and metabolic system, blood system, skin disease, immune system, tumor, etc.) are evaluated by the researcher as not suitable for this study; * Previous major surgery, or according to the judgment of the principal investigator, there is any physiological or disease or condition that may affect the absorption of the study drug (such as gastrectomy, cholecystectomy, enterotomy, etc.); * According to the judgment of the principal investigator, there is any physical or psychological disease or condition that may increase the risk of the test, affect the compliance of the subject with the other case, or affect the subject's completion of the test; * Within 2 weeks or 5 half-life (whichever is longer) before screening, and during the whole study period, it is expected to take any medicine and health care products, including prescription drugs, over-the-counter drugs and Chinese herbal medicine (including oral contraceptives, external spermicide, drugs with systemic therapeutic effects through percutaneous absorption and St. John's wort); * Participants have participated in any clinical study or taken study drugs within 3 months before screening; * Have a history of vaccination within 30 days before screening, or plan to have a vaccination throughout the study period; * Difficult in blood sample collection, unable to tolerate multiple venous blood collection and any contraindication of blood sample collection; * Large amount of blood loss or donation (more than 250mL) within 3 months before screening; * At screening, 12-lead ECG is abnormal and had clinical significance according to the judgment of the researcher, such as the QT interval (QTcB) corrected by Bazett (formula QT/RR0.5), the absolute value of QTcB in males is more than 450ms, and the absolute value of QTcB in females is more than 470ms; * When screening, endogenous creatinine clearance rate is less than 80mL/min, according to Cockcroft-Gault formula: endogenous creatinine clearance rate (mL/min)=(140 - age) × body weight (kg) 72 × serum creatinine concentration (mg/dL) (female × 0.85); * During the screening period and/or the baseline period, the blood pressure and pulse are within the following range: systolic blood pressure \<90 mmHg or ≥ 140 mmHg, diastolic blood pressure \<60 mmHg or ≥ 90 mmHg, pulse \<55 bpm or \>100 bpm; * Have a history of drug dependence or drug abuse in the past, or have a positive urine drug test during screening; * Those who have a history of severe allergy to drugs, food and articles (including allergy to latex, dust mites, pollen, etc.), or are known to be allergic to the test drug ingredients; * Within 2 weeks before screening, dieting or receiving dietary treatment for whatever reason, or major changes in dietary habits; * Have a history of alcoholism in the past (drinking more than 14 units of alcohol per week on average), or drink more than 14 units of alcohol per time in the past two weeks (1 unit=285mL of beer, 25mL of spirits, 125mL of wine), or cannot stop drinking alcohol products during the test; Or positive alcohol breath test during screening; * Those who smoke more than 5 cigarettes per day on average in the three months before screening, or who cannot stop using any tobacco products during the test; * Within 2 weeks before screening, subjects ingested foods that may affect drug metabolism, such as grapefruit juice; * The average daily intake of coffee, tea, cola or other caffeinated drinks exceeds 6 cups (about 250mL per cup) within 3 months before screening; * Those who have difficulty swallowing solid preparations such as tablets; * Female subjects are in pregnancy or lactation at the time of screening; * This study may not be completed due to other reasons or the researcher judges that it is not suitable for participants. Exclusion Criteria for Phase II dose exploration: * The medical condition indicates that COVID-19 causes clinical signs of severe systemic diseases, such as respiratory rate ≥ 30 times/minute, heart rate ≥ 125 times/minute, blood oxygen saturation (SpO2) ≤ 93% or PaO2/FiO2\<300 mmHg within 24 hours before randomization (under indoor air conditions at rest), and it is urgent or expected to require nasal high-flow oxygen therapy or non-invasive positive pressure ventilation, invasive mechanical ventilation or ECMO. * According to the judgment of the researcher, the medical condition suggests that COVID-19 may develop into severe/critical status in the next 48 hours; * Other than COVID-19, suspected or confirmed acute systemic infection (such as combined influenza and bacterial infection) may interfere with the evaluation of the research intervention response. * Known history of active liver disease (excluding nonalcoholic fatty liver), including acute or chronic active hepatitis B or C, primary biliary cirrhosis, Child-Pugh grade B or C or acute liver failure. * The patient is undergoing dialysis or is known to have moderate to severe renal damage (that is, within 6 months before the screening visit, the CKD-EPI formula based on serum creatinine eGFR \< 45mL/min/1.73m2). * They received anti-COVID-19 drugs (excluding NSAIDs) within 14 days before randomization. * Has received (within 30 days before randomization or within the half-life of 5 drugs, whichever is longer) or is expected to receive COVID-19 monoclonal antibody or COVID-19 convalescence plasma treatment during the study period. * Any anti-COVID-19 vaccine was inoculated within 3 months before randomization. * Subjects who have to use potent CYP3A4/5 inhibitors and/or potent CYP3A4/5 inducers from 7 days before screening to 7 days after the last administration for various reasons. * Subjects have major diseases (such as acute myocardial infarction, stroke, malignant tumor, etc.) within 30 days before signing the informed consent form; * Those who have difficulty swallowing solid preparations such as tablets; * At the time of screening, the female subjects are in pregnancy or lactation. **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Linlin Song **Phone:** 0531-89268311 **Role:** CONTACT #### Locations **Location 1:** **City:** Jinan **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Linlin Song - **Phone:** 053189268311 - **Role:** CONTACT **Country:** China **Facility:** The First Affiliated Hospital of Shandong First Medical University Shandong Provincial Qianfoshan Hospital **State:** Shandong **Status:** RECRUITING ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21394 - Name: Ritonavir - Relevance: LOW - As Found: Unknown - ID: M19609 - Name: HIV Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M14343 - Name: Protease Inhibitors - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05623579 **Brief Title:** Education on BDNF on Pain Levels **Official Title:** Effect of Therapeutic Education on Pain Intensity and BDNF Levels in Patients With Chronic Pain #### Organization Study ID Info **ID:** 2022A36005 #### Organization **Class:** OTHER **Full Name:** Universidad Autonoma de Madrid ### Status Module #### Completion Date **Date:** 2025-05-28 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-30 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-29 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12-30 **Type:** ESTIMATED #### Start Date **Date:** 2023-10-01 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2022-11-21 **Type:** ACTUAL **Study First Submit Date:** 2022-10-25 **Study First Submit QC Date:** 2022-11-18 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Universidad Rey Juan Carlos #### Lead Sponsor **Class:** OTHER **Name:** Universidad Autonoma de Madrid #### Responsible Party **Investigator Affiliation:** Universidad Autonoma de Madrid **Investigator Full Name:** Raúl Ferrer-Peña **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The promotion of neuroplasticity in conjunction with strategies for restructuring maladaptive cognitions that largely cause the activation of neural networks that contribute to the perpetuation of pain is therefore a fundamental neurophysiological principle for establishing a neurophysiological basis for pain. perpetuation of pain, is therefore a fundamental neurophysiological principle for establishing physiotherapy therapeutic to establish therapeutic strategies from physiotherapy that contribute to improve the quality of life of patients with chronic pain. patients with chronic pain. Based on the theory that neurotrophic factors such as BDNF play a fundamental role in the initiation and or maintenance of hyperexcitability of central neurons in pain, we consider that the levels of this neurotrophic factor, such as BDNF, may have an important role in the perpetuation of pain. that the levels of this neurotrophic factor may be modified by the application of a therapeutic education protocol, favoring therapeutic education protocol, favoring a reduction in pain intensity. ### Conditions Module **Conditions:** - Chronic Pain - Musculoskeletal Pain **Keywords:** - BDNF - Pain Neuroscience Education - Exercise ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 66 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Pain Education plus Exercise **Intervention Names:** - Behavioral: Pain Neuroscience Education - Behavioral: Exercise **Label:** Intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Exercise **Intervention Names:** - Behavioral: Exercise **Label:** Control **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention **Description:** 8 Sessions of different pain education interventions **Name:** Pain Neuroscience Education **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Control - Intervention **Description:** 12 Sessions of Aerobic Exercise **Name:** Exercise **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Pain intensity assessed with the 100 mm Visual Analog Scale, in which the patient is asked about his or her pain level at that moment, with one side being "no pain" and the other extreme being "the worst pain imaginable". **Measure:** Pain Intensity **Time Frame:** 36 weeks #### Secondary Outcomes **Description:** BDNF level measured in blood serum by ELISA kit at baseline and at the end of the intervention. **Measure:** BDNF level **Time Frame:** 36 weeks **Description:** Anxiety and depression will be assessed using the Spanish validated version of the HADS. The HADS is a self-administered measure with 14 items in total that ask the client to reflect on their mood in the past week. Seven items assess depression, 5 of which are markers for anhedonia (an inability to experience pleasure), and 2 concern appearance and feelings of slowing down. Seven items assess anxiety, of which 2 assess autonomic anxiety (panic and butterflies in the stomach), and the remaining 5 assess tension and restlessness (Dunbar, Ford, Hunt, \& Der, 2000). **Measure:** Anxiety and Depression (HADS) **Time Frame:** 36 weeks **Description:** The EQ-5D is a generic HRQoL. HRQoL that can be used both in relatively healthy individuals (general population) and in groups of patients with different pathologies. The individual assesses his or her own health status, first in levels of severity by dimensions and then on a more general visual analog scale (VAS).The third element of the EQ-5D is the index of social values that is obtained for each health state generated by the instrument. In this part of the questionnaire, the individual must mark the level of severity corresponding to his or her health status in each of the dimensions health status in each of the dimensions, referring to the same day on which the same day the questionnaire is completed. **Measure:** Quality of life (EQ-5D) **Time Frame:** 36 weeks **Description:** Pain Catastrophism will be measured with the Spanish version of the Pain Catastrophism Scale. The Pain Catastrophizing Scale (PCS) is a 13-item self-report questionnaire considered to be the most frequent and extensively studied tool to assess pain catastrophizing for chronic pain. Good levels of content and construct validity, internal consistency and test-retest reliability of the PCS have been reported in studies examining different musculoskeletal disorders and different language versions. **Measure:** Pain Catastrophism (PCS) **Time Frame:** 36 weeks **Description:** Pain severity will be measured Chronic Pain Grading Scale Description: A measure of pain intensity and interference with normal daily activities. Format: 7 items Scoring: Scores for 6 of the items range from 0 (no pain) to 10 (pain as bad as it could be). The one remaining item requires filling in the number of days that pain has kept respondents from their typical activities. Scores classify respondents into one of 4 levels of pain intensity and activity interference: Low disability and low pain intensity Low disability and high pain intensity High disability and moderate limitation of activities High disability and severe limitation of activities **Measure:** Pain Severity Level (GCPS-R) **Time Frame:** 36 weeks **Description:** measured with a finger pulse oximeter: A normal ABG oxygen level for healthy lungs falls between 80 and 100 millimeters of mercury (mm Hg). **Measure:** Oxygen Saturation (SpO2) **Time Frame:** 36 weeks **Description:** measured with a finger pulse oximeter: A normal Heart Rate is between 60 and 120 pulse per minute. **Measure:** Heart rate (HR) **Time Frame:** 36 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * males and females aged 18 to 65 years with musculoskeletal pain for a minimum of 3 months * patients recruited by information pamphlets from the university clinic of the Rey Juan Carlos University, and CSEU La Salle * not having received physiotherapy treatment for this same process in the last 3 months. * ability to perform all the clinical tests and to understand the study process, as well as to obtain informed consent. Exclusion Criteria: - Systemic, neurological, oncological or inflammatory diseases; psychiatric pathologies, pregnancy, type II diabetes. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Alcorcón **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Josue Fernández-Carnero - **Role:** CONTACT **Country:** Spain **Facility:** Clínica URJC **State:** Madrid **Status:** NOT_YET_RECRUITING **Zip:** 28922 **Location 2:** **City:** Madrid **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Luis Matesanz - **Phone:** +34607712148 - **Role:** CONTACT ***Contact 2:*** - **Name:** Silvia Di Bonaventura - **Role:** SUB_INVESTIGATOR **Country:** Spain **Facility:** IRF La Salle **Status:** RECRUITING **Zip:** 28023 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Mills SEE, Nicolson KP, Smith BH. Chronic pain: a review of its epidemiology and associated factors in population-based studies. Br J Anaesth. 2019 Aug;123(2):e273-e283. doi: 10.1016/j.bja.2019.03.023. Epub 2019 May 10. **PMID:** 31079836 **Citation:** Andias R, Neto M, Silva AG. The effects of pain neuroscience education and exercise on pain, muscle endurance, catastrophizing and anxiety in adolescents with chronic idiopathic neck pain: a school-based pilot, randomized and controlled study. Physiother Theory Pract. 2018 Sep;34(9):682-691. doi: 10.1080/09593985.2018.1423590. Epub 2018 Jan 10. **PMID:** 29319386 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009135 - Term: Muscular Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M29442 - Name: Chronic Pain - Relevance: HIGH - As Found: Chronic Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M29444 - Name: Musculoskeletal Pain - Relevance: HIGH - As Found: Musculoskeletal Pain - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M12092 - Name: Muscular Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000059352 - Term: Musculoskeletal Pain - ID: D000059350 - Term: Chronic Pain ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04970979 **Brief Title:** Exercise Adherence in Home-based Cardiac Rehabilitation **Official Title:** Influencing Factors of Exercise Adherence in Home-based Cardiac Rehabilitation in Patients With Coronary Artery Disease #### Organization Study ID Info **ID:** IRB00006761-M2021057 #### Organization **Class:** OTHER **Full Name:** Peking University Third Hospital ### Status Module #### Completion Date **Date:** 2022-02-18 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2021-07-21 **Type:** ACTUAL **Last Update Submit Date:** 2021-07-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-02-18 **Type:** ESTIMATED #### Start Date **Date:** 2021-07-18 **Type:** ESTIMATED **Status Verified Date:** 2021-06 #### Study First Post Date **Date:** 2021-07-21 **Type:** ACTUAL **Study First Submit Date:** 2021-06-27 **Study First Submit QC Date:** 2021-07-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Peking University Third Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The study will investigate the influencing factors of exercise adherence of home-based cardiac rehabilitation in patients with coronary artery disease. **Detailed Description:** The study will conduct a quantitative questionnaire survey. Patients with coronary artery disease in home-based cardiac rehabilitation will receive investigation of the influencing factors of exercise adherence. ### Conditions Module **Conditions:** - Coronary Artery Disease **Keywords:** - Coronary artery disease - Home-based cardiac rehabilitation - Exercise adherence ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 300 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** patients with coronary artery disease **Intervention Names:** - Other: survey **Label:** patients with coronary artery disease ### Interventions #### Intervention 1 **Arm Group Labels:** - patients with coronary artery disease **Description:** questionnaire about the influencing factors of home-based cardiac rehabilitation **Name:** survey **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Influencing factors of exercise adherence in home-based cardiac rehabilitation **Measure:** Influencing factors of exercise adherence **Time Frame:** The influencing factors of exercise adherence in home-based cardiac rehabilitation will be measured by the Theory of Planned Behavior Questionnaire through study completion, an average of 1 year **Description:** Adherence of home-based exercise training **Measure:** Exercise adherence **Time Frame:** The exercise adherence will be measured by the Home-based Exercise Training Adherence Questionnaire through study completion, an average of 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosis of coronary artery disease; * Age ≤75 years old; * Participated in home-based cardiac rehabilitation ≥12 weeks; * Volunteer to participate in this study. Exclusion Criteria: * Have other serious acute or chronic diseases; * Have severe audio-visual or speech impairments that may affect understanding and answering questions. **Maximum Age:** 75 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** patients with coronary artery disease ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Wei Zhao **Phone:** 010-18600017812 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Wen Guo **Phone:** 010-18813119215 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Name:** Wei Zhao - **Phone:** 010-18600017812 - **Role:** CONTACT ***Contact 2:*** - **Name:** Wen Guo - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Wei Zhao - **Role:** SUB_INVESTIGATOR **Country:** China **Facility:** Peking University Third Hospital **Zip:** 100191 #### Overall Officials **Official 1:** **Affiliation:** Peking University Third Hospital **Name:** Wei Zhao **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000001161 - Term: Arteriosclerosis - ID: D000001157 - Term: Arterial Occlusive Diseases - ID: D000014652 - Term: Vascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M6549 - Name: Coronary Disease - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M6546 - Name: Coronary Artery Disease - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M19506 - Name: Myocardial Ischemia - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M4469 - Name: Arteriosclerosis - Relevance: LOW - As Found: Unknown - ID: M4465 - Name: Arterial Occlusive Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003324 - Term: Coronary Artery Disease - ID: D000017202 - Term: Myocardial Ischemia - ID: D000003327 - Term: Coronary Disease ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05406479 **Acronym:** BE-PEOPLE P2 **Brief Title:** Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy (Phase 2) **Official Title:** Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy: Phase 2 Study #### Organization Study ID Info **ID:** BE-PEOPLE Phase 2 #### Organization **Class:** OTHER **Full Name:** Institute of Tropical Medicine, Belgium ### Status Module #### Completion Date **Date:** 2023-01-26 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-12 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-01-26 **Type:** ACTUAL #### Start Date **Date:** 2022-07-14 **Type:** ACTUAL **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2022-06-06 **Type:** ACTUAL **Study First Submit Date:** 2022-05-20 **Study First Submit QC Date:** 2022-06-02 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Damien Foundation #### Lead Sponsor **Class:** OTHER **Name:** Institute of Tropical Medicine, Belgium #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study will evaluate a combination of bedaquiline and rifampicin as post exposure prophylaxis (PEP) for leprosy in Comoros. It will be a follow-up to the PEOPLE trial on PEP with rifampicin, which is ending in 2022. This new trial will be called the 'Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy' or 'BE-PEOPLE' trial. There will be two main study arms, a comparator arm based on the current WHO recommendation of providing a single dose of rifampicin (10 mg/kg) to close contacts of leprosy patients and an intervention arm in which this regimen will be reinforced with bedaquiline, 400 or 800 mg depending on weight, to be repeated once after four weeks for household contacts. The main study will be preceded by a phase 2 safety study. **Detailed Description:** Given the fact that the investigators are going to provide to healthy people a drug that has not been used before for this indication and which has only been conditionally approved for use in multi-drug resistant tuberculosis, they have first foreseen a phase 2 study in which BE-PEP will be provided to a limited number of contacts and in which safety will be closely monitored and evaluated by an independent data and safety monitoring board (DSMB). This will be done in a small village that is part arm 1 of the PEOPLE trial in which 8 new cases have been diagnosed since 2019 but no PEP has been provided. The investigators will conduct door-to-door screening in this village in June 2022 and offer a single dose of BE-PEP to a random sample of 150 people screened aged 5 years and above not meeting the exclusion criteria (active tuberculosis (TB) or leprosy or previously treated leprosy, known liver function or cardiac abnormalities, not able to swallow 100 mg bedaquiline tablets). Participants will be followed up closely with active monitoring for adverse events, including measurement of the corrected QT interval and liver function before and after administration, as well as gastro-intestinal (nausea, vomiting), nervous system-related (headache, dizziness) and cutaneous reactions. The remainder of the population of this village aged two years and above will be offered single dose rifampicin as per WHO recommendations. In a randomly sampled subset of 150 individuals receiving rifampicin only, the same stringent monitoring with ECG and liver function tests also applied in those receiving BE-PEP will be performed. ### Conditions Module **Conditions:** - Leprosy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 321 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Eligible participants will receive one dose of Bedaquiline plus Rifampicin **Intervention Names:** - Drug: BE-PEP (Bedaquiline) - Drug: BE-PEP (Rifampicine) **Label:** BE-PEP (Bedaquiline Post-Exposure Prophylaxis) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Eligible participants will receive one dose of Rifampicin (WHO recommendation) **Intervention Names:** - Drug: SDR-PEP **Label:** SDR-PEP (Single-Dose Rifampicin Post-Exposure Prophylaxis) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - BE-PEP (Bedaquiline Post-Exposure Prophylaxis) **Description:** Single dose of Bedaquiline **Name:** BE-PEP (Bedaquiline) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - SDR-PEP (Single-Dose Rifampicin Post-Exposure Prophylaxis) **Description:** Single dose of Rifampicin **Name:** SDR-PEP **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - BE-PEP (Bedaquiline Post-Exposure Prophylaxis) **Description:** Single dose of Rifampicin **Name:** BE-PEP (Rifampicine) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Mean difference in QTc interval between the two arms 24 hours after treatment administration **Measure:** Mean difference in QTc interval between the two arms 24 hours after treatment administration **Time Frame:** 24 hours after treatment administration **Description:** Occurence of any of the following predetermined study stopping criteria, which will trigger an immediate pause on enrollment: 1. Death of a participant considered related to study drug 2. One or more participants experience an Serious Adverse Event (SAE) or Grade 4 Adverse Event (AE) or a persistent (upon repeat testing) Grade 4 laboratory abnormality that is determined to be related to study drug 3. Three or more participants experience a Grade 3 or greater AE of the same type (as per medical judgement) that is determined to be related to study drug 4. Three or more participants experience a persistent (upon repeat testing) Grade 3 laboratory abnormality related to the same laboratory parameter and considered to be related to study drug 5. Two or more participants experience QTc \> 500 ms 6. One or more participants has Aspartate transaminase (AST) or Alanine transaminase (ALT) \> 8x Upper limit of normal (ULN), in absence of causative explanation **Measure:** Occurence of any predetermined study stopping criteria, which will trigger an immediate pause on enrollment **Time Frame:** Until day 30 after treatment administration #### Secondary Outcomes **Description:** To determine the baseline frequency of ALT in the population. **Measure:** Baseline frequency of ALT in the population **Time Frame:** At baseline **Description:** To determine baseline frequency of AST elevations in the population **Measure:** Baseline frequency of AST elevations in the population **Time Frame:** At baseline **Description:** To determine baseline frequency of QTc prolongations in the population **Measure:** Baseline frequency of QTc prolongations in the population **Time Frame:** At baseline **Description:** Post administration QTc prolongation **Measure:** Post administration QTc prolongation **Time Frame:** 24 hours after treatment administration **Description:** Post administration ALT level **Measure:** Post-administration ALT level **Time Frame:** Day 14 after treatment administration **Description:** Post-administration AST level **Measure:** Post-administration AST level **Time Frame:** Day 14 after treatment administration **Description:** Frequency of potentially common adverse events such as gastro-intestinal (nausea, vomiting), nervous system-related (headache, dizziness) and cutaneous reactions **Measure:** Frequency of potentially common adverse events such as gastro-intestinal (nausea, vomiting), nervous system-related (headache, dizziness) and cutaneous reactions **Time Frame:** Until day 30 after treatment administration **Description:** Occurrence of any (serious)AEs **Measure:** Occurrence of any (serious)AEs **Time Frame:** Until day 30 after treatment administration ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Being a permanent resident of the study village, in good state of health 2. Able and willing to provide informed consent 3. Age 5 years or above and weight of 20 kg or above Exclusion Criteria: 1. Signs of active leprosy 2. Signs of active pulmonary tuberculosis (cough ≥2 weeks duration) 3. Signs of active extra-pulmonary tuberculosis (bluish-red nodules that cover the lymph nodes, bones or joints, or cervical glands with discharge) 4. History of liver- or kidney disease 5. Allergy to rifampicin or bedaquiline 6. Having received rifampicin or bedaquiline (if applicable) in the last 2-year period 7. Not able to swallow bedaquiline 100 mg tablets 8. Self-reported (suspected) pregnancy or breastfeeding 9. Concurrent (within the last three week period before D0) use of medications not included in the safe list (for bedaquiline only) 10. QT-prolongation of ≥450 msec in baseline ECG within the last week. 11. Jaundice or self-reported liver function abnormalities or hepatitis 12. Value of baseline ALT or AST \>3x ULN within the last week. In case only ALT is available, this would suffice for enrollment **Healthy Volunteers:** True **Minimum Age:** 5 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Gege **Country:** Comoros **Facility:** Fondation Damien **State:** Anjouan #### Overall Officials **Official 1:** **Affiliation:** Damien Foundation Comoros **Name:** Younoussa Assoumani **Role:** PRINCIPAL_INVESTIGATOR ## Document Section ### Large Document Module #### Large Docs - Date: 2023-03-01 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1039718 - Type Abbrev: Prot - Upload Date: 2023-06-07T08:11 ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2023-07-18 - Date Unknown: Unknown #### Event: RESET - Date: 2024-02-22 - Date Unknown: Unknown ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009165 - Term: Mycobacterium Infections, Nontuberculous - ID: D000009164 - Term: Mycobacterium Infections - ID: D000000193 - Term: Actinomycetales Infections - ID: D000016908 - Term: Gram-Positive Bacterial Infections - ID: D000001424 - Term: Bacterial Infections - ID: D000001423 - Term: Bacterial Infections and Mycoses - ID: D000007239 - Term: Infections ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10930 - Name: Leprosy - Relevance: HIGH - As Found: Leprosy - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M12119 - Name: Mycobacterium Infections - Relevance: LOW - As Found: Unknown - ID: M12120 - Name: Mycobacterium Infections, Nontuberculous - Relevance: LOW - As Found: Unknown - ID: M4722 - Name: Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M19252 - Name: Gram-Positive Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M12136 - Name: Mycoses - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: T2664 - Name: Hansen's Disease - Relevance: HIGH - As Found: Leprosy ### Condition Browse Module - Meshes - ID: D000007918 - Term: Leprosy ### Intervention Browse Module - Ancestors - ID: D000000995 - Term: Antitubercular Agents - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M15118 - Name: Rifampin - Relevance: LOW - As Found: Unknown - ID: M341494 - Name: Bedaquiline - Relevance: HIGH - As Found: 115 - ID: M4311 - Name: Antitubercular Agents - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000493870 - Term: Bedaquiline ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2023-07-18 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2023-07-18 - Reset Date: 2024-02-22 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - MCP Release N: Unknown - Release Date: 2024-03-12 - Reset Date: Unknown - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05299879 **Acronym:** SAINTS-A **Brief Title:** Screening for Advanced Heart Failure IN Stable ouTpatientS - The SAINTS Study **Official Title:** Screening for Advanced Heart Failure IN Stable ouTpatientS (The SAINTS Study) - Early Identification of Advanced Heart Failure #### Organization Study ID Info **ID:** RH-SAINTS-A #### Organization **Class:** OTHER **Full Name:** Rigshospitalet, Denmark ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-01 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-31 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Start Date **Date:** 2022-10-24 **Type:** ACTUAL **Status Verified Date:** 2022-10 #### Study First Post Date **Date:** 2022-03-29 **Type:** ACTUAL **Study First Submit Date:** 2022-03-07 **Study First Submit QC Date:** 2022-03-18 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Novo Nordisk A/S #### Lead Sponsor **Class:** OTHER **Name:** Rigshospitalet, Denmark #### Responsible Party **Investigator Affiliation:** Rigshospitalet, Denmark **Investigator Full Name:** Finn Gustafsson **Investigator Title:** Sponsor-Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of the Screening for Advanced heart failure IN stable ouTpatientS (SAINTS) study is to determine the prevalence of advanced heart failure (HF) in symptomatic patients with HF and reduced left ventricular ejection fraction (HFrEF), corresponding to the New York Heart Association functional class II-III. Recognition of advanced HF is a challenge for physicians and under referral for advanced management is a considerable problem. There are excellent treatment options for patients with advanced HF, i.e. heart transplantation or left ventricular assist device (LVAD) implantation, and outcomes with these therapies are considerably better if patients are treated before irreversible end-organ damage occurs. International consensus highlights the importance of timely recognition and referral of these patients to advanced HF centers. The investigators aim to screen patients with symptomatic HFrEF who are followed in Danish HF clinics in the Copenhagen region with echocardiography, cardiopulmonary exercise test, 6 minute walk test, and NT-proBNP. The investigators hypothesize that 20% of patients with symptomatic heart failure followed in HF clinics in the Copenhagen Region will fulfill the modified criteria for advanced HF from the HFA-ESC (primary end-point in the study)(Reference 1). Patients who are identified with advanced HF will be offered right heart catheterization, guided by ultrasound and inserted through the internal jugular vein, determining pulmonary capillary wedge pressure, cardiac index, central venous pressure, mean pulmonary artery pressure, and central venous oxygen saturation. Patients not fulfilling criteria for advanced HF will be offered right heart catheterization consecutively until 50 patients have been examined (this group will be a comparator group to the patients with advanced HF). Patients identified with advanced HF will be offered listing for HTx or LVAD if an indication without a contraindication is present. Patients who fulfill the primary endpoint of modified HFA-ESC criteria for advanced HF, and are ineligible for, or unwilling to undergo HTx or LVAD implantation will be invited to participate in the SAINTS B study. **Detailed Description:** Number of patients and sample size More than 3000 patients are followed in the HF clinics on Zealand including the greater Copenhagen region. The investigators plan to include 400 patients in the primary outcome analysis (SAINTS A) and hypothesize that 20% will fulfill the modified criteria for advanced HF. Statistical analysis Descriptive statistics will be reported as mean +/- standard deviation (SD) or median (interquartile range (IQR)) depending on distribution. Comparisons between groups at baseline will be performed by unpaired t-tests for normally distributed continuous variables, by the Mann-Whitney U test (Wilcoxon rank-sum) for non-normally distributed continuous variables and χ2 or Fisher's exact test for categorical variables. The primary outcome will be analyzed as the proportion n (%) of included patients who fulfill the modified HFA-ESC criteria for advanced HF. As for secondary outcomes, the investigators will analyze the proportion n (%) of patients who within the first 3 months are; 1) offered heart transplant listing, 2) offered LVAD implantation, 3) listed for HTx and 4) undergoing LVAD implantation. Further, comparisons of invasive hemodynamics, CPET measures, 6MWT, QoL and NTproBNP levels between patients with and without advanced HF will be made using an unpaired t-test or the Mann-Whitney U test for non-normally distributed continuous variables. ### Conditions Module **Conditions:** - Heart Failure With Reduced Ejection Fraction **Keywords:** - Advanced heart failure - Screening ### Design Module #### Bio Spec **Description:** Full blood **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 400 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 3 Months ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Diagnostic Test: Cardiopulmonary exercise test, NT-proBNP, Echocardiography, 6 minute walk test, Right heart catheterization **Label:** Symptomatic patients with HFrEF corresponding to NYHA II-III ### Interventions #### Intervention 1 **Arm Group Labels:** - Symptomatic patients with HFrEF corresponding to NYHA II-III **Description:** Screening for advanced HF with modified criteria from the Heart Failure Association of the European Society of Cardiology **Name:** Cardiopulmonary exercise test, NT-proBNP, Echocardiography, 6 minute walk test, Right heart catheterization **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Modified HFA-ESC criteria for advanced HF defined as: • LVEF ≤ 30% as estimated by echocardiography AND • Peak oxygen uptake (VO2peak) \< 12 ml/kg/min (14 if on betablocker) with a Respiratory Exchange Ratio (RER) \> 1.05 OR \< 50% expected for age and gender OR 6 minute walk test (6MWT) distance \< 300 meters AND • N-terminal pro B-type natriuretic peptide (NTproBNP) \> 2000 pg / ml **Measure:** Proportion of patients screened who fulfill advanced HF criteria using a modified HFA-ESC definition **Time Frame:** At time of screening #### Secondary Outcomes **Measure:** Proportion of patients offered heart transplant listing < 3 months after primary outcome **Time Frame:** 3 months after meeting modified HFA-ESC criteria for advanced HF **Measure:** Proportion of patients offered LVAD implantation < 3 months after primary outcome **Time Frame:** 3 months after meeting modified HFA-ESC criteria for advanced HF **Measure:** Proportion of patients listed for heart transplantation < 3 months after primary outcome **Time Frame:** 3 months after meeting modified HFA-ESC criteria for advanced HF **Measure:** Proportion of patients undergoing LVAD implantation < 3 months after primary outcome **Time Frame:** 3 months after meeting modified HFA-ESC criteria for advanced HF **Description:** Measured during right heart catheterization **Measure:** Pulmonary capillary wedge pressure (PCWP) in mmHg compared between patients with, and without advanced HF **Time Frame:** Within 30 days from screening **Description:** Measured during right heart catheterization **Measure:** Cardiac index (CI) in l/min/m2 compared between patients with, and without advanced HF **Time Frame:** Within 30 days from screening **Description:** Measured during right heart catheterization **Measure:** Central venous pressure (CVP) in mmHg compared between patients with, and without advanced HF **Time Frame:** Within 30 days from screening **Description:** Measured during right heart catheterization **Measure:** Mean pulmonary artery pressure (mPAP) in mmHg compared between patients with, and without advanced HF **Time Frame:** Within 30 days from screening **Description:** Measured during right heart catheterization **Measure:** Central venous oxygen saturation in % compared between patients with, and without advanced HF **Time Frame:** Within 30 days from screening **Description:** Measured during cardiopulmonary exercise test **Measure:** Peak oxygen uptake (VO2peak) in ml/kg/min compared between patients with, and without advanced HF **Time Frame:** At time of screening **Description:** The ratio between metabolic production of CO2 and the uptake of O2 measured during cardiopulmonary exercise test **Measure:** Peak respiratory exhange ratio compared between patients with, and without advanced HF **Time Frame:** At time of screening **Description:** The ratio between metabolic production of CO2 and the uptake of O2 measured during cardiopulmonary exercise test **Measure:** Minute ventilation-to-carbon dioxide output slope (VE/VCO2) compared between patients with, and without advanced HF **Time Frame:** At time of screening **Description:** The Borg scale score is a rating of perceived exertion on a scale from 6-20, with 6 representing at rest, and 20 the most strenuous exercise imaginable. Measured during cardiopulmonary exercise test **Measure:** Peak Borg scale score compared between patients with, and without advanced HF **Time Frame:** At time of screening **Measure:** 6 minute walk test compared between patients with, and without advanced HF **Time Frame:** At screening **Measure:** Quality of Life (Kansas City Cardiomyopathy Questionnaire (KCCQ) **Time Frame:** At screening **Measure:** NT-proBNP compared between patients with, and without advanced HF **Time Frame:** At screening ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. History of Chronic heart failure \> 3 months 2. Stable (no hospitalization last 3 months) NYHA functional class II-III 3. HFrEF patients (Left ventricular ejection fraction (LVEF) ≤ 30%) 4. On or attempted betablocker and Renin-Angiotensin System (RAS) inhibitor treatment 5. Informed consent Exclusion Criteria: 1. Body Mass Index (BMI) \> 40 kg/m2 2. Chronic renal replacement therapy or estimated Glomerular Filtration Rate (eGFR) \< 15 ml/min/1.73m2 3. Cardiac Resynchronization Therapy (CRT) implantation \< 3 months ago or planned CRT 4. Severe primary valvular disease 5. On waiting list for heart transplantation or referred for evaluation 6. Cancer or other severe non-cardiac disease with estimated life expectancy less than 1 year **Maximum Age:** 74 Years **Minimum Age:** 19 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients followed in Danish HF clinics in the Copenhagen region. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Finn Gustafsson, MD, PhD, DMSci **Phone:** +45 35459743 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Johan Larsson, MD **Phone:** +45 50298907 **Role:** CONTACT #### Locations **Location 1:** **City:** Copenhagen **Contacts:** ***Contact 1:*** - **Name:** Olav Wendelbo Nielsen, MD, ph.d, dr.med. - **Role:** CONTACT **Country:** Denmark **Facility:** Bispebjerg-Frederiksberg Hospital **Status:** NOT_YET_RECRUITING **Zip:** 2400 **Location 2:** **City:** Copenhagen **Contacts:** ***Contact 1:*** - **Name:** Morten Petersen, MD, ph.d - **Role:** CONTACT **Country:** Denmark **Facility:** Amager/Hvidovre Hospital **Status:** NOT_YET_RECRUITING **Zip:** 2650 **Location 3:** **City:** Copenhagen **Contacts:** ***Contact 1:*** - **Name:** Morten Schou, MD, ph.d - **Role:** CONTACT **Country:** Denmark **Facility:** Herlev and Gentofte Hospital **Status:** NOT_YET_RECRUITING **Zip:** 2730 **Location 4:** **City:** Glostrup **Contacts:** ***Contact 1:*** - **Name:** Anders Barasa, MD, ph.d - **Role:** CONTACT **Country:** Denmark **Facility:** Glostrup Hospital **Status:** RECRUITING **Zip:** 2600 **Location 5:** **City:** Hillerød **Contacts:** ***Contact 1:*** - **Name:** Nis Stride, MD, ph.d - **Role:** CONTACT **Country:** Denmark **Facility:** Nordsjællands Hospital Hillerød **Status:** NOT_YET_RECRUITING **Zip:** 3400 **Location 6:** **City:** Roskilde **Contacts:** ***Contact 1:*** - **Name:** Nadia Dridi - **Role:** CONTACT **Country:** Denmark **Facility:** Zeeland University Hospital Roskilde **Status:** NOT_YET_RECRUITING **Zip:** 4000 #### Overall Officials **Official 1:** **Affiliation:** Rigshospitalet, Denmark **Name:** Finn Gustafsson, MD, PhD, DMSci **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Crespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, Filippatos G, Gustafsson F, Tsui S, Barge-Caballero E, De Jonge N, Frigerio M, Hamdan R, Hasin T, Hulsmann M, Nalbantgil S, Potena L, Bauersachs J, Gkouziouta A, Ruhparwar A, Ristic AD, Straburzynska-Migaj E, McDonagh T, Seferovic P, Ruschitzka F. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018 Nov;20(11):1505-1535. doi: 10.1002/ejhf.1236. Epub 2018 Jul 17. **PMID:** 29806100 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02607579 **Brief Title:** Comparing Exparel & Ropivacaine for Pain Relief in Total Knee Arthroplasty **Official Title:** A Randomized, Blinded Study to Compare Exparel and Ropivacaine for Pain Relief Following Total Knee Arthroplasty #### Organization Study ID Info **ID:** 14-045 #### Organization **Class:** OTHER **Full Name:** Monmouth Medical Center ### Status Module #### Completion Date **Date:** 2017-07 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2017-04-27 **Type:** ACTUAL **Last Update Submit Date:** 2017-04-26 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2016-06 **Type:** ACTUAL #### Start Date **Date:** 2015-01 **Status Verified Date:** 2017-04 #### Study First Post Date **Date:** 2015-11-18 **Type:** ESTIMATED **Study First Submit Date:** 2015-07-27 **Study First Submit QC Date:** 2015-11-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Monmouth Medical Center #### Responsible Party **Investigator Affiliation:** Monmouth Medical Center **Investigator Full Name:** Ryan Plyler **Investigator Title:** Orthopaedic Surgeon/ Researcher **Type:** PRINCIPAL_INVESTIGATOR ### Description Module **Brief Summary:** The purpose of this prospective study is to examine the effect of two local anesthetics used in adductor canal blocks, with relation to pain, analgesic consumption, mobility, and pain related interference with activities and hospital length of stay. The two agents are bupivacaine and ropivacaine. The purpose of this trial is to examine the effect of these drugs being used in adductor canal blocks for pain relief, analgesic consumption, mobility, and pain related interference with activities and hospital length of stay. **Detailed Description:** Total knee arthroplasty (TKA) is associated with intense early postoperative pain. Effective pain management following total knee arthroplasty is imperative to facilitate early ambulation, mobilization and rehabilitation. The postoperative pain regimen should enhance functional recovery in addition to providing efficient analgesia with minimal side effects. To manage postoperative pain effectively, multimodal analgesia including acetaminophen, Toradol, Solu-Medrol, opioids and local anesthetics are used. Periarticular infiltration performed intra-operatively combined with ultrasound guided adductor-canal peripheral nerve blocks are effective in reducing pain following a TKA without causing quadriceps motor block which can impede mobilization. There are no published trials that the investigators could find to date, comparing adductor canal block with a single dose Exparel and adductor canal block with standard ropivacaine. A liposome is a manufactured spherical lipid vesicle that can be used to slowly release a drug thereby extending its duration of action. Exparel is such a compound that slowly releases bupivacaine. Local anesthetics block the conduction of all excitable tissue in a dose related fashion. The first tissues that are affected are nerves, which make these drugs of choice in neural block. Their local adverse effects include neurovascular manifestations are prolonged numbness, tingling, feeling of "pins and needles" or strange sensations. These effects are reversed with time. There are no additional potential risks or adverse effects due to the procedures or drugs being administered. The procedure is well established and the local anesthetics have a history of long term use in humans. ### Conditions Module **Conditions:** - Knee Osteoarthritis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This group is given an adductor canal block with Ropivacaine which is the previous gold standard medication. **Intervention Names:** - Drug: Ropivacaine **Label:** Ropivacaine **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** This group is given an adductor canal block with Exparel which is believed to last longer and provide a better pain relief post-operatively. **Intervention Names:** - Drug: Exparel **Label:** Exparel **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Exparel **Name:** Exparel **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Ropivacaine **Name:** Ropivacaine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The investigators will monitor patient pain scores every 6 hours during the hospital stay based on the Defense and Veterans Pain Rating Scale (DVPRS). **Measure:** Pain relief **Time Frame:** Hospital course (approximately 2-3 days) #### Secondary Outcomes **Description:** The investigators will compare the length of stay between the two groups. **Measure:** Length of stay **Time Frame:** Hospital course (approximately 2-3 days) **Description:** The investigators will compare the range of motion between the two groups during the participants' hospital course as measured by the physical therapists on a daily basis. **Measure:** Post-Operative Range of Motion **Time Frame:** Hospital course (approximately 2-3 days) **Description:** The investigators will compare the distance walked between the two groups during the participants' hospital course as measured by the physical therapists on a daily basis. **Measure:** Post-Operative Distance Walked **Time Frame:** Hospital course (approximately 2-3 days) **Description:** The investigators will monitor the amount of medication taken by participants during the hospital stay. **Measure:** Amount of Narcotics required **Time Frame:** Hospital course (approximately 2-3 days) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age 18 and up undergoing a total knee replacement with single surgeon. American Society of Anesthesiologists Physical Status Classification Scale (ASA) 1-3. Exclusion Criteria: * Allergy to local anesthestic, pre-existing peripheral neuropathy, revision surgery **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Long Branch **Country:** United States **Facility:** Monmouth Medical Center **State:** New Jersey **Zip:** 07740 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M12926 - Name: Osteoarthritis - Relevance: HIGH - As Found: Osteoarthritis - ID: M22168 - Name: Osteoarthritis, Knee - Relevance: HIGH - As Found: Knee Osteoarthritis - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010003 - Term: Osteoarthritis - ID: D000020370 - Term: Osteoarthritis, Knee ### Intervention Browse Module - Ancestors - ID: D000000779 - Term: Anesthetics, Local - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1700 - Name: Ropivacaine - Relevance: HIGH - As Found: Eye - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077212 - Term: Ropivacaine ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03336879 **Brief Title:** Repetitive Transcranial Magnetic Stimulation in Gambling Disorder **Official Title:** Exploring the Potential of High-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat Gambling Disorder (GD) #### Organization Study ID Info **ID:** v.2_19/10/2017 #### Organization **Class:** OTHER **Full Name:** ITAB - Institute for Advanced Biomedical Technologies ### Status Module #### Completion Date **Date:** 2020-12-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2017-11-08 **Type:** ACTUAL **Last Update Submit Date:** 2017-11-06 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-12-30 **Type:** ESTIMATED #### Start Date **Date:** 2017-11-01 **Type:** ACTUAL **Status Verified Date:** 2017-11 #### Study First Post Date **Date:** 2017-11-08 **Type:** ACTUAL **Study First Submit Date:** 2017-11-06 **Study First Submit QC Date:** 2017-11-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** ITAB - Institute for Advanced Biomedical Technologies #### Responsible Party **Investigator Affiliation:** ITAB - Institute for Advanced Biomedical Technologies **Investigator Full Name:** Giovanni Martinotti **Investigator Title:** Researcher **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Background: An imbalance between prefrontal cortex (PFC) and the mesolimbic reward system has been suggested to contribute to GD. GD patients showed increased functional connectivity between regions of the PFC and mesolimbic reward system, as well as reduced connectivity in the area of the PFC. The altered interaction between prefrontal structures and the mesolimbic reward system in GD shares similarity with functional organization reported in Substances Use Disorders (SUDs), suggesting a more general pathophysiology for addictive disorders Objectives: To test if rTMS can reduce craving and playing in Gambling Disorder, and also affect several mood, behavioral and cognitive alterations associated with prolonged Gambling Disorder. Eligibility: Healthy, right-handed adults ages 18-65 who do have Gambling Disorder. Design: This is a non-randomized, open label study. The study includes three phases: 1) a rTMS continued treatment phase; 2) a rTMS follow-up; and 3) a no rTMS follow-up. Prior to participating, participants will be screened with: * Questionnaires * Cognitive tests * Medical history * Physical exam After being enrolled, baseline behavioral and imaging data will be collected. In particular, participants will undergo: * Questionnaires * Cognitive tests During the continued rTMS phase, participants with Gambling Disorder will receive real rTMS. Repetitive TMS will be delivered during 10 outpatient treatment days, over 2 weeks (5 days/week). Following this phase, subjects will have 12 follow-up visits (once/weekly), during which they will receive rTMS, and behavioral assessments will be performed. At the end of the rTMS follow up period, participants will further receive 3 follow up visits (once a month), during which rTMS will not be performed, but behavioral data will be collected. Treatment includes: * rTMS: A coil is placed on the head. Brief electrical current passes through the coil. At each visit, participants will receive two rTMS sessions, with a 1hr interval between sessions. At the beginning of each rTMS session, they view gambling-related images for few minutes. * Repeat of screening tests and questionnaires **Detailed Description:** Gambling Disorder (GD) is a complex addictive disorder involving fronto-striatal connectivity and prefrontal top-down control modulation of reward-related brain areas. Repetitive transcranial magnetic stimulation (rTMS) seems to reduce cravings and improve cognitive function in substance dependent individuals. Moreover, rTMS has been shown to modulate dopaminergic and glutamatergic transmission, both involved in GD pathophysiology. However, the efficacy of rTMS in treating GD has not been evaluated and also, we lack a full characterization of rTMS effects on other important aspects, including effects on mood, cognition and changes in brain function. The purpose of this study is to investigate the effects of repetitive Transcranial Magnetic Stimulation (rTMS) at 15 Hz frequency on the left dorsolateral prefrontal cortex in patients affected by GD and to examine possible changes in mood, cognition, and brain activity and functional connectivity associated with this intervention. For this purpose, the investigators will recruit GD patients. After screening and informed consent, participants will undergo active rTMS for two consecutive weeks (twice a day) during the continued treatment phase, and a maintenance intervention (twice a week for 3 months), during the rTMS follow-up phase. Following this phase, participants will be followed for further 3 months, during which no rTMS will be delivered but clinical data will be collected. Procedure: The project consists of: Screening Visit (baseline), Phase 1 (continued treatment phase), Phase 2 (3 months- rTMS follow-up), Phase 3 (3 months follow-up without rTMS). First, there will be a screening visit, where a clinical interview will be conducted and questionnaires and tests will be administered to identify study participants who meet the inclusion and exclusion criteria. Baseline clinical and cognitive data will be acquired. In Phase 1, participants will receive 2 sessions of rTMS (active), twice per day for 10 consecutive days, for a total of 20 rTMS sessions. Following this, the investigators will evaluate the acute effect of treatment on relapse rate, gambling severity and craving, mood and cognition. In Phase 2 of the study, all participants will continue the treatment arm with rTMS (15Hz) for three months. Participants will receive 2 sessions of rTMS (active) once per week; clinical and cognitive data will be acquired once per month. The investigators will evaluate the acute effect of treatment on relapse rate, gambling severity and craving, mood and cognition. In Phase 3 of the study, participants will not receive any rTMS session. Clinical and cognitive data will be acquired once per month for three months. The investigators will evaluate the long-term effect of treatment on relapse rate, gambling severity and craving, mood and cognition. ### Conditions Module **Conditions:** - Gambling Disorder **Keywords:** - Gambling Disorder - Mental Disorder - Behavioral Addiction ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** non-randomized, open label study ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 10 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The intervention will be Repetitive Transcranial Magnetic Stimulation. Each patient will receive active stimulation targeting the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 15 Hz and 100% of the individual resting motor threshold, for a total of 40 trains (60 stimuli per train, inter-train interval of 15 second, total duration 13 minutes). Each session will be repeated twice/daily for 10 consecutive days for 2 weeks, during the continued treatment phase. Following this, the participants will receive the maintenance intervention of 2 sessions per week for 3 months (rTMS follow-up), at the same parameters described above. Device: MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark). **Intervention Names:** - Device: Repetitive Transcranial Magnetic Stimulation **Label:** Active rTMS (15 Hz) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Active rTMS (15 Hz) **Description:** Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique. The investigators will use a MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark). **Name:** Repetitive Transcranial Magnetic Stimulation **Other Names:** - rTMS **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** A Visual Analogue Scale (VAS) is an instrument to measure a characteristic or attitude that is believed to range across a continuum of values. The VAS is a horizontal line, 100 mm in length, anchored by word descriptors at each end (0 = lower scores; 10 = higher scores). The patient marks on the line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimeters from the left-hand end of the line to the point that the patient marks. **Measure:** Changes in the Visual Analogue Scale for Craving (VAS-craving) **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months **Description:** The Pathological Gambling Adaptation of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS) is a 10-item clinician-administered questionnaire that measures the severity of PG over the past one week. Scores from 0 (min) to 4 (max) are assigned according to the severity. The first set of questions (questions 1-5) assess urges and thoughts associated with pathological gambling, whereas the last five questions assess the behavioral component of the disorder. Both single set scores and total score will be calculated. **Measure:** Changes in the Pathological Gambling Adaptation of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS) **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months **Description:** Gambling behavior will be assessed using the TimeLine Follow Back (TLFB). TLFB is an interview-based assessment. Using a calendar, participants are guided through the process of recalling and reporting daily gambling behavior. TLFB provides measures of gambling episodes per week, gambling days per week, heavy gambling days per week. **Measure:** Changes in Gambling Disorder Severity as assessed by Timeline Follow Back (TLFB) **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months **Description:** Gambling Symptom Assessment Scale (G-SAS) is a 12-item self-rated scale designed to assess gambling symptom severity and change during treatment. Each 12-item scale has a score ranging from 0 - 4 (adjective anchors for 0 and 4 vary for each item). All items ask for an average symptom based on the past 7 days. Total score ranges from 0 (min) to 48 (max), higher scores indicate higher severity levels. **Measure:** Changes in Gambling Behavior as assessed by Gambling Symptom Assessment Scale (G-SAS) Total Score **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months #### Secondary Outcomes **Description:** The Iowa Gambling Task is a computerized card game commonly used to measure risky decision-making tendencies and sensitivity to reward and loss. Performance is calculated on the total net score results from the subtraction of the disadvantageous deck choices from the advantageous deck choices during the entire test (\[C'+D'\]-\[A'+B'\]). **Measure:** Changes in the Iowa Gambling Task (IGT) Performance **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months **Description:** The Snaith Hamilton Pleasure Scale (SHAPS) is a 14-item self-report scale designed to measure hedonic-tone/anhedonia. Each item is scored on a 4-point scale, ranging from 0 (not at all) to 3 (extremely). Sum the scores from all 14 parameters gives the SHAPS Total Score which may range from 0 (min) to 42 (max). **Measure:** Changes in Snaith Hamilton Pleasure Scale (SHAPS) Total Score **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months **Description:** The Temporal experience of Pleasure Scale (TEPS) is a 18-item self-report scale designed to evaluate individual trait dispositions in anticipatory and consummatory pleasure experiences. Each item is scored on a 6-point scale, ranging from 1 (extremely false) to 6 (extremely true). Sum the scores from all 20 parameters gives the TEPS Total Score which may range from 20 (min) to 108 (max). **Measure:** Changes in Temporal experience of Pleasure Scale (TEPS) Total **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months **Description:** The MADRS is a 10-item scale that evaluates the core symptoms and cognitive features of clinical depression. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. **Measure:** Changes in Montgomery-Asberg Depression Scale (MADRS) Total **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months] **Description:** The HAM-A is a 14-item scale that assesses anxiety symptoms of anxiety such as "anxious mood", "tension" or "fears". Each item is scored on a 5-point scale, ranging from 0 (not present) to 4 (severe). Sum the scores from all 14 parameters gives the HAM-A Total Score which may range from 0 (min) to 56 (max). **Measure:** Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months **Description:** The profile of mood state (POMS) is a questionnaire designed to measure present mood state by a list of adjectives on a 5-point Likert scale (0 = not at all; 4 = Extremely) and measures six dimensions of affect, including tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment. The measure has been shown to produce reliable and valid profiles of mood state. A Total Mood Disturbance Score may be calculated by adding the scores for Tension, Depression, Anger, Fatigue and Confusion and then subtracting the score for Vigor. **Measure:** Changes in Profile of Mood States (POMS), Total Mood Disturbance Score **Time Frame:** Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age 18 - 65; * Current diagnosis of Gambling Disorder, based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5); * Drug-free. Exclusion Criteria: * Current DSM-V diagnosis of substance use disorders other than nicotine dependence; * Current DSM-V diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder; * Use in the past 4 weeks of any medication with known pro-convulsant action; or current regular use of any psychotropic medications (benzodiazepines, antipsychotic medications, tricyclic antidepressants, anti-epileptics, mood stabilizers); * Any history of any clinically significant neurological disorder, including organic brain disease, epilepsy, stroke, brain lesions, multiple sclerosis, previous neurosurgery, or personal history of head trauma that resulted in loss of consciousness for \> 5 minutes and retrograde amnesia for \> 30 minutes; * Any personal or family history (1st degree relatives) of seizures other than febrile childhood seizures; * Any psychiatric, medical or social condition whether or not listed above, due to which, in the judgment of the PI and after any consults if indicated, participation in the study is not in the best interest of the patient; * For female patients: Pregnancy/breastfeeding. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Giovanni Martinotti, MD, PhD **Phone:** 0039 0871 3556914 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Mauro Pettorruso, MD **Phone:** 0039 3391979487 **Role:** CONTACT #### Locations **Location 1:** **City:** Chieti **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Givoanni Martinotti, MD, PhD - **Phone:** 0039 335 5627362 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Chiara Montemitro, MD - **Phone:** 0039 3281264713 - **Role:** CONTACT ***Contact 3:*** - **Name:** Massimo di Giannantonio, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Giovanni Martinotti, MD, PhD - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Chiara Montemitro, MD - **Role:** SUB_INVESTIGATOR **Country:** Italy **Facility:** Department of Neuroscience, Imaging and Clinical Sciences **Status:** RECRUITING **Zip:** 66100 **Location 2:** **City:** Roma **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mauro Pettorruso, MD - **Phone:** 039 339 1979487 - **Role:** CONTACT ***Contact 2:*** - **Name:** Mauro Pettorruso, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Fabrizio Fanella, MD - **Role:** SUB_INVESTIGATOR **Country:** Italy **Facility:** La Promessa ONLUS **Status:** NOT_YET_RECRUITING **Zip:** 00192 #### Overall Officials **Official 1:** **Affiliation:** Department of Neuroscience, Imaging and Clinical Sciences (ITAB) - University G. d'Annunzio - Chieti (Italy) **Name:** Massimo di Giannantonio, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Pettorruso M, Martinotti G, Montemitro C, De Risio L, Spagnolo PA, Gallimberti L, Fanella F, Bonci A, Di Giannantonio M; Brainswitch Study Group. Multiple Sessions of High-Frequency Repetitive Transcranial Magnetic Stimulation as a Potential Treatment for Gambling Addiction: A 3-Month, Feasibility Study. Eur Addict Res. 2020;26(1):52-56. doi: 10.1159/000504169. Epub 2019 Oct 30. **PMID:** 31665732 ## Document Section ### Large Document Module #### Large Docs - Date: 2017-10-19 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 354703 - Type Abbrev: Prot_SAP - Upload Date: 2017-11-06T10:57 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007174 - Term: Disruptive, Impulse Control, and Conduct Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M19100 - Name: Behavior, Addictive - Relevance: LOW - As Found: Unknown - ID: M8832 - Name: Gambling - Relevance: HIGH - As Found: Gambling - ID: M21827 - Name: Conduct Disorder - Relevance: LOW - As Found: Unknown - ID: M10219 - Name: Disruptive, Impulse Control, and Conduct Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005715 - Term: Gambling ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01063179 **Brief Title:** Velcade, Melphalan, Prednisone And Thalidomide Versus Velcade, Melphalan, Prednisone in Multiple Myeloma Patients **Official Title:** A PHASE III, MULTI-CENTER, RANDOMIZED OPEN LABEL STUDY OF VELCADE, MELPHALAN, PREDNISONE AND THALIDOMIDE (V-MPT) Versus VELCADE, MELPHALAN, PREDNISONE (V-MP) IN ELDERLY UNTREATED MULTIPLE MYELOMA PATIENTS #### Organization Study ID Info **ID:** GIMEMA-MM-03-05 #### Organization **Class:** OTHER **Full Name:** Fondazione EMN Italy Onlus #### Secondary ID Infos **ID:** 2005-004745-33 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-29 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Start Date **Date:** 2006-05 **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2010-02-05 **Type:** ESTIMATED **Study First Submit Date:** 2010-02-04 **Study First Submit QC Date:** 2010-02-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Fondazione EMN Italy Onlus #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The proposed study will evaluate whether the combination of VELCADE, Thalidomide , Melphalan and Prednisone (V-MPT), as induction treatment for newly diagnosed elderly MM patients, improves outcomes compared to the combination VELCADE-MP. **Detailed Description:** This phase III study represents a prospective randomized open label multicenter trial to evaluate whether the combination of VELCADE, Melphalan, Prednisone and Thalidomide (V-MPT), as induction treatment for newly diagnosed elderly MM patients, improves outcomes compared to the combination VELCADE-MP. Subjects will be randomized in a 1:1 allocation between: Arm A: 250 patients: V-MPT treatment Arm B: 250 patients: V-MP treatment Patients excluded from randomization are to be registered in Arm C. Patients randomized in arm A (Thalidomide based) will be further enrolled in the sub-study about the DVT prophylaxis. Patients will be evaluated at scheduled visits in up to 3 study periods: pre-treatment, treatment and long-term follow-up (LTFU). 1. Pre-treatment period: Screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility After registration subjects will be randomized. 2. Treatment period: Subjects in Arm A will receive: 1. Induction therapy: nine 5-week courses of VELCADE/Melphalan/Prednisone/Thalidomide (V-MPT) 2. Maintenance therapy: Thalidomide in combination with VELCADE Subjects in Arm B will receive: 1. Induction therapy: nine 5-week courses of VELCADE/Melphalan/Prednisone (V-MP) 2. No maintenance therapy is scheduled At the end of induction treatment or at the time of discontinuation of all study drugs, all patients are to attend study center visits on an every 6 to 8-week basis, until development of confirmed Progressive Disease (PD) 3. LTFU period: After development of confirmed PD all patients are to be followed for survival every 3 months via telephone or office visit. ### Conditions Module **Conditions:** - Multiple Myeloma **Keywords:** - Elderly patients - Bortezomib - Thalidomide ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 511 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Induction therapy with nine 5-week courses of VELCADE/Melphalan/Prednisone/Thalidomide (V-MPT) followed by maintenance therapy with Thalidomide and VELCADE **Intervention Names:** - Drug: Bortezomib, Melphalan, Prednisone, Thalidomide **Label:** Arm A: VMPT **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Induction therapy with nine 5-week courses of either VELCADE/Melphalan/Prednisone (V-MP). No maintenance is scheduled. **Intervention Names:** - Drug: Bortezomib, Melphalan, Prednisone **Label:** VMP **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm A: VMPT **Description:** Induction therapy: 9 courses with weekly VELCADE (4 doses) in combination with oral Melphalan 9 mg/m2,oral Prednisone 60 mg/m2 once daily on Days 1 to 4 of each course and Thalidomide 50 mg/day continuously. The dose of VELCADE is 1.3 mg/m2 administered as a bolus IV injection, on days 1, 8, 15, 22. Maintenance therapy: Thalidomide 50 mg/day continuously in combination with VELCADE 1.3 mg or maximum dose tolerated/m2/2 weeks. The maintenance will be initiated at the end of the 9th course and will be stopped after progression. The median expected duration of the maintenance treatment is approximately 2 years. **Name:** Bortezomib, Melphalan, Prednisone, Thalidomide **Other Names:** - Bortezomib - Velcade - Thalidomide **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - VMP **Description:** Induction therapy: 9 courses with weekly VELCADE(4 doses) in combination with oral Melphalan 9 mg/m2 and oral Prednisone 60 mg/m2 once daily on Days 1 to 4 of each course. No maintenance therapy is scheduled **Name:** Bortezomib, Melphalan, Prednisone **Other Names:** - Boirtezomib - velcade **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Determine whether the V-MPT combination improves progression free survival (PFS) **Time Frame:** Approximately 24 months #### Secondary Outcomes **Measure:** Determine whether the VMPT combination improves:Response rate, Overall Survival rate, Time and duration of response, Assess the safety, Assess the prognostic factors **Time Frame:** Approximately 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age \> 65 year old and not a candidate for stem cell transplant, or younger who refuses or is not eligible for high-dose therapy * Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage * Presence of measurable disease * Karnofsky performance status (PS) \> 60% * Able to read and complete the HRQOL instruments * Agrees to use an acceptable barrier method for contraception for the duration of the study * Pretreatment clinical laboratory values within 14 days of randomization: platelet count ≥ 100x109/L * hemoglobin ≥ 8 g/dL * absolute neutrophil count (ANC) ≥ 1.0x109/L * AST ≤ 2.5 times the upper limit of normal * ALT ≤ 2.5 times the upper limit of normal * total bilirubin ≤ 1.5 times the upper limit of normal * serum creatinine ≤ 2.5mg/dL * corrected serum calcium \<14 mg/dL (\<3.5 mmol/L) * Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. * Women of child-bearing potential must agree to use 2 methods of contraception: 1 effective (for example hormonal or tubal ligation) and 1 barrier (for example latex condom, diaphragm) for at least 4 weeks before starting the therapy, during the Treatment Period, and for 4 weeks after the last dose; * Males must agree to use barrier contraception (latex condoms) when engaging in reproductive activity during the Treatment Period and for 4 weeks after the last dose. Exclusion Criteria: * Diagnosis of smoldering multiple myeloma or MGUS. * Diagnosis of Waldenstrom's disease * Prior or current systemic therapy for multiple myeloma including steroids (with exception of emergency use of a short course \[maximum 4 days\] of steroids before randomization or prior or current use of biphosphonates) * Radiation therapy within 30 days before randomization * Plasmapheresis within 30 days before randomization * Major surgery within 30 days before randomization (Kyphoplasty is not considered major surgery) * History of allergic reaction attributable to compounds containing boron or mannitol, or to Thalidomide * Peripheral neuropathy Grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 3.0 * Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis * Other malignancy within the past 5 years. Exceptions: basal cell or non metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or FIGO Stage 1 carcinoma of the cervix * Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes, pulmonary disease) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study * Use of any investigational drugs within 30 days before randomization. * Pregnant or lactating women. A serum β-hCG pregnancy test must be performed at the Screening visit, for female patients of child-bearing potential. If the test is positive, the patient must be excluded from the study. Confirmation that the patient is not pregnant must be established by a negative serum or urinary pregnancy test with the result obtained 1 day prior to the Baseline visit (or the day of the visit if results are available before drug delivery). **Maximum Age:** 100 Years **Minimum Age:** 65 Years **Sex:** ALL **Standard Ages:** - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Torino **Country:** Italy **Facility:** A.O.U. S. Giovanni Battista **Zip:** 10126 #### Overall Officials **Official 1:** **Affiliation:** Divisione di Ematologia dell'Università di Torino, A.O.U. S. Giovanni Battista, Torino;Italy **Name:** Mario Boccadoro, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Larocca A, Mina R, Offidani M, Liberati AM, Ledda A, Patriarca F, Evangelista A, Spada S, Benevolo G, Oddolo D, Innao V, Cangiolosi C, Bernardini A, Musto P, Amico V, Fraticelli V, Paris L, Giuliani N, Falcone AP, Zambello R, De Paoli L, Romano A, Palumbo A, Montefusco V, Hajek R, Boccadoro M, Bringhen S. First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients: a pooled analysis of two randomized trials. Haematologica. 2020 Apr;105(4):1074-1080. doi: 10.3324/haematol.2019.220657. Epub 2019 Jun 27. **PMID:** 31248973 **Citation:** Montefusco V, Gay F, Spada S, De Paoli L, Di Raimondo F, Ribolla R, Musolino C, Patriarca F, Musto P, Galieni P, Ballanti S, Nozzoli C, Cascavilla N, Ben-Yehuda D, Nagler A, Hajek R, Offidani M, Liberati AM, Sonneveld P, Cavo M, Corradini P, Boccadoro M. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs. Haematologica. 2020 Jan;105(1):193-200. doi: 10.3324/haematol.2019.219139. Epub 2019 Jun 20. **PMID:** 31221778 **Citation:** Saltarella I, Morabito F, Giuliani N, Terragna C, Omede P, Palumbo A, Bringhen S, De Paoli L, Martino E, Larocca A, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Dammacco F, Boccadoro M, Vacca A, Ria R. Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial. J Hematol Oncol. 2019 Jan 9;12(1):4. doi: 10.1186/s13045-018-0691-4. **PMID:** 30626425 **Citation:** Cerrato C, Di Raimondo F, De Paoli L, Spada S, Patriarca F, Crippa C, Mina R, Guglielmelli T, Ben-Yehuda D, Oddolo D, Nozzoli C, Angelucci E, Cascavilla N, Rizzi R, Rocco S, Baldini L, Ponticelli E, Marcatti M, Cangialosi C, Caravita T, Benevolo G, Ria R, Nagler A, Musto P, Tacchetti P, Corradini P, Offidani M, Palumbo A, Petrucci MT, Boccadoro M, Gay F. Maintenance in myeloma patients achieving complete response after upfront therapy: a pooled analysis. J Cancer Res Clin Oncol. 2018 Jul;144(7):1357-1366. doi: 10.1007/s00432-018-2641-5. Epub 2018 Apr 19. **PMID:** 29675792 **Citation:** Caltagirone S, Ruggeri M, Aschero S, Gilestro M, Oddolo D, Gay F, Bringhen S, Musolino C, Baldini L, Musto P, Petrucci MT, Gaidano G, Passera R, Bruno B, Palumbo A, Boccadoro M, Omede P. Chromosome 1 abnormalities in elderly patients with newly diagnosed multiple myeloma treated with novel therapies. Haematologica. 2014 Oct;99(10):1611-7. doi: 10.3324/haematol.2014.103853. Epub 2014 Jul 11. **PMID:** 25015938 **Citation:** Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID, Grasso M, Franceschini L, Gottardi D, Zambello R, Montefusco V, Falcone AP, Omede P, Marasca R, Morabito F, Mina R, Guglielmelli T, Nozzoli C, Passera R, Gaidano G, Offidani M, Ria R, Petrucci MT, Musto P, Boccadoro M, Cavo M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol. 2014 Mar 1;32(7):634-40. doi: 10.1200/JCO.2013.52.0023. Epub 2014 Jan 21. **PMID:** 24449241 **Citation:** Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, Ria R, Offidani M, Patriarca F, Nozzoli C, Petrucci MT, Benevolo G, Vincelli I, Guglielmelli T, Grasso M, Marasca R, Baldini L, Montefusco V, Musto P, Cascavilla N, Majolino I, Musolino C, Cavo M, Boccadoro M, Palumbo A. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011 Nov 24;118(22):5759-66. doi: 10.1182/blood-2011-05-353995. Epub 2011 Sep 27. **PMID:** 21951682 **Citation:** Gay F, Larocca A, Wijermans P, Cavallo F, Rossi D, Schaafsma R, Genuardi M, Romano A, Liberati AM, Siniscalchi A, Petrucci MT, Nozzoli C, Patriarca F, Offidani M, Ria R, Omede P, Bruno B, Passera R, Musto P, Boccadoro M, Sonneveld P, Palumbo A. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood. 2011 Mar 17;117(11):3025-31. doi: 10.1182/blood-2010-09-307645. Epub 2011 Jan 12. **PMID:** 21228328 **Citation:** Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. doi: 10.1182/blood-2010-07-294983. Epub 2010 Aug 31. Erratum In: Blood. 2012 Dec 20;120(26):5250. **PMID:** 20807892 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000020141 - Term: Hemostatic Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010265 - Term: Paraproteinemias - ID: D000001796 - Term: Blood Protein Disorders - ID: D000006402 - Term: Hematologic Diseases - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12058 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: M27588 - Name: Neoplasms, Plasma Cell - Relevance: HIGH - As Found: Multiple Myeloma - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M13178 - Name: Paraproteinemias - Relevance: LOW - As Found: Unknown - ID: M5077 - Name: Blood Protein Disorders - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T3947 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma ### Condition Browse Module - Meshes - ID: D000009101 - Term: Multiple Myeloma - ID: D000054219 - Term: Neoplasms, Plasma Cell ### Intervention Browse Module - Ancestors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018931 - Term: Antineoplastic Agents, Hormonal - ID: D000000970 - Term: Antineoplastic Agents - ID: D000018906 - Term: Antineoplastic Agents, Alkylating - ID: D000000477 - Term: Alkylating Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000019653 - Term: Myeloablative Agonists - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000007917 - Term: Leprostatic Agents - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000006131 - Term: Growth Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M14121 - Name: Prednisone - Relevance: HIGH - As Found: Min - ID: M11541 - Name: Melphalan - Relevance: HIGH - As Found: Modified - ID: M376 - Name: Bortezomib - Relevance: HIGH - As Found: 14 days - ID: M16559 - Name: Thalidomide - Relevance: HIGH - As Found: List - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M20942 - Name: Antineoplastic Agents, Alkylating - Relevance: LOW - As Found: Unknown - ID: M3820 - Name: Alkylating Agents - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M22318 - Name: Angiogenesis Inhibitors - Relevance: LOW - As Found: Unknown - ID: M9231 - Name: Growth Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000013792 - Term: Thalidomide - ID: D000011241 - Term: Prednisone - ID: D000069286 - Term: Bortezomib - ID: D000008558 - Term: Melphalan ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04219579 **Brief Title:** Antithrombin III Concentrate After Liver Transplantation **Official Title:** Continuous Versus Intermittent Infusion of Human Antithrombin III Concentrate in the Immediate Postoperative Period After Liver Transplantation #### Organization Study ID Info **ID:** HGRyu_AT-III #### Organization **Class:** OTHER **Full Name:** Seoul National University Hospital ### Status Module #### Completion Date **Date:** 2022-06-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-01 **Type:** ACTUAL **Last Update Submit Date:** 2022-06-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-06-28 **Type:** ACTUAL #### Start Date **Date:** 2020-01-03 **Type:** ACTUAL **Status Verified Date:** 2022-06 #### Study First Post Date **Date:** 2020-01-07 **Type:** ACTUAL **Study First Submit Date:** 2019-12-29 **Study First Submit QC Date:** 2020-01-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Seoul National University Hospital #### Responsible Party **Investigator Affiliation:** Seoul National University Hospital **Investigator Full Name:** Ho Geol Ryu **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study was designed to demonstrate more effective administration method of AT-III in immediate post-liver transplantation period. **Detailed Description:** Antithrombin III(AT-III) concentrates have been used to prevent critical thrombosis in the immediate post-liver transplantation period without clear evidence regarding the optimal dose or administration scheme. The investigators retrospectively analyzed the clinical data from the patients who received liver transplantation and developed pharmacokinetic model of AT-III in the previous research. According to this study, optimal AT-III activity level will be well-maintained with smaller dose with continuous infusion than with intermittent infusion which is widely accepted way of administration currently. A prospective study was planned to show the more effective manner of AT-III concentrate administration after liver transplantation. ### Conditions Module **Conditions:** - Liver Transplant; Complications **Keywords:** - antithrombin III - liver transplantation - administration method - dosage ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 130 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Immediately after operation, 2000 international unit (IU) of Antithrombin-III (AT-III) concentrate is loaded for 1 hour. AT-III concentrate 3000 IU is continuously infused through following 71 hours. **Intervention Names:** - Drug: Antithrombin III, continuous infusion **Label:** Continuous infusion **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Every 6 hours, 500 IU of AT-III concentrate is infused through 1 hour during the first 72 hours after liver transplantation. **Intervention Names:** - Drug: Antithrombin III, Intermittent infusion **Label:** Intermittent infusion **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Continuous infusion **Description:** Antithrombin-III is administered continuously **Name:** Antithrombin III, continuous infusion **Other Names:** - Antithrombin III, human **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Intermittent infusion **Description:** Antithrombin-III is administered intermittently **Name:** Antithrombin III, Intermittent infusion **Other Names:** - Antithrombin III, human **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Proportion of patients whose AT-III activity level is within the target range (80-120%) **Measure:** Proportion of patients within target range at postoperative 72 hours **Time Frame:** 72 hours after liver transplantation #### Secondary Outcomes **Description:** Proportion of patients whose AT-III activity level is within the target range (80-120%) **Measure:** Proportion of patients within target range at postoperative 12/24/48/84 hours **Time Frame:** 12/24/48/84 hours after liver transplantation **Description:** Among the measured AT-III activity levels, proportion of the values within the target range (80-120%) **Measure:** Proportion of AT-III level values within target range **Time Frame:** 12/24/48/72/84 hours after liver transplantation **Description:** Time required for AT-III level value to fall within target range (80-120%, hours) **Measure:** Time required for AT-III level value to fall within target range **Time Frame:** operation day ~ postoperative day 7 **Description:** AT-III infusion is stopped for 24 hours when AT-III plasma activity level exceeds 120%, then restarted after the value is confirmed to be less than 120%. **Measure:** Duration for cessation of AT-III concentrate administration **Time Frame:** operation day ~ postoperative day 7 **Description:** Bleeding requiring intervention **Measure:** Bleeding requiring intervention **Time Frame:** operation day ~ postoperative day 7 **Description:** Hepatic artery thrombosis, portal vein thrombosis **Measure:** Thrombosis event **Time Frame:** operation day ~ postoperative day 7 **Description:** number of days from operation to discharge **Measure:** Postoperative hospital stay **Time Frame:** through the hospital day, an average of 14 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Scheduled operation * Living donor liver transplantation * Adult patients (\>=18 years old) Exclusion Criteria: * Patients under 18 years old * Emergency operation * Deceased donor liver transplantation **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Seoul National University Hospital **Zip:** 03080 #### Overall Officials **Official 1:** **Affiliation:** Seoul National University Hospital **Name:** Ho Geol Ryu, MD, PhD **Role:** STUDY_CHAIR ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000015842 - Term: Serine Proteinase Inhibitors - ID: D000011480 - Term: Protease Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000925 - Term: Anticoagulants ### Intervention Browse Module - Browse Branches - Abbrev: Hemat - Name: Hematinics - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M4307 - Name: Antithrombins - Relevance: HIGH - As Found: Cobalt - ID: M4306 - Name: Antithrombin III - Relevance: HIGH - As Found: Injectate - ID: M14343 - Name: Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M18391 - Name: Serine Proteinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M19609 - Name: HIV Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4244 - Name: Anticoagulants - Relevance: LOW - As Found: Unknown - ID: T18 - Name: Serine - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000000991 - Term: Antithrombins - ID: D000000990 - Term: Antithrombin III ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05461079 **Acronym:** Epigenetics **Brief Title:** Sperm Phenotype and Differentially Methylated Regions **Official Title:** Association Between Anogenital Distance, Sperm Phenotype and Epigenetics in Infertile Men. #### Organization Study ID Info **ID:** RME12072017 #### Organization **Class:** OTHER **Full Name:** University of Basel ### Status Module #### Completion Date **Date:** 2023-12-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-20 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-01-30 **Type:** ACTUAL #### Start Date **Date:** 2017-11-01 **Type:** ACTUAL **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2022-07-15 **Type:** ACTUAL **Study First Submit Date:** 2017-12-09 **Study First Submit QC Date:** 2022-07-12 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Geneva, Switzerland #### Lead Sponsor **Class:** OTHER **Name:** University of Basel #### Responsible Party **Investigator Affiliation:** University of Basel **Investigator Full Name:** Christian De Geyter **Investigator Title:** Prof. Dr.med. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Testicular dysgenesis syndrome (TDS) is known to cause epigenetic abnormalities in spermatozoa. Anogenital distance (AGD) is considered to be a suitable clinical marker of TDS, but the direct link between AGD and epigenetic abnormalities is still missing. Infertile men (n=10) presenting with shortened AGD and a control group of normal semen donors (n=10) with normal AGD will then be asked to provide one semen sample each. Using a flow cytometer and sorter (FACS) their spermatozoa will be sorted into populations of spermatozoa with/without DNA fragmentation or with/without chromatin decondensation. These sorted populations of spermatozoa will then be examined for differences in epigenetic imprinting differences using whole genome expression analysis. Whereas the sorting of spermatozoa will be carried out in Basel, the epigenetic analysis will be carried at the University of Geneva. **Detailed Description:** A subset of 10 men with shortened AGD (together with a control group of 10 fertile donors with normal AGD) will be asked to provide up to three semen samples, each of which then will be sorted with FACS into subpopulations with/without DNA fragmentation and into subpopulations with/without chromatin decondensation. Spermatozoa with fragmented DNA will be separated through FACS-sorting of spermatozoa with intact DNA using the YoPro 1-dye, which has been shown to correlate significantly with the degree of DNA fragmentation in the nuclei of sperm. In addition, spermatozoa with abnormal chromatin remodelling will be separated through sorting from spermatozoa with condensed chromatin using the fluorochrome chromomycin A3 (CMA3), which competes for protamin for binding to the minor groove of DNA thereby correlating with the persistence of histones in the sperm nuclei. Pilot experiments have demonstrated the highly significant and close correlation of CMA3 with anilin blue staining. Anilin blue staining is not suitable for the sorting experiment, because it requires fixation of the spermatozoa. Sorting based on CMA3 can be carried out with living spermatozoa. The sorted and anonymized samples will then be sent frozen in dry ice to a laboratory at the University of Geneva for the assessment of differences in the epigenetic imprinting of the DNA using whole genome expression studies. ### Conditions Module **Conditions:** - Infertility, Male ### Design Module #### Bio Spec **Description:** Spermatozoa sorted with FACS according to two different staining methods: YoPro1 (apoptosis) and CMA3 (histone content). After sorting, we obtained four different groups: 1. YoPro1 positive and 2. YoPro1 negative, CMA3 positive and CMA3 negative. All sorted samples were stored frozen and sent for analysis of whole genome methylation status. **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 10 infertile men with shortened AGD (\< 40 mm) **Intervention Names:** - Diagnostic Test: obtention of up to three semen samples **Label:** subfertile men #### Arm Group 2 **Description:** 10 fertile semen donors with normal AGD (\>40 mm) **Intervention Names:** - Diagnostic Test: obtention of up to three semen samples **Label:** fertile semen donors ### Interventions #### Intervention 1 **Arm Group Labels:** - fertile semen donors - subfertile men **Description:** sorting of spermatozoa with flow cytometry. In the presence of insufficient numbers of spermatozoa after sorting (\<15 mill), up to three semen samples will be collected. **Name:** obtention of up to three semen samples **Other Names:** - conventional semen analysis followed by sorting **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** number of differentially methylated transposable regulatory sequences in the genome of sorted spermatozoa. **Measure:** anogenital distance and epigenetics **Time Frame:** 6 months #### Secondary Outcomes **Description:** based on conventional semen analysis: concentration of spermatozoa (in mill/ml). **Measure:** sperm phenotype 1 **Time Frame:** 6 months **Description:** based on conventional semen analysis: progressive motility (in %). **Measure:** sperm phenotype 2 **Time Frame:** 6 months **Description:** based on conventional semen analysis: normal morphology (in %), staining). **Measure:** sperm phenotype 3 **Time Frame:** 6 months **Description:** chromatin decondensation (as given by % of CMA3 staining). **Measure:** sperm phenotype 4 **Time Frame:** 6 months **Description:** DNA fragmentation (% of YoPro 1-staining). **Measure:** sperm phenotype 5 **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * infertile men with known anogenital distance Exclusion Criteria: * sperm concentration must be more than 15 million/ml to allow appropriate sorting with flow cytometry... **Maximum Age:** 55 Years **Minimum Age:** 20 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** MALE **Standard Ages:** - ADULT **Study Population:** Both the 10 infertile men with shortened AGD and the fertile control men (semen donors) will be recruited and examined in the infertility consultation of the Clinic of Gyn. Endocrinology and Reproductive Medicine. ### Contacts Locations Module #### Locations **Location 1:** **City:** Basel **Country:** Switzerland **Facility:** Christian De Geyter **Zip:** 4031 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000005832 - Term: Genital Diseases, Male - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10290 - Name: Infertility - Relevance: HIGH - As Found: Infertility - ID: M10292 - Name: Infertility, Male - Relevance: HIGH - As Found: Infertility, Male - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007246 - Term: Infertility - ID: D000007248 - Term: Infertility, Male ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT06338579 **Acronym:** AutoMMaN **Brief Title:** Overview of Self-medication Among French Navy Personnel **Official Title:** Overview and Determinants of Self-medication Among Personnel Deployed on French Navy Surface Ships #### Organization Study ID Info **ID:** 2023PPRC04 #### Organization **Class:** OTHER **Full Name:** Direction Centrale du Service de Santé des Armées #### Secondary ID Infos **Domain:** IDRCB **ID:** 2023-A01763-42 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2026-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-28 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-03 **Type:** ESTIMATED #### Start Date **Date:** 2024-04 **Type:** ESTIMATED **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2024-03-29 **Type:** ACTUAL **Study First Submit Date:** 2024-03-21 **Study First Submit QC Date:** 2024-03-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Direction Centrale du Service de Santé des Armées #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The goal of this cross-sectional descriptive observational study is to assess the extent of self-medication among the crews of surface ships at the Toulon naval base. This study could include healthy volunteers, or participants with well-controlled chronic pathologies enabling them to be fit for embarkation, who are currently being deployed for at least 4 weeks on a surface ship at the naval base. Participants will tick and complete a questionnaire (between 15 and 30 minutes) after 4 consecutive weeks on the ship. ### Conditions Module **Conditions:** - Self Medication ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 800 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** A questionnaire is distributed and self-administered 4 weeks before the start of an embarked mission on a surface ship at the Toulon naval base, during an embarked mission of at least 4 weeks. The questionnaire consists of 2 parts: * A section on socio-demographic characteristics * A section on self-medication practices during this deployment **Name:** Questionnaire **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Percentage of patients who have self-medicated at least once since the start of their current mission, among respondents working on surface ships at the naval base on missions lasting more than 4 weeks (excluding malaria prophylaxis, contraception and treatment of a chronic pathology prescribed by a doctor) **Measure:** percentage of patients who have self-medication **Time Frame:** up to 4 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * French military personnel; * age \> 18; * embarked on a French navy vessel from the naval base; * for a minimum 4-week mission; * covered by social security. Exclusion Criteria: * Refusal to participate, * Legionnaire * Military Health Services member **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** healthy volunteers, or participants with well-controlled chronic pathologies enabling them to be fit for embarkation, military personnel currently deployed for at least 4 weeks on a naval base surface ship ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03474679 **Brief Title:** A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD) **Official Title:** A Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Subjects With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD) #### Organization Study ID Info **ID:** CR108443 #### Organization **Class:** INDUSTRY **Full Name:** Janssen Pharmaceutical K.K. #### Secondary ID Infos **Domain:** Janssen Pharmaceutical K.K., Japan **ID:** 54179060GVH3001 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2021-11-29 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-02-03 **Type:** ACTUAL **Last Update Submit Date:** 2023-01-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-11-29 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-02-03 **Type:** ACTUAL **Results First Submit Date:** 2022-11-27 **Results First Submit QC Date:** 2023-01-17 #### Start Date **Date:** 2018-05-01 **Type:** ACTUAL **Status Verified Date:** 2023-01 #### Study First Post Date **Date:** 2018-03-22 **Type:** ACTUAL **Study First Submit Date:** 2018-03-16 **Study First Submit QC Date:** 2018-03-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Janssen Pharmaceutical K.K. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate efficacy of ibrutinib in Japanese participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (complete response \[CR\] and partial response \[PR\] defined by National Institutes of Health \[NIH\] consensus development project criteria \[2014\]). ### Conditions Module **Conditions:** - Graft vs Host Disease ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 19 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive 420 milligram (mg) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation. **Intervention Names:** - Drug: Ibrutinib **Label:** Ibrutinib **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Ibrutinib **Description:** Participants will receive 420 mg (3 \* 140 mg capsules) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation. **Name:** Ibrutinib **Other Names:** - PCI-32765 - JNJ-54179060 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death based on the National Institutes of Health (NIH) Consensus Development Project Criteria (2014). CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and chronic graft versus host disease (cGVHD) progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. **Measure:** Overall Response Rate (ORR) **Time Frame:** Up to 3 year 6 months #### Secondary Outcomes **Description:** Sustained response rate was defined as percentage of participants with NIH defined CR or PR that was sustained for at least 20 weeks. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site. **Measure:** Sustained Response Rate **Time Frame:** Up to 3 year 6 months **Description:** DOR is defined as the duration from the date of initial response (CR or PR) to the date of progressive cGVHD or death, whichever occurred first. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. **Measure:** Duration of Response (DOR) **Time Frame:** Up to 3 year 6 months **Description:** cGVHD response rate was defined as percentage of participants with NIH defined CR or PR at each timepoint. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site. **Measure:** cGVHD Response Rate at Each Timepoints **Time Frame:** Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157 **Description:** Change in the amount of corticosteroid required over time was reported. **Measure:** Change in the Amount of Corticosteroid Required Over Time **Time Frame:** Baseline, Weeks 24, 48, 96, and 144 **Description:** Percentage of participants with overall improvement in Lee cGVHD symptom scale score was reported. Lee cGVHD symptom scale is a patient-reported symptom scale used to measure symptom burden and has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0-Not at all, 1-Slightly, 2-Moderately, 3-Quite a bit, 4-Extremely, with lower values representing a better outcome. A score was calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 with a higher score indicating worse symptoms. An overall score was calculated as the average of these 7 subscales if at least 4 subscales had valid scores. A change of greater than or equal to (\>=) 7 points on the Lee cGVHD symptom scale overall score was considered significant and relates to improvement in quality of life (QoL). **Measure:** Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score **Time Frame:** Up to 3 year 6 months **Description:** An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs are adverse events with onset during the treatment phase or that were a consequence of a preexisting condition that has worsened since baseline, and occurred during treatment or within 30 days following the last dose of study treatment, or any adverse event that was considered study treatment-related regardless of the start date of the event. **Measure:** Number of Participants With Treatment-emergent Adverse Events (TEAEs) **Time Frame:** Up to 3 year 6 months **Description:** AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of ibrutinib. **Measure:** Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of ibrutinib. **Measure:** Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib **Time Frame:** 0 to 24 hours (Day 1 of Weeks 1 and 2) **Description:** Cmax is defined as maximum observed plasma concentration of ibrutinib. **Measure:** Maximum Observed Plasma Concentration (Cmax) of Ibrutinib **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib. **Measure:** Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** T1/2 is defined as elimination half-life of ibrutinib. **Measure:** Elimination Half-Life (t1/2) of Ibrutinib **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** CL/F is defined as apparent clearance of ibrutinib. **Measure:** Apparent Clearance (CL/F) of Ibrutinib **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** Vd/F is defined as apparent volume of distribution of ibrutinib. **Measure:** Apparent Volume of Distribution (Vd/F) of Ibrutinib **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of ibrutinib. **Measure:** Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of PCI-45227. **Measure:** Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227 **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of PCI-45227. **Measure:** Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227 **Time Frame:** 0 to 24 hours (Day 1 of Weeks 1 and 2) **Description:** Cmax is defined as maximum observed plasma concentration of PCI-45227. **Measure:** Maximum Observed Plasma Concentration (Cmax) of PCI-45227 **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** Tmax is defined as time to reach the maximum observed plasma concentration of PCI-45227. **Measure:** Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227 **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** T1/2 is defined as elimination half-life of PCI-45227. **Measure:** Elimination Half-Life (t1/2) of PCI-45227 **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** CL/F is defined as apparent clearance of PCI-45227. **Measure:** Apparent Clearance (CL/F) of PCI-45227 **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** Vd/F is defined as apparent volume of distribution of PCI-45227. **Measure:** Apparent Volume of Distribution (Vd/F) of PCI-45227 **Time Frame:** Day 1 of Weeks 1 and 2 **Description:** AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of PCI-45227. **Measure:** Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227 **Time Frame:** Day 1 of Weeks 1 and 2 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Steroid dependent/refractory chronic graft versus host disease (cGVHD) defined as modified National Institutes of Health (NIH) criteria (2014) below at any time post-hematopoietic cell transplant (post-HCT): a) Dependent disease, defined as, when glucocorticoid (prednisolone doses greater than or equal to \[\>=\] 0.25 milligram per kilogram per day (mg/kg/day)or \>=0.5 milligram per kilogram (mg/kg) every other day) are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks. In case of inability to taper the dose to less than or equal to (\<=)0.25 mg/kg/day or \<=0.5 mg/kg every other day (prednisolone doses) due to recurrence or progression of cGVHD manifestations, it is considered as steroid-dependent disease if the lowest tapering dose of the second occasion is equal or higher than the lowest tapering dose of the first occasion; b) Refractory disease, defined as, when cGVHD manifestations progress despite the use of a regimen containing glucocorticoid (prednisolone at \>=1 mg/kg/day for at least 1 week) or persist without improvement despite continued treatment with glucocorticoid (prednisolone at \>=0.5 mg/kg/day or 1 mg/kg every other day) for at least 4 weeks * Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting ibrutinib * At the time of trial enrollment, participants may be receiving other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting ibrutinib * Clinically stable or worsening cGVHD for a minimum of 14 days between screening and Day 1 cGVHD response assessment * Karnofsky or Lansky (participants less than \[\<\]16 years) performance status \>=60 Exclusion Criteria: * Active acute graft versus host disease (GVHD) * More than 3 previous systemic treatments for cGVHD. Treatment with glucocorticoids is considered a treatment for cGVHD and should be included in determining the number of previous treatments * History of treatment with a tyrosine kinase inhibitor (example \[e.g.\] imatinib), purine analogs, or other cancer chemotherapy in the 4 weeks prior to starting ibrutinib. Participants may have received ibrutinib pre-transplant for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma * History of treatment with monoclonal T and B cell antibodies in the 8 weeks prior to starting ibrutinib * Vaccinated with live, attenuated vaccines within 4 weeks of first dose of ibrutinib **Minimum Age:** 12 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Anjo-shi **Country:** Japan **Facility:** Anjo Kosei Hospital **Zip:** 446-8602 **Location 2:** **City:** Bunkyo-ku **Country:** Japan **Facility:** Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital **Zip:** 113-8677 **Location 3:** **City:** Hiroshima **Country:** Japan **Facility:** Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital **Zip:** 730-8619 **Location 4:** **City:** Hyogo **Country:** Japan **Facility:** Kobe City Medical Center General Hospital **Zip:** 650-0047 **Location 5:** **City:** Isehara **Country:** Japan **Facility:** Tokai University Hospital **Zip:** 259-1193 **Location 6:** **City:** Izumi **Country:** Japan **Facility:** Osaka Women's and Children's Hospital **Zip:** 594-1101 **Location 7:** **City:** Kumamoto-shi **Country:** Japan **Facility:** National Hospital Organization Kumamoto Medical Center **Zip:** 860-0008 **Location 8:** **City:** Kurashiki **Country:** Japan **Facility:** Kurashiki Central Hospital **Zip:** 710-8602 **Location 9:** **City:** Maebashi **Country:** Japan **Facility:** Gunmaken Saiseikai Maebashi Hospital **Zip:** 371-0821 **Location 10:** **City:** Nagoya **Country:** Japan **Facility:** Japanese Red Cross Nagoya Daiichi Hospital **Zip:** 453-8511 **Location 11:** **City:** Nishinomiya **Country:** Japan **Facility:** The Hospital of Hyogo College of Medicine **Zip:** 663-8501 **Location 12:** **City:** Okayama **Country:** Japan **Facility:** Okayama University Hospital **Zip:** 700-8558 **Location 13:** **City:** Osaka **Country:** Japan **Facility:** Osaka City University Hospital **Zip:** 545-8586 **Location 14:** **City:** Sapporo-shi **Country:** Japan **Facility:** Hokkaido University Hospital **Zip:** 060-8648 **Location 15:** **City:** Setagaya-ku **Country:** Japan **Facility:** National Center for Child Health and Development **Zip:** 157-8535 #### Overall Officials **Official 1:** **Affiliation:** Janssen Pharmaceutical K.K. **Name:** Janssen Pharmaceutical K.K., Japan Clinical Trial **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Doki N, Toyosaki M, Shiratori S, Osumi T, Okada M, Kawakita T, Sawa M, Ishikawa T, Ueda Y, Yoshinari N, Nakahara S. An Open-Label, Single-Arm, Multicenter Study of Ibrutinib in Japanese Patients With Steroid-dependent/Refractory Chronic Graft-Versus-Host Disease. Transplant Cell Ther. 2021 Oct;27(10):867.e1-867.e9. doi: 10.1016/j.jtct.2021.05.019. Epub 2021 Jun 6. **PMID:** 34102349 ## Document Section ### Large Document Module #### Large Docs - Date: 2018-07-24 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 2580413 - Type Abbrev: Prot - Upload Date: 2022-11-27T23:39 - Date: 2022-01-13 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 956899 - Type Abbrev: SAP - Upload Date: 2022-11-27T23:39 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007154 - Term: Immune System Diseases - ID: D000092124 - Term: Organizing Pneumonia - ID: D000001989 - Term: Bronchiolitis Obliterans - ID: D000001988 - Term: Bronchiolitis - ID: D000001991 - Term: Bronchitis - ID: D000001982 - Term: Bronchial Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000008173 - Term: Lung Diseases, Obstructive - ID: D000008171 - Term: Lung Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M9189 - Name: Graft vs Host Disease - Relevance: HIGH - As Found: Graft vs Host Disease - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M5264 - Name: Bronchiolitis - Relevance: LOW - As Found: Unknown - ID: M2893 - Name: Bronchiolitis Obliterans Syndrome - Relevance: HIGH - As Found: Chronic Graft Versus Host Disease - ID: M5265 - Name: Bronchiolitis Obliterans - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M2894 - Name: Organizing Pneumonia - Relevance: LOW - As Found: Unknown - ID: M5267 - Name: Bronchitis - Relevance: LOW - As Found: Unknown - ID: M5258 - Name: Bronchial Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: HIGH - As Found: Chronic Graft Versus Host Disease - ID: T2832 - Name: Homologous Wasting Disease - Relevance: HIGH - As Found: Graft Versus Host Disease - ID: T871 - Name: Bronchiolitis Obliterans - Relevance: LOW - As Found: Unknown - ID: T872 - Name: Bronchiolitis Obliterans Organizing Pneumonia - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000092122 - Term: Bronchiolitis Obliterans Syndrome - ID: D000006086 - Term: Graft vs Host Disease ### Intervention Browse Module - Ancestors - ID: D000092004 - Term: Tyrosine Kinase Inhibitors - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M42179 - Name: Ibrutinib - Relevance: HIGH - As Found: Effective - ID: M2889 - Name: Tyrosine Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: T22 - Name: Tyrosine - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000551803 - Term: Ibrutinib ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2022-12-27 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** The safety analysis set included all enrolled participants who received at least 1 dose of study drug. #### Event Groups **Group ID:** EG000 **Title:** Ibrutinib 420 mg **Deaths Num Affected:** 7 **Deaths Num At Risk:** 19 **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** EG000 **Other Num Affected:** 19 **Other Num at Risk:** 19 **Serious Number Affected:** 12 **Serious Number At Risk:** 19 **Title:** Ibrutinib 420 mg **Frequency Threshold:** 5 #### Other Events **Term:** Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Immune Thrombocytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Increased Tendency to Bruise **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Iron Deficiency Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Leukopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Splenic Infarction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Cardiac Failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Cardiac Failure Chronic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypothyroidism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Cataract **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Conjunctival Erosion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Conjunctival Hyperaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Dry Eye **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Glaucoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Ocular Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Photophobia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Abdominal Pain Upper **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Ascites **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Cheilitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Dental Caries **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Diarrhoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Enterocolitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Gastric Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Gastric Mucosal Hypertrophy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Gastrointestinal Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Stomatitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Tooth Loss **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Generalised Oedema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Malaise **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Oedema Peripheral **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Physical Deconditioning **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hepatic Function Abnormal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Liver Disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Food Allergy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypogammaglobulinaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Seasonal Allergy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Appendiceal Abscess **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Bronchiolitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Cellulitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Conjunctivitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Cytomegalovirus Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Haematoma Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Herpes Zoster **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Impetigo **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Influenza **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Nasopharyngitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Oral Candidiasis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Otitis Externa **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Paronychia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pharyngitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pneumonia Aspiration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pneumonia Bacterial **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pneumonia Fungal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Postoperative Wound Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pseudomembranous Colitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pyelonephritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Sinusitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Upper Respiratory Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Anaemia Postoperative **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Atypical Femur Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Bone Contusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Contusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Fall **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Joint Injury **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Procedural Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Skin Abrasion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Skin Laceration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Tooth Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Traumatic Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 **Term:** Alanine Aminotransferase Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Amylase Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Aspergillus Test Positive **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Blood Beta-D-Glucan Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Blood Creatinine Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Blood Fibrinogen Decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Blood Lactate Dehydrogenase Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Gamma-Glutamyltransferase Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Haemoglobin Decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Lipase Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Lymphocyte Count Decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Neutrophil Count Decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Platelet Count Decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Weight Decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Weight Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 24.1 **Term:** Decreased Appetite **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hyperkalaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypertriglyceridaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hyperuricaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypoalbuminaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypocalcaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypoglycaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypokalaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Lipid Metabolism Disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Zinc Deficiency **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Back Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Immobilisation Syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Metatarsalgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Muscle Spasms **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Myalgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Osteonecrosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Osteonecrosis of Jaw **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Osteoporosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Rheumatoid Arthritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Spinal Osteoarthritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Acute Lymphocytic Leukaemia Recurrent **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pyogenic Granuloma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 24.1 **Term:** Dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypoaesthesia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Intercostal Neuralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Restless Legs Syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Toxic Encephalopathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Anxiety **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Depression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Insomnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Chronic Kidney Disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Haematuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Urinary Retention **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Benign Prostatic Hyperplasia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Asthma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Epistaxis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Oropharyngeal Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pleural Effusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Acne **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Dermal Cyst **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Dermatitis Acneiform **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Drug Eruption **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Dry Skin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Eczema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Haemorrhage Subcutaneous **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Ingrowing Nail **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Pruritus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Purpura **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Skin Atrophy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Skin Exfoliation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Skin Induration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Skin Ulcer **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Toxic Skin Eruption **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Haematoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 24.1 **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 24.1 #### Serious Events **Term:** Immune Thrombocytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Atrial Flutter **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Cataract **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Gastrointestinal Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Multiple Organ Dysfunction Syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Liver Disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Anaphylactic Reaction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Appendiceal Abscess **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Bronchiolitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Cellulitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 19 **Term:** Covid-19 **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 7 **Num At Risk:** 19 **Term:** Pneumonia Bacterial **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Pneumonia Fungal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Pyelonephritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Septic Shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Atypical Femur Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Diabetes Mellitus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Hyperkalaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Osteonecrosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Subarachnoid Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 19 **Term:** Renal Impairment **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 19 **Time Frame:** Up to 3 year 6 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 19 **Units:** Participants ### Group **ID:** BG000 **Title:** Ibrutinib 420 mg **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 16.24 **Value:** 40.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** Less Than or Equal to 17 years (adolescent) #### Measurement **Group ID:** BG000 **Value:** 18 **Category Title:** From 18 to 64 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 7 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 12 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 19 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 19 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 19 **Class Title:** JAPAN **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Customized **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 6 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Region of Enrollment **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Other Details:** If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Janssen Pharmaceutical K.K. **Phone:** 844-434-4210 **Title:** EXECUTIVE MEDICAL DIRECTOR ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ### Outcome Measure 17 ### Outcome Measure 18 ### Outcome Measure 19 ### Outcome Measure 20 ### Outcome Measure 21 ### Outcome Measure 22 ### Outcome Measure 23 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84.2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 68.8 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** Here, 'NA' indicates that median and upper limit of 95% confidence interval were not estimable due to the less number of events. - **Group ID:** OG000 - **Lower Limit:** 5.30 - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 9.1 - **Spread:** - **Upper Limit:** 51.2 - **Value:** 26.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 20.3 - **Spread:** - **Upper Limit:** 66.5 - **Value:** 42.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 28.9 - **Spread:** - **Upper Limit:** 75.6 - **Value:** 52.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 24.4 - **Spread:** - **Upper Limit:** 71.1 - **Value:** 47.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 24.4 - **Spread:** - **Upper Limit:** 71.1 - **Value:** 47.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 20.3 - **Spread:** - **Upper Limit:** 66.5 - **Value:** 42.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 16.3 - **Spread:** - **Upper Limit:** 61.6 - **Value:** 36.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12.6 - **Spread:** - **Upper Limit:** 56.6 - **Value:** 31.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12.6 - **Spread:** - **Upper Limit:** 56.6 - **Value:** 31.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12.6 - **Spread:** - **Upper Limit:** 56.6 - **Value:** 31.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 16.3 - **Spread:** - **Upper Limit:** 61.6 - **Value:** 36.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12.6 - **Spread:** - **Upper Limit:** 56.6 - **Value:** 31.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 9.1 - **Spread:** - **Upper Limit:** 51.2 - **Value:** 26.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.3 - **Spread:** - **Upper Limit:** 33.1 - **Value:** 10.5 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.08 - **Spread:** - **Upper Limit:** 1.77 - **Value:** 0.270 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.08 - **Spread:** - **Upper Limit:** 0.87 - **Value:** 0.250 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.06 - **Spread:** - **Upper Limit:** 0.64 - **Value:** 0.150 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.01 - **Spread:** - **Upper Limit:** 0.59 - **Value:** 0.140 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 9 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.05 - **Spread:** - **Upper Limit:** 0.56 - **Value:** 0.140 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 **Units:** Participants #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 28.9 - **Spread:** - **Upper Limit:** 75.6 - **Value:** 52.6 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3146.9 - **Upper Limit:** - **Value:** 3683.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4287.2 - **Upper Limit:** - **Value:** 4024.8 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1797.4 - **Upper Limit:** - **Value:** 2929.3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 7 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4277.2 - **Upper Limit:** - **Value:** 4035.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 **Units:** Participants #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 366.07 - **Upper Limit:** - **Value:** 490.45 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 508.08 - **Upper Limit:** - **Value:** 478.01 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.78 - **Spread:** - **Upper Limit:** 5.75 - **Value:** 3.87 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.75 - **Spread:** - **Upper Limit:** 5.43 - **Value:** 4.02 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.4 - **Spread:** - **Upper Limit:** 5.2 - **Value:** 4.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.8 - **Spread:** - **Upper Limit:** 10.2 - **Value:** 4.4 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 106164 - **Upper Limit:** - **Value:** 194211 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 31966 - **Upper Limit:** - **Value:** 162457 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 748511 - **Upper Limit:** - **Value:** 1350160 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 **Units:** Participants **Class:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 **Units:** Participants #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1656.2 - **Upper Limit:** - **Value:** 2643.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 506.57 - **Upper Limit:** - **Value:** 2659.2 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 968.83 - **Upper Limit:** - **Value:** 1976.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 999.00 - **Upper Limit:** - **Value:** 2547.6 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 585.84 - **Upper Limit:** - **Value:** 1803.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 6 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 999.00 - **Upper Limit:** - **Value:** 2547.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 **Units:** Participants #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 91.874 - **Upper Limit:** - **Value:** 185.37 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 82.292 - **Upper Limit:** - **Value:** 203.16 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.88 - **Spread:** - **Upper Limit:** 6.18 - **Value:** 4.00 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.00 - **Spread:** - **Upper Limit:** 5.28 - **Value:** 4.02 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5.2 - **Spread:** - **Upper Limit:** 6.5 - **Value:** 5.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5.4 - **Spread:** - **Upper Limit:** 5.4 - **Value:** 5.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 68392 - **Upper Limit:** - **Value:** 251681 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** Here, 'NA' indicates that standard deviation could not be calculated for a single participant. - **Group ID:** OG000 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** 111922 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 653626 - **Upper Limit:** - **Value:** 2148283 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 **Units:** Participants **Class:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 **Units:** Participants #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 478.74 - **Upper Limit:** - **Value:** 1766.1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** Here, 'NA' indicates that standard deviation could not be calculated for a single participant. - **Group ID:** OG000 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** 3752.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death based on the National Institutes of Health (NIH) Consensus Development Project Criteria (2014). CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and chronic graft versus host disease (cGVHD) progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. **Parameter Type:** NUMBER **Population Description:** All treated analysis set included all enrolled participants who received at least 1 dose of study drug. **Reporting Status:** POSTED **Time Frame:** Up to 3 year 6 months **Title:** Overall Response Rate (ORR) **Type:** PRIMARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 2 **Description:** Sustained response rate was defined as percentage of participants with NIH defined CR or PR that was sustained for at least 20 weeks. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site. **Parameter Type:** NUMBER **Population Description:** All treated analysis set included all enrolled participants who received at least 1 dose of study drug and achieved PR or better response. **Reporting Status:** POSTED **Time Frame:** Up to 3 year 6 months **Title:** Sustained Response Rate **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 3 **Description:** DOR is defined as the duration from the date of initial response (CR or PR) to the date of progressive cGVHD or death, whichever occurred first. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** All treated analysis set included all enrolled participants who received at least 1 dose of study drug and achieved PR or better response. **Reporting Status:** POSTED **Time Frame:** Up to 3 year 6 months **Title:** Duration of Response (DOR) **Type:** SECONDARY **Unit of Measure:** Months ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 4 **Description:** cGVHD response rate was defined as percentage of participants with NIH defined CR or PR at each timepoint. CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** All treated analysis set included all enrolled participants who received at least 1 dose of study drug. **Reporting Status:** POSTED **Time Frame:** Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157 **Title:** cGVHD Response Rate at Each Timepoints **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 5 **Description:** Change in the amount of corticosteroid required over time was reported. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** All treated analysis set included all enrolled participants who received at least 1 dose of study drug. Here, 'n' (number analyzed) represents number of participants evaluable at the specified timepoints. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 24, 48, 96, and 144 **Title:** Change in the Amount of Corticosteroid Required Over Time **Type:** SECONDARY **Unit of Measure:** Milligrams per kilograms per day ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 6 **Description:** Percentage of participants with overall improvement in Lee cGVHD symptom scale score was reported. Lee cGVHD symptom scale is a patient-reported symptom scale used to measure symptom burden and has 7 subscales (Skin, Eyes and Mouth, Breathing, Eating and Digestion, Muscles and Joints, Energy, and Mental and Emotional) with ratings as follows: 0-Not at all, 1-Slightly, 2-Moderately, 3-Quite a bit, 4-Extremely, with lower values representing a better outcome. A score was calculated for each subscale by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 with a higher score indicating worse symptoms. An overall score was calculated as the average of these 7 subscales if at least 4 subscales had valid scores. A change of greater than or equal to (\>=) 7 points on the Lee cGVHD symptom scale overall score was considered significant and relates to improvement in quality of life (QoL). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** All treated analysis set included all enrolled participants who received at least 1 dose of study drug. **Reporting Status:** POSTED **Time Frame:** Up to 3 year 6 months **Title:** Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 7 **Description:** An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs are adverse events with onset during the treatment phase or that were a consequence of a preexisting condition that has worsened since baseline, and occurred during treatment or within 30 days following the last dose of study treatment, or any adverse event that was considered study treatment-related regardless of the start date of the event. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The safety analysis set included all enrolled participants who received at least 1 dose of study drug. **Reporting Status:** POSTED **Time Frame:** Up to 3 year 6 months **Title:** Number of Participants With Treatment-emergent Adverse Events (TEAEs) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 8 **Description:** AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of ibrutinib. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The pharmacokinetic (PK) evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib **Type:** SECONDARY **Unit of Measure:** hours*nanograms per milliliter (h*ng/mL) ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 9 **Description:** AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of ibrutinib. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints. **Reporting Status:** POSTED **Time Frame:** 0 to 24 hours (Day 1 of Weeks 1 and 2) **Title:** Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib **Type:** SECONDARY **Unit of Measure:** hour*ng/mL ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 10 **Description:** Cmax is defined as maximum observed plasma concentration of ibrutinib. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Maximum Observed Plasma Concentration (Cmax) of Ibrutinib **Type:** SECONDARY **Unit of Measure:** Nanograms per milliliter (ng/mL) ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 11 **Description:** Tmax is defined as time to reach the maximum observed plasma concentration of ibrutinib. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib **Type:** SECONDARY **Unit of Measure:** Hours ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 12 **Description:** T1/2 is defined as elimination half-life of ibrutinib. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Elimination Half-Life (t1/2) of Ibrutinib **Type:** SECONDARY **Unit of Measure:** Hours ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 13 **Description:** CL/F is defined as apparent clearance of ibrutinib. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Apparent Clearance (CL/F) of Ibrutinib **Type:** SECONDARY **Unit of Measure:** Milliliters per hour (mL/h) ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 14 **Description:** Vd/F is defined as apparent volume of distribution of ibrutinib. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Apparent Volume of Distribution (Vd/F) of Ibrutinib **Type:** SECONDARY **Unit of Measure:** Milliliters (mL) ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 15 **Description:** AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of ibrutinib. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib **Type:** SECONDARY **Unit of Measure:** hour*ng/mL ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 16 **Description:** AUC(0-last) is defined as area under the plasma concentration-time curve from time zero to time of last measurable concentration of PCI-45227. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227 **Type:** SECONDARY **Unit of Measure:** h*ng/mL ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 17 **Description:** AUC(0-24) is defined as area under the plasma concentration-time curve from time zero to 24 hours of PCI-45227. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints. **Reporting Status:** POSTED **Time Frame:** 0 to 24 hours (Day 1 of Weeks 1 and 2) **Title:** Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227 **Type:** SECONDARY **Unit of Measure:** hour*ng/mL ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 18 **Description:** Cmax is defined as maximum observed plasma concentration of PCI-45227. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Maximum Observed Plasma Concentration (Cmax) of PCI-45227 **Type:** SECONDARY **Unit of Measure:** ng/mL ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 19 **Description:** Tmax is defined as time to reach the maximum observed plasma concentration of PCI-45227. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227 **Type:** SECONDARY **Unit of Measure:** Hours ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 20 **Description:** T1/2 is defined as elimination half-life of PCI-45227. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** The PK evaluable analysis set is defined as all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Elimination Half-Life (t1/2) of PCI-45227 **Type:** SECONDARY **Unit of Measure:** Hours ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 21 **Description:** CL/F is defined as apparent clearance of PCI-45227. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Apparent Clearance (CL/F) of PCI-45227 **Type:** SECONDARY **Unit of Measure:** mL/h ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 22 **Description:** Vd/F is defined as apparent volume of distribution of PCI-45227. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Apparent Volume of Distribution (Vd/F) of PCI-45227 **Type:** SECONDARY **Unit of Measure:** mL ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg #### Outcome Measure 23 **Description:** AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time of PCI-45227. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The PK evaluable analysis set included all enrolled participants who received at least one dose of study drug and had at least 1 postdose PK sample obtained. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints. **Reporting Status:** POSTED **Time Frame:** Day 1 of Weeks 1 and 2 **Title:** Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227 **Type:** SECONDARY **Unit of Measure:** hour*ng/mL ##### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** OG000 **Title:** Ibrutinib 420 mg ### Participant Flow Module #### Group **Description:** Participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) received ibrutinib 420 milligrams (mg) (3\*140 mg capsule) orally once daily on Week 1 Day 1 until participants had intervening unacceptable toxicity or met other criteria for discontinuation. **ID:** FG000 **Title:** Ibrutinib 420 mg #### Period **Title:** Overall Study ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 19 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 11 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT03681379 **Acronym:** PALMAréa **Brief Title:** Pharmacokinetics of Levosimendan in Pediatric Intensive Care Units **Official Title:** Pharmacokinetics of Levosimendan, OR1855 and OR1896 in Neonates and Children With or Without Extracorporeal Membrane Oxygenation #### Organization Study ID Info **ID:** RC16_0114 #### Organization **Class:** OTHER **Full Name:** Nantes University Hospital ### Status Module #### Completion Date **Date:** 2020-10-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2018-09-24 **Type:** ACTUAL **Last Update Submit Date:** 2018-09-21 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2020-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2018-10-01 **Type:** ESTIMATED **Status Verified Date:** 2018-09 #### Study First Post Date **Date:** 2018-09-24 **Type:** ACTUAL **Study First Submit Date:** 2018-09-18 **Study First Submit QC Date:** 2018-09-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nantes University Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** To describe pharmacokinetics of levosimendan in neonates and children supported or not with extracorporeal circulation devices (ECMO, CRRT) **Detailed Description:** Levosimendan is a calcium sensitiver wih inotropic effects. It's use in the context of acute or chronic heart failure in children has yet to be defined. Due to physical proprieties of levosimendan and metabolites, we hypothesized that concomitant use of extracorporeal devices such as ECMO will cause major pharmacokinetic variations. Furthermore, pharmacokinetics of levosimendan in children with multiple organ failure has to be specify. ### Conditions Module **Conditions:** - Acute Heart Failure **Keywords:** - Levosimendan - pharmacokinetics - children - acute heart failure ### Design Module #### Bio Spec **Description:** Patients with acute circulatory insufficiency are equipped with a central venous line or catheterization for hemodynamic monitoring and biological assessment in context of routine care. There will be no specific interventions to the study participants like additional venipuncture for this study. The volume required for the analyzes (0.5 ml, 13 times over a period of 8 days) are issue from hemodynamic monitoring and biological assessment in context of routine care . This volume is compatible with the current french regulation on non interventional research. **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Area under the plasma concentration versus time curve (AUC) of levosimendan, OR 1855 and OR 1896. Samples will be collected over a period in of 192h in context of routine care **Measure:** First parameter of the pharmacokinetics of levosimendan, OR1855, OR1896 (Area under the plasma concentration versus time curve (AUC) ) **Time Frame:** At the end of the study, after 2 years. **Description:** distribution volume of levosimendan, OR 1855 and OR 1896. Samples will be collected over a period in of 192h in context of routine care **Measure:** second parameter of the pharmacokinetics of levosimendan, OR1855, OR1896 (distribution volume) **Time Frame:** At the end of the study, after 2 years. **Description:** half-life time of levosimendan, OR 1855 and OR 1896. Samples will be collected over a period in of 192h in context of routine care **Measure:** third parameter of the pharmacokinetics of levosimendan, OR1855, OR1896 (half-life time) **Time Frame:** At the end of the study, after 2 years. **Description:** Peak Plasma Concentration (Cmax) of levosimendan, OR 1855 and OR 1896. Samples will be collected over a period in of 192h in context of routine care **Measure:** fourth parameter of the pharmacokinetics of levosimendan, OR1855, OR1896 (Peak Plasma Concentration (Cmax)) **Time Frame:** At the end of the study, after 2 years. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All children admitted in pediatric intensive care units with planned infusion of 0.2 mcg/kg/min of levosimendan over 24h in context of routine care * Arterial line or central venous catheter inserted for blood sampling procedures in context of routine care. Exclusion Criteria: * Absence of clear parental status or information **Maximum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT **Study Population:** children admitted in pediatric intensive care units for acute heart failure ### Contacts Locations Module #### Locations **Location 1:** **City:** Nantes **Country:** France **Facility:** CHU de Nantes ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Kivikko M, Antila S, Eha J, Lehtonen L, Pentikainen PJ. Pharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure. Int J Clin Pharmacol Ther. 2002 Oct;40(10):465-71. doi: 10.5414/cpp40465. **PMID:** 12395979 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Intervention Browse Module - Browse Branches - Abbrev: CaAg - Name: Cardiotonic Agents - Abbrev: VaDiAg - Name: Vasodilator Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1805 - Name: Simendan - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01555879 **Brief Title:** Real-world Clinical Efficacy of Abatacept in the T3 Data Registry **Official Title:** Abatacept in T3: A Characterization of Abatacept's Efficacy and Outcomes From a Real-Word Clinical Practice Information Hub on Novel Patient Sub-Groups #### Organization Study ID Info **ID:** IM101-322 #### Organization **Class:** INDUSTRY **Full Name:** Arthritis Northwest PLLC #### Secondary ID Infos **Domain:** Arthritis Northwest **ID:** ANW_20110816 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2016-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-11-06 **Type:** ACTUAL **Last Update Submit Date:** 2017-11-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-11 **Type:** ACTUAL #### Start Date **Date:** 2012-03 **Status Verified Date:** 2017-11 #### Study First Post Date **Date:** 2012-03-16 **Type:** ESTIMATED **Study First Submit Date:** 2012-02-29 **Study First Submit QC Date:** 2012-03-14 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Bristol-Myers Squibb #### Lead Sponsor **Class:** INDUSTRY **Name:** Arthritis Northwest PLLC #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to assess the effectiveness of Abatacept in real-world clinical practice. The main hypothesis to be examined in this study is, "Abatacept's effectiveness results in a single real-world clinic (n = 100) are reproducible at another site (n \~= 200)". **Detailed Description:** Two secondary hypotheses that will be tested are: * Abatacept aids in achieving low disease activity or clinical remission in patients of the following Rheumatoid Arthritis (RA) sub-groups: RF+/CCP+, RF+/CCP- RF-/CCP+ RF-/CCP-; first time on a bio-tech drug; having previously failed a biological drug; having interstitial lung disease; identified as disabled; twenty-eight individual joints identified as {swollen, painful, tender, deformed or having decreased range of motion}; on or not on oral DMARD; age; or gender. * A database with sufficient attributes exists from which a patient's efficacy on abatacept is accurately predictable. ### Conditions Module **Conditions:** - Arthritis, Rheumatoid **Keywords:** - Retrospective - Database - Data warehouse - Data mining - Collaborative effectiveness - Comparative effectiveness - Outcome based medicine - Evidence based medicine ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 200 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All patients in T3 who have used Abatacept for at least 3 months between 2009-03-17 and 2011-11-30. **Intervention Names:** - Drug: Abatacept **Label:** All patients ### Interventions #### Intervention 1 **Arm Group Labels:** - All patients **Description:** As prescribed by a doctor for patient medical care. **Name:** Abatacept **Other Names:** - Orencia Intravenous **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Determine the efficacy of abatacept by analyzing the change in CDAI, DAS28, and RAPID3 scores. **Time Frame:** Change from baseline in CDAI, DAS28, and RAPID3 scores at approximately 6 months. #### Secondary Outcomes **Measure:** Determine the efficacy of abatacept by analyzing the change in CDAI, DAS28, and RAPID3 scores. **Time Frame:** Change from baseline in CDAI, DAS28, and RAPID3 scores at approximately 3 months. **Measure:** Determine the efficacy of abatacept by analyzing the change in CDAI, DAS28, and RAPID3 scores. **Time Frame:** Change from baseline in CDAI, DAS28, and RAPID3 scores at approximately 9 months. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosed with rheumatoid arthritis * Have used Abatacept for 3 or more months Exclusion Criteria: * None **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** All rheumatoid arthritis patients from a single site who have been on Abatacept for greater than 3 months. ### Contacts Locations Module #### Locations **Location 1:** **City:** Spokane **Country:** United States **Facility:** Arthritis Northwest **State:** Washington **Zip:** 99208 #### Overall Officials **Official 1:** **Affiliation:** Arthritis Northwest PLLC **Name:** Keith Knapp, Ph.D. **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Arthritis Northwest PLLC **Name:** Gary Craig, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Michael Schiff, Coralie Poncet, and Manuela Le Bars International Journal of Clinical Rheumatology 2010 5:5, 581-591 **Citation:** Pincus T, Swearingen CJ, Bergman M, Yazici Y. RAPID3 (Routine Assessment of Patient Index Data 3), a rheumatoid arthritis index without formal joint counts for routine care: proposed severity categories compared to disease activity score and clinical disease activity index categories. J Rheumatol. 2008 Nov;35(11):2136-47. doi: 10.3899/jrheum.080182. Epub 2008 Sep 15. **PMID:** 18793006 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases - ID: D000003240 - Term: Connective Tissue Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M4480 - Name: Arthritis, Rheumatoid - Relevance: HIGH - As Found: Arthritis, Rheumatoid - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001172 - Term: Arthritis, Rheumatoid ### Intervention Browse Module - Ancestors - ID: D000082082 - Term: Immune Checkpoint Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018501 - Term: Antirheumatic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M483 - Name: Abatacept - Relevance: HIGH - As Found: Panel - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: LOW - As Found: Unknown - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069594 - Term: Abatacept ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03209479 **Brief Title:** Copaxone Subcutaneous Injection Syringe Special Drug Use-Result Investigation (All-Case Investigation) "Prevention of Relapse of Multiple Sclerosis" **Official Title:** Copaxone Subcutaneous Injection Syringe Special Drug Use-Result Investigation (All-Case Investigation) "Prevention of Relapse of Multiple Sclerosis" #### Organization Study ID Info **ID:** Glatiramer-5001 #### Organization **Class:** INDUSTRY **Full Name:** Takeda #### Secondary ID Infos **Domain:** jRCT **ID:** jRCT1080223004 **Type:** REGISTRY ### Status Module #### Completion Date **Date:** 2024-03-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2024-03-31 **Type:** ACTUAL #### Start Date **Date:** 2015-11-24 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2017-07-06 **Type:** ACTUAL **Study First Submit Date:** 2017-07-04 **Study First Submit QC Date:** 2017-07-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Takeda #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate the safety and efficacy of Copaxone subcutaneous injection syringe (hereinafter referred to as Copaxone) in patients with multiple sclerosis in the routine clinical setting. **Detailed Description:** The drug being tested in this study is called Glatiramer acetate is being tested to treat people who have Multiple sclerosis. This study will look at the safety and efficacy of Glatiramer acetate in patients with multiple sclerosis in the routine clinical setting. The study will enroll approximately 1000 patients. • Glatiramer acetate subcutaneous injection syringe This multi-center trial will be conducted in Japan. ### Conditions Module **Conditions:** - Multiple Sclerosis ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1332 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** For adults, a 20 mg dose of glatiramer acetate will be subcutaneously administered once daily. Participants will receive interventions as part of routine medical care. **Intervention Names:** - Drug: Glatiramer acetate **Label:** Glatiramer acetate ### Interventions #### Intervention 1 **Arm Group Labels:** - Glatiramer acetate **Description:** Copaxone subcutaneous injection syringe **Name:** Glatiramer acetate **Other Names:** - Copaxone subcutaneous injection syringe **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Percentage of participants who had one or more adverse events **Time Frame:** Up to 24 months **Description:** The annual relapse rate (ARR) after the start of treatment will be calculated throughout study. **Measure:** Annual Relapse Rate (ARR) **Time Frame:** Up to 24 months #### Secondary Outcomes **Measure:** Changes in the number of lesions from brain MRI findings **Time Frame:** Up to 24 months **Description:** EDSS is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. EDSS scale ranges from 0 to 10 in 0.5 unit increments and higher score refers to people with higher levels of disability by multiple sclerosis. **Measure:** Changes in functional evaluation scores (Expanded Disability Status Scale [EDSS]) **Time Frame:** Up to 24 months **Description:** FS is based on a standard neurological examination; the 7 functional systems plus "other" (Pyramidal, Cerebellar, Brainstem, Sensory, Bowel and bladder function, Visual function, Cerebral \[or mental\] functions, other) are rated. Each FS is scored on a scale of 0 (no disability) to 5 or 6 (more severe disability), and total score ranging from 0 to 40. Higher score in each functional system refers to people with higher levels of disability by multiple sclerosis. **Measure:** Changes in functional evaluation scores (Functional Systems [FS]) **Time Frame:** Up to 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - All patients treated with Copaxone from the first day of market launch of the product Exclusion Criteria: -None **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** The study population will consist of all participants with a diagnosis of multiple sclerosis and received their first dose of Copaxone/glatiramer acetate. ### Contacts Locations Module #### Locations **Location 1:** **City:** Tokyo **Country:** Japan **Facility:** Takeda selected site #### Overall Officials **Official 1:** **Affiliation:** Takeda **Name:** Study Director **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Access Criteria:** IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement. **Description:** Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement. **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR **IPD Sharing:** YES ### References Module #### See Also Links **Label:** To obtain more information on the study, click here/on this link **URL:** https://clinicaltrials.takeda.com/study-detail/5f6b60234db2bf003ab49722 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009103 - Term: Multiple Sclerosis - ID: D000012598 - Term: Sclerosis ### Intervention Browse Module - Ancestors - ID: D000000276 - Term: Adjuvants, Immunologic - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000018501 - Term: Antirheumatic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M297 - Name: Glatiramer Acetate - Relevance: HIGH - As Found: Replace - ID: M147897 - Name: (T,G)-A-L - Relevance: HIGH - As Found: Replace - ID: M3628 - Name: Adjuvants, Immunologic - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068717 - Term: Glatiramer Acetate - ID: C000021759 - Term: (T,G)-A-L ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04279379 **Brief Title:** Sintilimab and Decitabine for Patients With Relapsed/Refractory or Advanced NK/T-cell Lymphoma **Official Title:** Combination of Sintilimab and Decitabine for Patients With Relapsed/Refractory or Advanced NK/T-cell Lymphoma : a Single Arm,Open-lable,Phase II Study #### Organization Study ID Info **ID:** TRhos-ENKTCL-2 #### Organization **Class:** OTHER **Full Name:** Beijing Tongren Hospital ### Status Module #### Completion Date **Date:** 2022-12-31 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-05-07 **Type:** ACTUAL **Last Update Submit Date:** 2020-05-06 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2020-04-01 **Type:** ACTUAL **Status Verified Date:** 2020-05 #### Study First Post Date **Date:** 2020-02-21 **Type:** ACTUAL **Study First Submit Date:** 2020-02-19 **Study First Submit QC Date:** 2020-02-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Beijing Tongren Hospital #### Responsible Party **Investigator Affiliation:** Beijing Tongren Hospital **Investigator Full Name:** JING-WEN WANG **Investigator Title:** Director of department of hematology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate the efficacy and safety of Sintilimab in combination with decitabine in the treatment of Relapsed/Refractory or advanced NK/T-cell lymphoma patients **Detailed Description:** Previous study has confirmed the efficacy of anti-PD-1 antibodies (including pembrolizumab or sintilimab). However, the CR rate of PD-1 antibody monotherapy is too low. Previous studies have demonstrated that decitabine may activate the T cells and enhance the efficacy of PD-1 antibodies in Hodgkin Lymphoma. Thus, the investigators aim to evaluate the efficacy and safety of sintilimab in combination with decitabine in the treatment of NK/T cell lymphoma. ### Conditions Module **Conditions:** - Extranodal NK/T-cell Lymphoma **Keywords:** - extranodal NK/T-cell lymphoma - PD-1 blockade - decitabine - sintilimab - hypomethylation - epigenetics ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** treatment with sintilimab and decitabine. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Sintilimab,200mg,ivdrip,day1 Decitabine 10mg d1-5, ivdrip, repeated every 3 weeks. **Intervention Names:** - Drug: Sintilimab - Drug: Decitabine **Label:** treatment arm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - treatment arm **Description:** 200mg d1,ivdrip, repeated every 3 weeks **Name:** Sintilimab **Other Names:** - anti-PD-1-antibody **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - treatment arm **Description:** 10mg d1-5, ivdrip,repeated every 3 weeks **Name:** Decitabine **Other Names:** - hypomethylating agents **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** evaluated by PET-CT and MRI, according to Lugano 2014 criteria **Measure:** complete response rate **Time Frame:** 24 weeks ±7 days #### Secondary Outcomes **Description:** evaluated by PET-CT and MRI, according to Lugano 2014 criteria **Measure:** overall response rate **Time Frame:** 24 weeks ±7 days **Description:** time from date of enrollment to date of disease progression, death of any reason, whichever comes first **Measure:** 1-year progression free survival rate **Time Frame:** up to 1year after enrollment **Description:** time from date of enrollment to date death of any reason **Measure:** 1-year overall survival rate **Time Frame:** up to 1year after enrollment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Histopathology and immunohistochemistry confirmed diagnosis of NK/Tcell lymphoma according to WHO 2016 criteria. * refractory or relapsed after initial remission, or stage III-IV de novo patients * PET/CT or CT/MRI with at least one objectively evaluable lesion. * General status ECOG score 0-3 points. * The laboratory test within 1 week before enrollment meets the following conditions: Blood routine: Hb\>80g/L, PLT\>50×10e9/L. Liver function: ALT, AST, TBIL ≤2 times the upper limit of normal. Renal function: Cr is normal. Cardiac function: LVEF≥50%, ECG does not suggest any acute myocardial infarction, arrhythmia or atrioventricular conduction above I Blocking. * Sign the informed consent form Exclusion Criteria: Active infection requires ICU treatment. Concomitant HIV infection or active infection with HBV, HCV. Patients who are infected with HBV but not active hepatitis at the same time are notexcluded. Significant organ dysfunction Pregnant and lactating women. Had a history of autoimmune diseases, and disease was active in the last 6 months. Those who were known to be allergic to drugs in the study regimen. Patients with other tumors who require surgery or chemotherapy within 6 months. • Other experimental drugs are being used. **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** LIANG WANG, M.D. **Phone:** +8615013009093 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Liang Wang, MD - **Phone:** +8615001108693 - **Role:** CONTACT **Country:** China **Facility:** Beijing Tongren Hospital **Status:** RECRUITING **Zip:** 100730 #### Overall Officials **Official 1:** **Affiliation:** Beijing Tongren Hospital **Name:** Jing-wen Wang, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000008228 - Term: Lymphoma, Non-Hodgkin ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11220 - Name: Lymphoma - Relevance: HIGH - As Found: Lymphoma - ID: M18829 - Name: Lymphoma, T-Cell - Relevance: HIGH - As Found: T-cell Lymphoma - ID: M18833 - Name: Lymphoma, T-Cell, Peripheral - Relevance: HIGH - As Found: T-cell Lymphoma - ID: M27676 - Name: Lymphoma, Extranodal NK-T-Cell - Relevance: HIGH - As Found: Extranodal NK/T-cell Lymphoma - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M11222 - Name: Lymphoma, Non-Hodgkin - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: HIGH - As Found: Lymphoma - ID: T4496 - Name: Peripheral T-cell Lymphoma - Relevance: HIGH - As Found: T-cell Lymphoma - ID: T2165 - Name: Extranodal Nasal NK/T Cell Lymphoma - Relevance: HIGH - As Found: NK/T-cell Lymphoma ### Condition Browse Module - Meshes - ID: D000008223 - Term: Lymphoma - ID: D000016399 - Term: Lymphoma, T-Cell - ID: D000016411 - Term: Lymphoma, T-Cell, Peripheral - ID: D000054391 - Term: Lymphoma, Extranodal NK-T-Cell ### Intervention Browse Module - Ancestors - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1697 - Name: Decitabine - Relevance: HIGH - As Found: Above - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077209 - Term: Decitabine ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT06358079 **Brief Title:** Re-infusion of Unwashed Shed Blood During Off-pump Surgery **Official Title:** Isolated Cardiotomy Circuit for Re-infusion of Unwashed Shed Blood During Off-pump Coronary Artery Surgery #### Organization Study ID Info **ID:** 258 #### Organization **Class:** OTHER **Full Name:** Damascus University ### Status Module #### Completion Date **Date:** 2026-03-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-10 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-06 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-03-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-03-27 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-04-10 **Type:** ACTUAL **Study First Submit Date:** 2024-03-27 **Study First Submit QC Date:** 2024-04-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Damascus University #### Responsible Party **Investigator Affiliation:** Damascus University **Investigator Full Name:** Mohammad Bashar Izzat **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** To assess the efficacy and side-effects of re-infusion of unwashed shed blood during off-pump coronary artery surgery using a novel cardiotomy circuit. **Detailed Description:** Introduction Blood transfusion is often required during cardiac surgical operations, and may be associated with known risks and complications. Off-pump coronary artery surgery has been shown to be associated with reduced need for blood transfusion, and cell-savers are widely used as an additional method for reducing blood transfusion demands. Auto-transfusion of unwashed suctioned blood intra-operatively is thought to increase the inflammatory response and infective complications, but data related to this approach are scares. Aims To assess the effects and benefits of using an isolated cardiotomy circuit for re-infusion of unwashed shed blood during off-pump surgery and compare it to the conventional no re-infusion technique. Assessments will focus on: * clinical outcome * transfusion requirements * inflammatory response * alveolar/arterial oxygen pressure gradients * cognitive status * cost-benefit Study design A prospective study involving patients undergoing off-pump coronary artery bypass surgery. Patients will be randomized to two groups; an isolated cardiotomy circuit for re-infusion of unwashed shed blood will be used in group (a) and the conventional no re-infusion technique will be used in group (b). Participants Patients undergoing off-pump coronary artery bypass surgery. Setting Damascus University Cardiac Surgery Hospital ### Conditions Module **Conditions:** - Coronary Artery Disease - Blood Transfusion Complication - Cardiovascular Complication **Keywords:** - surgery - coronary artery bypass grafting - blood - off-pump - auto-transfusion ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** A prospective study involving patients undergoing off-pump coronary artery bypass surgery. Patients will be randomized to two groups; an isolated cardiotomy circuit for re-infusion of unwashed shed blood will be used in group (a) and the conventional no re-infusion technique will be used in group (b). ##### Masking Info **Masking:** SINGLE **Masking Description:** Outcome assessor will be blinded to the group type when analyzing data **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Re-infusion of unwashed shed blood **Intervention Names:** - Procedure: Re-infusion of unwashed shed blood **Label:** Group 1: Use of circuit **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No re-infusion of unwashed shed blood **Label:** Group 2: No circuit **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Group 1: Use of circuit **Description:** Use of an isolated cardiotomy circuit for re-infusion of unwashed shed blood during off-pump coronary artery surgery **Name:** Re-infusion of unwashed shed blood **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** volume of blood (ml) transfused **Measure:** blood transfusion requirements **Time Frame:** up to 5 days post-operatively **Description:** changes in IL-6 **Measure:** inflammatory response **Time Frame:** pre-operatively, immediately post-operatively, and 24 hours post-operatively **Description:** changes in alveolar/arterial oxygen pressure gradients peri-operatively **Measure:** alveolar/arterial oxygen pressure gradients **Time Frame:** pre-, 4 hours post-operatively, and post-extubation **Description:** cost of blood products, circuits and hospital stay **Measure:** cost-benefit **Time Frame:** up to 5 days postoperatively **Description:** Changes in S-100 **Measure:** Neuro-markers **Time Frame:** pre-operatively, immediately post-operatively, and 24 hours post-operatively **Description:** changes in CK-MB **Measure:** myocardial marker CK-MB **Time Frame:** pre-operatively, immediately post-operatively, and 24 hours post-operatively **Description:** changes in troponin-I **Measure:** myocardial marker troponin-I **Time Frame:** pre-operatively, immediately post-operatively, and 24 hours post-operatively **Description:** volume (ml) of blood lost **Measure:** blood loss **Time Frame:** up to 24 hours post-operatively **Description:** changes in C3a **Measure:** complement response **Time Frame:** pre-operatively, immediately post-operatively, and 24 hours post-operatively ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All patients undergoing isolated off-pump coronary artery bypass surgery between March 1st, 2024 and March 31st, 2026. Exclusion Criteria: * Missing data. * Patients outside the study period. * Patients under the age of 40 years or over the age of 75 years. * Patients with impaired left ventricular function (EF less the 40%). * Patients with history of renal failure, hepatic failure, CVA, or TIA. * Patients who have not stopped anticoagulants (except aspirin) for 4 days preoperatively. * Emergency operations. **Maximum Age:** 75 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Albaraa Bara, MD **Phone:** 0934206291 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Nour Kara Tahhan, MD **Phone:** 0933295582 **Role:** CONTACT #### Locations **Location 1:** **City:** Damascus **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mohammad Bashar Izzat, FRCS - **Phone:** +963943240820 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Albaraa Bara, MD - **Phone:** 0934206291 - **Role:** CONTACT **Country:** Syrian Arab Republic **Facility:** Damascus University Cardiac Surgery Hospital **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Damascus University **Name:** Mohammad Bashar Izzat, FRCS(CTh) **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **Access Criteria:** Open to all **Description:** Data will be deposited in a Data Repository **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR - ANALYTIC_CODE **IPD Sharing:** YES **Time Frame:** Upon completion of the study and will be there permanently ### References Module #### References **Citation:** Liumbruno GM, Waters JH. Unwashed shed blood: should we transfuse it? Blood Transfus. 2011 Jul;9(3):241-5. doi: 10.2450/2011.0109-10. Epub 2011 Apr 20. No abstract available. **PMID:** 21627923 **Citation:** Konig G, Waters JH. Washing and filtering of cell-salvaged blood - does it make autotransfusion safer? Transfus Altern Transfus Med. 2012 Dec 1;12(3-4):78-87. doi: 10.1111/j.1778-428X.2012.01155.x. No abstract available. **PMID:** 24955005 **Citation:** Westerberg M, Gabel J, Bengtsson A, Sellgren J, Eidem O, Jeppsson A. Hemodynamic effects of cardiotomy suction blood. J Thorac Cardiovasc Surg. 2006 Jun;131(6):1352-7. doi: 10.1016/j.jtcvs.2005.12.067. **PMID:** 16733169 **Citation:** Gabel J, Westerberg M, Bengtsson A, Jeppsson A. Cell salvage of cardiotomy suction blood improves the balance between pro- and anti-inflammatory cytokines after cardiac surgery. Eur J Cardiothorac Surg. 2013 Sep;44(3):506-11. doi: 10.1093/ejcts/ezt019. Epub 2013 Feb 12. **PMID:** 23404689 **Citation:** Yasukawa T, Manabe S, Hiraoka D, Hirayama D, Kinoshita R, Komori M, Hosokawa M, Hirooka K. Safety and efficacy of a simple cardiotomy suction system as a blood salvage procedure during off-pump coronary artery bypass surgery. J Artif Organs. 2019 Sep;22(3):194-199. doi: 10.1007/s10047-019-01103-9. Epub 2019 Apr 9. **PMID:** 30968273 **Citation:** Vu T, Smith JA. An Update on Postoperative Cognitive Dysfunction Following Cardiac Surgery. Front Psychiatry. 2022 Jun 15;13:884907. doi: 10.3389/fpsyt.2022.884907. eCollection 2022. **PMID:** 35782418 **Citation:** Dabrowski W, Rzecki Z, Czajkowski M, Pilat J, Wacinski P, Kotlinska E, Sztanke M, Sztanke K, Stazka K, Pasternak K. Volatile anesthetics reduce biochemical markers of brain injury and brain magnesium disorders in patients undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2012 Jun;26(3):395-402. doi: 10.1053/j.jvca.2011.10.014. Epub 2011 Dec 28. **PMID:** 22206712 **Citation:** Allen SJ, McBride WT, McMurray TJ, Phillips AS, Penugonda SP, Campalani G, Young IS, Armstrong MA. Cell salvage alters the systemic inflammatory response after off-pump coronary artery bypass grafting surgery. Ann Thorac Surg. 2007 Feb;83(2):578-85. doi: 10.1016/j.athoracsur.2006.09.041. **PMID:** 17257991 **Citation:** Baker RA, Merry AF. Cell salvage is beneficial for all cardiac surgical patients: arguments for and against. J Extra Corpor Technol. 2012 Mar;44(1):P38-41. **PMID:** 22730871 **Citation:** Cote CL, Yip AM, MacLeod JB, O'Reilly B, Murray J, Ouzounian M, Brown CD, Forgie R, Pelletier MP, Hassan A. Efficacy of intraoperative cell salvage in decreasing perioperative blood transfusion rates in first-time cardiac surgery patients: a retrospective study. Can J Surg. 2016 Sep;59(5):330-6. doi: 10.1503/cjs.002216. **PMID:** 27668331 **Citation:** Engels GE, van Klarenbosch J, Gu YJ, van Oeveren W, de Vries AJ. Intraoperative cell salvage during cardiac surgery is associated with reduced postoperative lung injury. Interact Cardiovasc Thorac Surg. 2016 Mar;22(3):298-304. doi: 10.1093/icvts/ivv355. Epub 2015 Dec 23. **PMID:** 26705299 **Citation:** Izzat MB, Almohammad F, Raslan AF. Off-pump grafting does not reduce postoperative pulmonary dysfunction. Asian Cardiovasc Thorac Ann. 2017 Feb;25(2):113-117. doi: 10.1177/0218492316689350. Epub 2017 Jan 13. **PMID:** 28084083 **Citation:** Wan IY, Arifi AA, Wan S, Yip JH, Sihoe AD, Thung KH, Wong EM, Yim AP. Beating heart revascularization with or without cardiopulmonary bypass: evaluation of inflammatory response in a prospective randomized study. J Thorac Cardiovasc Surg. 2004 Jun;127(6):1624-31. doi: 10.1016/j.jtcvs.2003.10.043. **PMID:** 15173716 **Citation:** Kim KI, Lee WY, Ko HH, Kim HS, Jeong JH. Hemoglobin Level to Facilitate Off-Pump Coronary Artery Bypass without Transfusion. Korean J Thorac Cardiovasc Surg. 2014 Aug;47(4):350-7. doi: 10.5090/kjtcs.2014.47.4.350. Epub 2014 Aug 5. **PMID:** 25207243 **Citation:** Kitano T, Hattori S, Miyakawa H, Yoshitake S, Iwasaka H, Noguchi T. Unwashed shed blood infusion causes deterioration in right ventricular function after coronary artery surgery. Anaesth Intensive Care. 2000 Dec;28(6):642-5. doi: 10.1177/0310057X0002800605. **PMID:** 11153289 **Citation:** Munoz M, Slappendel R, Thomas D. Laboratory characteristics and clinical utility of post-operative cell salvage: washed or unwashed blood transfusion? Blood Transfus. 2011 Jul;9(3):248-61. doi: 10.2450/2010.0063-10. Epub 2010 Sep 14. No abstract available. **PMID:** 21084005 **Citation:** Murphy GJ, Rogers CS, Lansdowne WB, Channon I, Alwair H, Cohen A, Caputo M, Angelini GD. Safety, efficacy, and cost of intraoperative cell salvage and autotransfusion after off-pump coronary artery bypass surgery: a randomized trial. J Thorac Cardiovasc Surg. 2005 Jul;130(1):20-8. doi: 10.1016/j.jtcvs.2004.12.006. **PMID:** 15999036 **Citation:** Roman MA, Abbasciano RG, Pathak S, Oo S, Yusoff S, Wozniak M, Qureshi S, Lai FY, Kumar T, Richards T, Yao G, Estcourt L, Murphy GJ. Patient blood management interventions do not lead to important clinical benefits or cost-effectiveness for major surgery: a network meta-analysis. Br J Anaesth. 2021 Jan;126(1):149-156. doi: 10.1016/j.bja.2020.04.087. Epub 2020 Jun 30. **PMID:** 32620259 **Citation:** Wan S, Izzat MB, Lee TW, Wan IY, Tang NL, Yim AP. Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury. Ann Thorac Surg. 1999 Jul;68(1):52-6; discussion 56-7. doi: 10.1016/s0003-4975(99)00315-x. **PMID:** 10421114 **Citation:** Vieira SD, da Cunha Vieira Perini F, de Sousa LCB, Buffolo E, Chaccur P, Arrais M, Jatene FB. Autologous blood salvage in cardiac surgery: clinical evaluation, efficacy and levels of residual heparin. Hematol Transfus Cell Ther. 2021 Jan-Mar;43(1):1-8. doi: 10.1016/j.htct.2019.08.005. Epub 2019 Nov 7. **PMID:** 31791879 **Citation:** Wozniak MJ, Sullo N, Qureshi S, Dott W, Cardigan R, Wiltshire M, Morris T, Nath M, Bittar N, Bhudia SK, Kumar T, Goodall AH, Murphy GJ. Randomized trial of red cell washing for the prevention of transfusion-associated organ injury in cardiac surgery. Br J Anaesth. 2017 May 1;118(5):689-698. doi: 10.1093/bja/aex083. **PMID:** 28475670 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003327 - Term: Coronary Disease - ID: D000017202 - Term: Myocardial Ischemia - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000001161 - Term: Arteriosclerosis - ID: D000001157 - Term: Arterial Occlusive Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000006402 - Term: Hematologic Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M6549 - Name: Coronary Disease - Relevance: LOW - As Found: Unknown - ID: M6546 - Name: Coronary Artery Disease - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M19506 - Name: Myocardial Ischemia - Relevance: LOW - As Found: Unknown - ID: M30490 - Name: Transfusion Reaction - Relevance: HIGH - As Found: Blood Transfusion Complication - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M4469 - Name: Arteriosclerosis - Relevance: LOW - As Found: Unknown - ID: M4465 - Name: Arterial Occlusive Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003324 - Term: Coronary Artery Disease - ID: D000065227 - Term: Transfusion Reaction ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03036579 **Brief Title:** Celtra Duo Computer Assisted Design/Computer Assisted Machining (CAD/CAM) Dental Crown Study **Official Title:** Clinical Evaluation of Chairside Computer Assisted Design/Computer Assisted Machining (CAD/CAM) Zirconia-reinforced Lithium Silicate Ceramic Crowns #### Organization Study ID Info **ID:** HUM00103921 #### Organization **Class:** OTHER **Full Name:** University of Michigan ### Status Module #### Completion Date **Date:** 2019-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-04-13 **Type:** ACTUAL **Last Update Submit Date:** 2023-03-23 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2019-09 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-04-13 **Type:** ACTUAL **Results First Submit Date:** 2023-01-23 **Results First Submit QC Date:** 2023-03-23 #### Start Date **Date:** 2015-11 **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2017-01-30 **Type:** ESTIMATED **Study First Submit Date:** 2017-01-26 **Study First Submit QC Date:** 2017-01-26 **Why Stopped:** COVID, loss of funding ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Dentsply Sirona Inc. #### Lead Sponsor **Class:** OTHER **Name:** University of Michigan #### Responsible Party **Investigator Affiliation:** University of Michigan **Investigator Full Name:** Dennis J. Fasbinder, DDS **Investigator Title:** Clinical Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This investigation will be a clinical trial to study the performance of a newly developed high strength ceramic material for crowns. The ceramic has been approved by the FDA for patient treatment. A computer technique will be used to fabricate the crowns in a single appointment without the need for a temporary crown or second appointment. Two adhesive resin cement techniques will be used to hold the crown to the tooth and they will be evaluated for creating sensitivity to the tooth. The purpose of the study is to measure how well the high strength crowns function over an extended period of time. **Detailed Description:** The study will be composed of two groups of 50 crowns placed in adult patients that have been identified as requiring at least one crown on a posterior tooth. A maximum of two crowns per patient will be completed. All the crowns will be made from the same high strength ceramic material (Celtra Duo/Dentsply Sirona). The two groups of crowns will be made using two different processes to create the surface texture and finish for the crown. One group of Celtra Duo crowns (Group 1) will be glaze-fired in a porcelain oven and the second group (Group 2) will be hand-polished. All the crowns will be cemented using two adhesive techniques. All of the oven-fired, glazed crowns will be cemented using the self-etching, self-adhesive resin cement technique (Calibra Universal Cement/Dentsply). All of the hand polished crowns will be cemented using an adhesive bonding technique using Prime \& Bond Elect (Dentsply) with a dual cured resin cement (Calibra Ceram/Dentsply). The crowns are planned to be evaluated at 6 months, 1 year, 2 years, 3 years, and if funding permits, 4 years, and 5 years. At each appointment an examination of the crown will be completed as well as clinical photographs, an intraoral digital scan, and impression of the crown. ### Conditions Module **Conditions:** - Fractured Tooth - Decayed Tooth - Unsatisfactory Restoration of Tooth **Keywords:** - CAD/CAM - Ceramic - Crown ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Masking Description:** Final surface fabrication was not identified in the treatment process until the crown was milled. **Who Masked:** - CARE_PROVIDER **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 73 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Celtra Duo crowns will be glaze-fired in a porcelain oven and cemented with Calibra Ceram Cement **Intervention Names:** - Device: Celtra Duo **Label:** Glazed Fired, Calibra Céram **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Celtra Duo crowns will be hand-polished and cemented with Calibra Universal Cement **Intervention Names:** - Device: Celtra Duo **Label:** Hand Polished, Calibra Universal **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Glazed Fired, Calibra Céram - Hand Polished, Calibra Universal **Description:** Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **Name:** Celtra Duo **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Crown failure includes fracture of the crown or loss of the crown requiring placement of a new crown at any time between delivery and three years. **Measure:** Crown Failure **Time Frame:** from delivery of the crown up to 3 years #### Secondary Outcomes **Description:** Loss of retention is measured as detachment of the crown from the tooth without fracture of the crown requiring recementation of the crown. **Measure:** Crown Loss of Retention **Time Frame:** 3 years **Description:** Tooth Sensitivity is evaluated as either "0" if the subject reports that there is NO sensitivity for the tooth with the study crown, or "1" if the subject reports that there IS tooth sensitivity to hot/cold or biting pressure. The better outcome is to have NO tooth sensitivity. The number of teeth with tooth sensitivity are listed below. **Measure:** Tooth Sensitivity **Time Frame:** 3 years **Description:** Margin Staining is evaluated as either "0" if there is NO staining at the crown margin where it meets the tooth, or "1" if there IS staining at the crown margin where it meets the tooth. The better outcome is to have NO margin staining. The number of teeth with margin staining are listed below. **Measure:** Margin Staining **Time Frame:** from delivery of the crown up to 3 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * must have at least one carious lesion or defective restoration or fractured tooth in a molar or premolar * reason for restoration should extend more than one-half the intercuspal width of the tooth requiring a full crown restoration * Teeth to be vital and asymptomatic prior to treatment * No more than two restorations will be placed per patient. If a patient presents with more than two acceptable teeth for the study, molar teeth will be included prior to premolar teeth. Exclusion Criteria: * Devital or sensitive teeth * Teeth with prior endodontic treatment of any kind * Teeth with a history of direct or indirect pulp capping procedures * Patients with significant untreated dental disease to include periodontitis and rampant caries * Pregnant or lactating women * Patients with a history of allergies to any of the materials to be used in the study * Patients unable to return for the recall appointments **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Ann Arbor **Country:** United States **Facility:** University of Michigan **State:** Michigan **Zip:** 48109 #### Overall Officials **Official 1:** **Affiliation:** University of Michigan **Name:** Dennis J Fasbinder, DDS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2022-05-19 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 341562 - Type Abbrev: Prot_SAP - Upload Date: 2023-01-19T13:28 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014947 - Term: Wounds and Injuries - ID: D000017001 - Term: Tooth Demineralization - ID: D000014076 - Term: Tooth Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000018677 - Term: Tooth Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M6928 - Name: Dental Caries - Relevance: HIGH - As Found: Decayed Teeth - ID: M26370 - Name: Fractures, Bone - Relevance: LOW - As Found: Unknown - ID: M16837 - Name: Tooth Fractures - Relevance: HIGH - As Found: Fractured Tooth - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M19339 - Name: Tooth Demineralization - Relevance: LOW - As Found: Unknown - ID: M16831 - Name: Tooth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: M20757 - Name: Tooth Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003731 - Term: Dental Caries - ID: D000014082 - Term: Tooth Fractures ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M19022 - Name: Lithium Carbonate - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Glazed Fired, Calibra Céram **Deaths Num At Risk:** 41 **Description:** Celtra Duo crowns will be glaze-fired in a porcelain oven and cemented with Calibra Ceram Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** EG000 **Other Num at Risk:** 41 **Serious Number At Risk:** 41 **Title:** Glazed Fired, Calibra Céram **Group ID:** EG001 **Title:** Hand Polished, Calibra Universal **Deaths Num At Risk:** 32 **Description:** Celtra Duo crowns will be hand-polished and cemented with Calibra Universal Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** EG001 **Other Num at Risk:** 32 **Serious Number At Risk:** 32 **Title:** Hand Polished, Calibra Universal **Frequency Threshold:** 0 **Time Frame:** from baseline to 3 years ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 41 **Group ID:** BG001 **Value:** 32 **Group ID:** BG002 **Value:** 73 **Units:** Participants **Group ID:** BG000 **Value:** 50 **Group ID:** BG001 **Value:** 50 **Group ID:** BG002 **Value:** 100 **Units:** number of teeth restored with crowns ### Group **ID:** BG000 **Title:** Glazed Fired, Calibra Céram **Description:** Celtra Duo crowns will be glaze-fired in a porcelain oven and cemented with Calibra Ceram Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. ### Group **ID:** BG001 **Title:** Hand Polished, Calibra Universal **Description:** Celtra Duo crowns will be hand-polished and cemented with Calibra Universal Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 26 #### Measurement **Group ID:** BG001 **Value:** 23 #### Measurement **Group ID:** BG002 **Value:** 49 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 9 #### Measurement **Group ID:** BG002 **Value:** 24 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG002 **Value:** 0 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Description:** Age data not collected from any participant **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Age data not collected from any participant **Title:** Age, Customized **Unit of Measure:** Participants #### Denomination 1 ##### Denomination Count 1 **Group ID:** BG000 **Value:** 0 ##### Denomination Count 2 **Group ID:** BG001 **Value:** 0 ##### Denomination Count 3 **Group ID:** BG002 **Value:** 0 **Units:** Participants #### Denomination 2 ##### Denomination Count 1 **Group ID:** BG000 **Value:** 50 ##### Denomination Count 2 **Group ID:** BG001 **Value:** 50 ##### Denomination Count 3 **Group ID:** BG002 **Value:** 100 **Units:** number of teeth restored with crowns ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants #### Denomination 1 ##### Denomination Count 1 **Group ID:** BG000 **Value:** 41 ##### Denomination Count 2 **Group ID:** BG001 **Value:** 32 ##### Denomination Count 3 **Group ID:** BG002 **Value:** 73 **Units:** Participants #### Denomination 2 ##### Denomination Count 1 **Group ID:** BG000 **Value:** 50 ##### Denomination Count 2 **Group ID:** BG001 **Value:** 50 ##### Denomination Count 3 **Group ID:** BG002 **Value:** 100 **Units:** number of teeth restored with crowns ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Race and Ethnicity were not collected from any participant. **Title:** Race and Ethnicity Not Collected **Unit of Measure:** Participants #### Denomination 1 ##### Denomination Count 1 **Group ID:** BG000 **Value:** 0 ##### Denomination Count 2 **Group ID:** BG001 **Value:** 0 ##### Denomination Count 3 **Group ID:** BG002 **Value:** 0 **Units:** Participants #### Denomination 2 ##### Denomination Count 1 **Group ID:** BG000 **Value:** 50 ##### Denomination Count 2 **Group ID:** BG001 **Value:** 50 ##### Denomination Count 3 **Group ID:** BG002 **Value:** 100 **Units:** number of teeth restored with crowns **Population Description:** Number of teeth restored with crowns **Type Units Analyzed:** number of teeth restored with crowns ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** University of Michigan **Phone:** 7346474450 **Title:** Dennis J. Fasbinder, DDS ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Crown failure includes fracture of the crown or loss of the crown requiring placement of a new crown at any time between delivery and three years. **Parameter Type:** NUMBER **Population Description:** teeth restored with crowns **Reporting Status:** POSTED **Time Frame:** from delivery of the crown up to 3 years **Title:** Crown Failure **Type:** PRIMARY **Type Units Analyzed:** Teeth **Unit of Measure:** crowns ##### Group **Description:** Celtra Duo crowns will be glaze-fired in a porcelain oven and cemented with Calibra Ceram Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** OG000 **Title:** Glazed Fired, Calibra Céram ##### Group **Description:** Celtra Duo crowns will be hand-polished and cemented with Calibra Universal Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** OG001 **Title:** Hand Polished, Calibra Universal #### Outcome Measure 2 **Description:** Loss of retention is measured as detachment of the crown from the tooth without fracture of the crown requiring recementation of the crown. **Parameter Type:** NUMBER **Population Description:** number of crowns **Reporting Status:** POSTED **Time Frame:** 3 years **Title:** Crown Loss of Retention **Type:** SECONDARY **Type Units Analyzed:** Teeth **Unit of Measure:** crowns ##### Group **Description:** Celtra Duo crowns will be glaze-fired in a porcelain oven and cemented with Calibra Ceram Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** OG000 **Title:** Glazed Fired, Calibra Céram ##### Group **Description:** Celtra Duo crowns will be hand-polished and cemented with Calibra Universal Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** OG001 **Title:** Hand Polished, Calibra Universal #### Outcome Measure 3 **Description:** Tooth Sensitivity is evaluated as either "0" if the subject reports that there is NO sensitivity for the tooth with the study crown, or "1" if the subject reports that there IS tooth sensitivity to hot/cold or biting pressure. The better outcome is to have NO tooth sensitivity. The number of teeth with tooth sensitivity are listed below. **Parameter Type:** NUMBER **Population Description:** number of teeth with crown **Reporting Status:** POSTED **Time Frame:** 3 years **Title:** Tooth Sensitivity **Type:** SECONDARY **Type Units Analyzed:** Teeth **Unit of Measure:** Teeth ##### Group **Description:** Celtra Duo crowns will be glaze-fired in a porcelain oven and cemented with Calibra Ceram Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** OG000 **Title:** Glazed Fired, Calibra Céram ##### Group **Description:** Celtra Duo crowns will be hand-polished and cemented with Calibra Universal Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** OG001 **Title:** Hand Polished, Calibra Universal #### Outcome Measure 4 **Description:** Margin Staining is evaluated as either "0" if there is NO staining at the crown margin where it meets the tooth, or "1" if there IS staining at the crown margin where it meets the tooth. The better outcome is to have NO margin staining. The number of teeth with margin staining are listed below. **Parameter Type:** NUMBER **Population Description:** number of crowns **Reporting Status:** POSTED **Time Frame:** from delivery of the crown up to 3 years **Title:** Margin Staining **Type:** SECONDARY **Type Units Analyzed:** Teeth **Unit of Measure:** crowns ##### Group **Description:** Celtra Duo crowns will be glaze-fired in a porcelain oven and cemented with Calibra Ceram Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** OG000 **Title:** Glazed Fired, Calibra Céram ##### Group **Description:** Celtra Duo crowns will be hand-polished and cemented with Calibra Universal Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** OG001 **Title:** Hand Polished, Calibra Universal ### Participant Flow Module #### Group **Description:** Celtra Duo crowns will be glaze-fired in a porcelain oven and cemented with Calibra Ceram Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** FG000 **Title:** Glazed Fired, Calibra Céram #### Group **Description:** Celtra Duo crowns will be hand-polished and cemented with Calibra Universal Cement Celtra Duo: Full ceramic crowns will be made from the high strength ceramic, Celtra Duo. **ID:** FG001 **Title:** Hand Polished, Calibra Universal #### Period **Title:** Baseline ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Number of Units:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Number of Units:** 0 #### Period **Title:** 6 Months ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Number of Units:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Number of Units:** 0 #### Period **Title:** 1 Year ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Number of Units:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Number of Units:** 0 #### Period **Title:** 2 Years ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 40 **Number of Units:** 49 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 **Number of Units:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Number of Units:** 0 #### Period **Title:** 3 Years ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 **Number of Units:** 50 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 41 **Number of Units:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 31 **Number of Units:** 49 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Number of Units:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 1 **Number of Units:** 1 **Pre-Assignment Details:** Recall at 5 years not funded by sponsor, therefore data not collected up to 5 years **Type Units Analyzed:** tooth **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT03288779 **Brief Title:** Theta Burst Stimulation for Schizophrenia **Official Title:** Theta Burst Stimulation for Schizophrenia #### Organization Study ID Info **ID:** Pro00083070 #### Organization **Class:** OTHER **Full Name:** Duke University ### Status Module #### Completion Date **Date:** 2018-06-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-11-25 **Type:** ACTUAL **Last Update Submit Date:** 2019-11-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-06-30 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-11-25 **Type:** ACTUAL **Results First Submit Date:** 2019-06-20 **Results First Submit QC Date:** 2019-11-06 #### Start Date **Date:** 2017-10-24 **Type:** ACTUAL **Status Verified Date:** 2019-08 #### Study First Post Date **Date:** 2017-09-20 **Type:** ACTUAL **Study First Submit Date:** 2017-09-18 **Study First Submit QC Date:** 2017-09-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Duke University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Purpose and objective Schizophrenia is a chronic debilitating illness with cognitive deficits that cause serious impairment in psychosocial recovery and with few treatments to remediate these deficits. One area that holds great promise for the development of novel, effective therapies is noninvasive brain stimulation. The investigators have used one form of brain stimulation, transcranial magnetic stimulation (TMS), for some time to modulate and enhance cognitive function in the brain, especially working memory (WM) function, which has a central role in most executive processing that occurs in the brain. Theta burst stimulation (TBS) is a paradigm of TMS which has been shown to effectively modulate WM. Moreover, TBS can modulate gamma neural oscillations in the brain and neural activity, both of which have been implicated in the physiology of WM and pathophysiology of the disease process in schizophrenia, making these measures highly valuable for assessing physiological effects of TBS on cognition, quality of life and cortical inhibition. The purpose of this study is to evaluate the effect of TBS on WM in patients with schizophrenia, to develop evidence for potential brain stimulation techniques to treat cognitive deficits in schizophrenia. Study activities and population group: Study subjects will be inpatient schizophrenic individuals with minimal positive symptoms and predominant cognitive deficits at Duke University Hospital. In an initial session they will be screened and taught a WM task. Following this, one TBS session will follow in which TBS will target dorsolateral prefrontal cortex. They will perform the WM task before, with and after the TBS, with an expected pre-post enhancement of WM performance. Implications - There is a great need for treatments for cognitive deficits in schizophrenia. The results of this study will serve to generate pilot data for a much larger grant to develop a TBS therapy for remediating such cognitive deficits. **Detailed Description:** Purpose of the study Aim1: Evaluate the effect of theta burst stimulation (TBS) on working memory (WM) in patients with schizophrenia. Hypothesis 1 - There will be significant improvement in WM compared to baseline with one session of TBS. Background and Significance Schizophrenia is an illness known to have cognitive deficits, with a chronic and variable course. There is extensive research on cognitive deficits, with working memory, processing speed and verbal memory being some of the domains affected. Some modalities of treatment that have been tried to reverse these cognitive deficits are medications and cognitive behavioral therapy with minimal benefits. A few studies have shown modulation of working memory with routine repetitive transcranial magnetic stimulation at frequencies not exceeding 10 to 20 Hz of stimulation. Other studies have shown the working memory to be related to gamma oscillations. A few studies have also shown that transcranial magnetic stimulation (TMS) modulates these gamma oscillations as well. There is an extensive body of literature that shows that working memory has contributions from theta and gamma oscillations in the brain. Theta burst stimulation (TBS) is a form of transcranial magnetic stimulation (TMS), that entrains gamma and theta frequencies in the brain. It could be the most appropriate form of brain stimulation for improving cognition in schizophrenia patients because it has been shown to modulate brain oscillations in small samples of patients. The area for targeting would be the dorsolateral prefrontal cortex which is the site of origin of the gamma oscillations and plays a significant role in working memory. Design and Procedures The study is designed to be a pilot one evaluating the effect of TBS on WM in patients with schizophrenia. The investigators plan to screen 20 subjects to have 10 participants. Working memory will be tested using delayed match sample task (DMS) and brief assessment of cognition in schizophrenia battery (BACS). Transcranial Magnetic Stimulation (TMS) administration The patient would be transported from the inpatient unit to the TMS lab following screening and consent process. They would be accompanied by nursing staff. During their visit to the TMS lab a sample TMS session including motor threshold determination will be conducted. Subjects would be allowed to practice the DMS task to allow for the ceiling in practice effect of the task. The BACS would be administered before and after the TMS session. Treatment Sessions Subjects would be administered left sided theta burst stimulation (TBS).The subject will be seated in a chair. A 64-channel electrode cap may be applied to the head for EEG recording. Electromyogram (EMG) electrodes will be applied to the right hand for motor evoked potential (MEP) recording. Subjects will perform the DMS task while sitting in the chair during the TMS session. EEG and EMG will be recorded throughout the treatment sessions. For theta burst stimulation the active motor threshold would be 80 % as used in most theta burst studies detailed in this review. Subjects would receive theta burst stimulation comprising 50 Hz bursts given at 3 to 5 Hz for close to 10 minutes which comprises 60 trains and 1800 pulses. The subject will be monitored until MEPs return to baseline. A side effects checklist will be completed at the beginning and at the end of the experimental session. All sessions will be performed by one of the protocol investigators, or by a trained and accredited research assistant supervised by the protocol investigators. Clinical and cognitive assessments/tasks PANSS The Positive and negative symptoms scale is used to assess the severity of schizophrenia. It has three subscales - positive, negative and general psychopathology. Each of these subscales had 7 items, the maximum scores on each of these subscales in 49, minimum score being 7. DMS task The DMS task is a modified version of the Sternberg task and has been adapted for use in cognitive paradigms accompanying transcranial magnetic stimulation. Each trial will last 13 s, with the following sequence of three task stages: encoding, retention and probe stages. BACS - Tasks to be done from the actual BACS battery of tests List Learning (Verbal Memory). Patients are presented with 15 words and then asked to recall as many as possible. This procedure is repeated 5 times. There are two alternate forms. Digit Sequencing Task (verbal working Memory). Patients are presented with clusters of numbers of increasing length. They are asked to tell the experimenter the numbers in order, from lowest to highest. Token Motor Task (Motor Speed). Patients are given 100 plastic tokens and asked to place them into a container as quickly as possible for 60 seconds. Verbal Fluency. Tests of Category Instances (Semantic Fluency) and Controlled Oral Word Association Test (Letter Fluency) are administered. Patients are given 60 seconds to name as many words as possible within a given semantic category, and in two separate trials, patients are given 60 seconds to generate as many words as possible that begin with a given letter. The total number of words from the three trials is the outcome measure. Tower of London (Reasoning and Problem Solving). Patients look at two pictures simultaneously. Each picture shows 3 different-colored balls arranged on 3 pegs, with the balls in a unique arrangement in each picture. The patients are told about the rules in the task and are asked to provide the least number of times the balls in one picture would have to be moved to make the arrangement of balls identical to that of the other, opposing picture. There are two alternate forms. Symbol Coding (Attention and Processing Speed). As quickly as possible, patients write numerals 1-9 as matches to symbols on a response sheet for 90 seconds. Each of the six measures are compared to a healthy control sample to create z-scores, and a composite score is calculated by summing these z-scores and calculating a z-score of that sum. The composite score has high test-retest reliability in patients with schizophrenia and healthy controls (ICCs \> .80). ### Conditions Module **Conditions:** - Schizophrenia - Schizoaffective Disorder ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 6 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This is a pilot open label study. **Intervention Names:** - Device: Theta Burst Stimulation **Label:** Theta Burst Stimulation Arm **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Theta Burst Stimulation Arm **Description:** Transcranial magnetic stimulation with theta burst stimulation **Name:** Theta Burst Stimulation **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Performance on tasks included in the Brief Assessment of Cognition in Schizophrenia (BACS) battery, task performed and results recorded on IPAD. The mean change from baseline in total cognitive score on the BACS was calculated as a weighted average of T-scores (normalized for age) from BACS subtests including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Semantic Fluency, Letter Fluency, and Tower of London. The minimum and maximum values possible for this composite T-score of the change from baseline were -131 and 131, respectively. Higher values (positive changes from baseline) indicate better performance. **Measure:** Brief Assessment of Cognition (BACS) Composite T Score **Time Frame:** 30 minutes #### Secondary Outcomes **Measure:** Change in Gamma and Theta Oscillations as Measured by EEG **Time Frame:** one session, approximately 30 minutes ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients aged 18-65 years of age with schizophrenia or schizoaffective disorder * No other mental health diagnoses * Right handed males and females * May have mild positive symptoms (score of \</= 21) * May have negative symptoms * Ability to provide informed consent * No restriction on concomitant medications given Exclusion Criteria: * Intellectual disability * Any organic brain illness Presence of dementia symptoms or traumatic brain injury Primary diagnosis of substance use Seizure disorder Actively symptomatic with PANSS positive symptom sub-scale \>21. Concurrently receiving electroconvulsive therapy (ECT) **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Durham **Country:** United States **Facility:** Duke University Medical Center **State:** North Carolina **Zip:** 27710 #### Overall Officials **Official 1:** **Affiliation:** Duke University **Name:** Gopalkumar Rakesh, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Green MF, Nuechterlein KH, Gold JM, Barch DM, Cohen J, Essock S, Fenton WS, Frese F, Goldberg TE, Heaton RK, Keefe RS, Kern RS, Kraemer H, Stover E, Weinberger DR, Zalcman S, Marder SR. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry. 2004 Sep 1;56(5):301-7. doi: 10.1016/j.biopsych.2004.06.023. **PMID:** 15336511 **Citation:** Keefe RS, Fox KH, Harvey PD, Cucchiaro J, Siu C, Loebel A. Characteristics of the MATRICS Consensus Cognitive Battery in a 29-site antipsychotic schizophrenia clinical trial. Schizophr Res. 2011 Feb;125(2-3):161-8. doi: 10.1016/j.schres.2010.09.015. Epub 2010 Dec 31. **PMID:** 21075600 **Citation:** Young JW, Geyer MA. Developing treatments for cognitive deficits in schizophrenia: the challenge of translation. J Psychopharmacol. 2015 Feb;29(2):178-96. doi: 10.1177/0269881114555252. Epub 2014 Dec 16. **PMID:** 25516372 **Citation:** Barr MS, Farzan F, Arenovich T, Chen R, Fitzgerald PB, Daskalakis ZJ. The effect of repetitive transcranial magnetic stimulation on gamma oscillatory activity in schizophrenia. PLoS One. 2011;6(7):e22627. doi: 10.1371/journal.pone.0022627. Epub 2011 Jul 27. **PMID:** 21818354 **Citation:** Farzan F, Barr MS, Sun Y, Fitzgerald PB, Daskalakis ZJ. Transcranial magnetic stimulation on the modulation of gamma oscillations in schizophrenia. Ann N Y Acad Sci. 2012 Aug;1265:25-35. doi: 10.1111/j.1749-6632.2012.06543.x. Epub 2012 Jul 23. **PMID:** 22823464 **Citation:** Hasan A, Brinkmann C, Strube W, Palm U, Malchow B, Rothwell JC, Falkai P, Wobrock T. Investigations of motor-cortex cortical plasticity following facilitatory and inhibitory transcranial theta-burst stimulation in schizophrenia: a proof-of-concept study. J Psychiatr Res. 2015 Feb;61:196-204. doi: 10.1016/j.jpsychires.2014.12.006. Epub 2014 Dec 19. Erratum In: J Psychiatr Res. 2016 Sep;80:1-2. **PMID:** 25555304 **Citation:** Tikka SK, Nizamie SH, Venkatesh Babu GM, Aggarwal N, Das AK, Goyal N. Safety and Efficacy of Adjunctive Theta Burst Repetitive Transcranial Magnetic Stimulation to Right Inferior Parietal Lobule in Schizophrenia Patients With First-Rank Symptoms: A Pilot, Exploratory Study. J ECT. 2017 Mar;33(1):43-51. doi: 10.1097/YCT.0000000000000343. **PMID:** 27428476 **Citation:** Demirtas-Tatlidede A, Freitas C, Cromer JR, Safar L, Ongur D, Stone WS, Seidman LJ, Schmahmann JD, Pascual-Leone A. Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia. Schizophr Res. 2010 Dec;124(1-3):91-100. doi: 10.1016/j.schres.2010.08.015. **PMID:** 20817483 **Citation:** Gonzalez-Burgos G, Cho RY, Lewis DA. Alterations in cortical network oscillations and parvalbumin neurons in schizophrenia. Biol Psychiatry. 2015 Jun 15;77(12):1031-40. doi: 10.1016/j.biopsych.2015.03.010. Epub 2015 Mar 17. **PMID:** 25863358 **Citation:** Barr MS, Farzan F, Rusjan PM, Chen R, Fitzgerald PB, Daskalakis ZJ. Potentiation of gamma oscillatory activity through repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex. Neuropsychopharmacology. 2009 Oct;34(11):2359-67. doi: 10.1038/npp.2009.79. Epub 2009 Jul 15. **PMID:** 19606086 **Citation:** Keefe RS, Poe M, Walker TM, Harvey PD. The relationship of the Brief Assessment of Cognition in Schizophrenia (BACS) to functional capacity and real-world functional outcome. J Clin Exp Neuropsychol. 2006 Feb;28(2):260-9. doi: 10.1080/13803390500360539. **PMID:** 16484097 ## Document Section ### Large Document Module #### Large Docs - Date: 2018-05-04 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 992292 - Type Abbrev: Prot_SAP - Upload Date: 2019-06-20T09:44 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019967 - Term: Schizophrenia Spectrum and Other Psychotic Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M15376 - Name: Schizophrenia - Relevance: HIGH - As Found: Schizophrenia - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: HIGH - As Found: Schizoaffective Disorder - ID: M21838 - Name: Schizophrenia Spectrum and Other Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012559 - Term: Schizophrenia - ID: D000011618 - Term: Psychotic Disorders ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Patients With a Diagnosis of Schizophrenia **Deaths Num At Risk:** 6 **Description:** We recruited 6 patients with diagnoses of schizophrenia. Inpatient subjects were recruited towards the latter half of their inpatient stay, after their positive symptoms had decreased in severity. PANSS was performed at recruitment and subjects were chosen for the study only if their positive symptom score was less than or equal to 21. Our other inclusion criteria for the study were patients in the age group of 18-50 years, right handed, with no other comorbid DSM-5 diagnoses (including substance use disorder), and able to give informed consent. Subjects with organic basis for their psychopathology or intellectual disability, were excluded from the study. **ID:** EG000 **Other Num at Risk:** 6 **Serious Number At Risk:** 6 **Title:** Patients With a Diagnosis of Schizophrenia **Frequency Threshold:** 0 **Time Frame:** 6 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 6 **Units:** Participants ### Group **ID:** BG000 **Title:** Patients With a Diagnosis of Schizophrenia **Description:** We recruited 6 patients with diagnoses of schizophrenia. Inpatient subjects were recruited towards the latter half of their inpatient stay, after their positive symptoms had decreased in severity. PANSS was performed at recruitment and subjects were chosen for the study only if their positive symptom score was less than or equal to 21. Our other inclusion criteria for the study were patients in the age group of 18-50 years, right handed, with no other comorbid DSM-5 diagnoses (including substance use disorder), and able to give informed consent. Subjects with organic basis for their psychopathology or intellectual disability, were excluded from the study. ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 6 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 7 **Value:** 33 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 4 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 4 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 6 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Spread:** 17.4 **Value:** 26.3 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Brief Assessment of Cognition (BACS) Composite T Score **Unit of Measure:** Composite T- Score ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** DukeUMC **Phone:** 3524540101 **Phone Extension:** 3524540101 **Title:** Steven T Szabo ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 18.5 - **Spread:** - **Upper Limit:** 56.1 - **Value:** 37.33 **Title:** #### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Performance on tasks included in the Brief Assessment of Cognition in Schizophrenia (BACS) battery, task performed and results recorded on IPAD. The mean change from baseline in total cognitive score on the BACS was calculated as a weighted average of T-scores (normalized for age) from BACS subtests including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Semantic Fluency, Letter Fluency, and Tower of London. The minimum and maximum values possible for this composite T-score of the change from baseline were -131 and 131, respectively. Higher values (positive changes from baseline) indicate better performance. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 30 minutes **Title:** Brief Assessment of Cognition (BACS) Composite T Score **Type:** PRIMARY **Unit of Measure:** Composite T- Score ##### Group **Description:** This is a pilot open label study. Theta Burst Stimulation: Transcranial magnetic stimulation with theta burst stimulation **ID:** OG000 **Title:** Theta Burst Stimulation Arm #### Outcome Measure 2 **Population Description:** No EEG data was collected **Reporting Status:** POSTED **Time Frame:** one session, approximately 30 minutes **Title:** Change in Gamma and Theta Oscillations as Measured by EEG **Type:** SECONDARY ##### Group **Description:** This is a pilot open label study. Theta Burst Stimulation: Transcranial magnetic stimulation with theta burst stimulation **ID:** OG000 **Title:** Theta Burst Stimulation Arm ### Participant Flow Module #### Group **Description:** We recruited 6 patients with diagnoses of schizophrenia. Inpatient subjects were recruited towards the latter half of their inpatient stay, after their positive symptoms had decreased in severity. PANSS was performed at recruitment and subjects were chosen for the study only if their positive symptom score was less than or equal to 21. Our other inclusion criteria for the study were patients in the age group of 18-50 years, right handed, with no other comorbid DSM-5 diagnoses (including substance use disorder), and able to give informed consent. Subjects with organic basis for their psychopathology or intellectual disability, were excluded from the study. Intervention administered - Theta Burst Stimulation (TBS) with Brief Assessment of Cognition in Schizophrenia (BACS) administered before and after TBS. **ID:** FG000 **Title:** Patients With a Diagnosis of Schizophrenia #### Period **Title:** Overall Study ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 6 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 **Recruitment Details:** We recruited 6 patients with diagnoses of schizophrenia, which included 4 inpatients and 2 outpatients. **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT06064279 **Acronym:** HAITEN-ICI **Brief Title:** Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC **Official Title:** Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC #### Organization Study ID Info **ID:** SPLP-002-23S #### Organization **Class:** FED **Full Name:** VA Office of Research and Development #### Secondary ID Infos **Domain:** VAMC **ID:** CSR&D **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2028-04-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-30 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-26 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-06-22 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-24 **Type:** ESTIMATED **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2023-10-03 **Type:** ACTUAL **Study First Submit Date:** 2023-09-01 **Study First Submit QC Date:** 2023-09-28 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Oncovir, Inc. #### Lead Sponsor **Class:** FED **Name:** VA Office of Research and Development #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Veterans with advanced lung cancer may benefit from recent advances in technologies that is designed to change the activities of their own white blood cells and help kill tumors. However, many cancers can hide from white blood cells making white blood cells less effective in killing tumors. In this study the investigators plan to boost the activity of patients white blood cell by making tumor cells more visible to the white blood cells. This will be done by injecting antibodies and a new drug that together can make white blood cells inside tumors more active. The investigators plan to recruit sixteen people with advanced lung cancer to make sure that this treatment, which has not been done in any humans, is safe and well tolerated. **Detailed Description:** This is a phase 1b, a first-in-humans, study to examine the safety and feasibility of administration of intratumor (IT) IVIG + poly-ICLC (Hiltonoll®), and intramuscular (IM) poly-ICLC (Hiltonoll®) for the treatment of advanced non-small cell lung cancer (NSCLC) in Veterans without targetable mutations. The investigators will employ the Bayesian optimal interval (BOIN) design 1, with dose escalation, de-escalation endpoints to find the maximum tolerated dose (MTD) in IT injections (IVIG + poly-ICLC) and IM poly-ICLC in 16 subjects while receiving front line Immune Checkpoint inhibitors (ICIs) as the standard of care (SOC). All patients continue to receive ICIs. If safe, a future phase II randomized-controlled study will be designed to determine if treatment with IT injections (IVIG + poly-ICLC) and IM injections (poly-ICLC) results in improved progression free survival. Primary Objective: To evaluate the safety and determine the MTD as assessed by Common Terminology Criteria for Adverse Events version 6 (CTCAE v. 6) of IT injection of IVIG + poly-ICLC, and IM poly-ICLC given in combination with ICI in Veterans with stage IV NSCLC. Secondary Objective: To quantitate systemic and tissue-specific immune responses in patients who receive intertumoral IVIG + poly-ICLC, and IM poly-ICLC while receiving ICIs. Primary Endpoint: Assessment of an MTD dose for IT injection of IVIG + poly-ICLC, and IM injection of poly-ICLC given in combination with ICI in patients with stage IV NSCLC. The primary safety endpoint includes short term and long-term dose limiting toxicity (DLT), and observing less than 25% grade 3 toxicity. Secondary Endpoints: 1) To assess the correlation of pre-therapy tumor PD-L1 expression with clinical benefit - All tumors will be assessed for PD-L1 expression prior to therapy initiation. 2) To determine the pre-treatment tumor immune infiltrate, and post treatment T cell activation, and correlation with treatment response. ### Conditions Module **Conditions:** - Stage IV NSCLC **Keywords:** - NSCLC, Immune Checkpoint inhibitor , PDL-1 ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 16 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with stage IV NSCLC will be treated with poly-ICLC + IVIG **Intervention Names:** - Drug: Poly ICLC - Drug: IVIG **Label:** Poly-ICLC + IVIG **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Poly-ICLC + IVIG **Description:** Tol like receptor 3 agonist **Name:** Poly ICLC **Other Names:** - Hiltonol **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Poly-ICLC + IVIG **Description:** pooled IVIG **Name:** IVIG **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Evaluate the safety as assessed by Common Terminology Criteria for Adverse Events version 6 (CTCAE v. 6) of IT injection of IVIG + poly-ICLC, and IM poly-ICLC given in combination with ICI in Veterans with stage IV NSCLC. **Measure:** Assessment of an MTD dose for IT injection of IVIG + poly-ICLC, and IM injection of poly-ICLC given in combination with ICI in patients with stage IV NSCLC. The primary safety endpoint includes short term and long-term dose limiting toxicity (DLT), and o **Time Frame:** Ten months #### Secondary Outcomes **Description:** To quantitate systemic immune responses in patients who receive intratumor IVIG + poly-ICLC, and IM poly-ICLC while receiving ICIs. Pt's adaptive immune cells (T cells) will be examined for the expression of activation markers before and after treatment. The correlation between % changes in immune cell activation and disease progression will be determined. **Measure:** To assess the percent of patients with increase PD-L1 expression and assess clinical outcome after treatment **Time Frame:** Ten months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Veterans with advanced (stage IV) NSCLC * Eligible to receive ICI/antiPD-1mAb * No known mutation actionable for first line treatment * An Eastern Cooperative Oncology Group (ECOG) performance-status (PS) score of 2 or less (ECOG PS is a 5-point scale in which higher scores reflect greater disability) * Veterans' responses will be defined as eligible to enroll in HAITEN-ICIs if they meet all criteria * To minimize the effects of immunosuppression on the ability to induce antitumor immunity, the investigators will recruit those who have not received systemic cytotoxic chemotherapy (e.g., platinum, taxane, pemetrexed, etc.), do not have major immunosuppression, and are not recipients of organ transplantation * Based on our patient population at the MEDVAMC, the investigators estimate that \~30-40% of participants would be receiving systemic chemotherapy and ICIs concurrently, and \~60-70% will be receiving ICI monotherapy * Therefore, the investigators anticipate no difficulty in meeting the recruitment goal of 16 persons at our center over two years and \~18 at each of the other sites over the 4-year study period Exclusion Criteria: Veterans with * Concurrent other malignancies, except for localized prostate or localized skin cancer * Uncontrolled rheumatologic diseases (such as rheumatoid arthritis) * Current usage of biologics or immunosuppressive therapies * Status post organ transplant * An acute respiratory illness (pneumonia, bronchitis, upper respiratory tract infection) in the preceding 4 weeks **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Farrah Kheradmand, MD **Phone:** (713) 791-1414 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Anita L Sabichi **Phone:** (713) 791-1414 **Role:** CONTACT #### Locations **Location 1:** **City:** Houston **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Farrah Kheradmand, MD - **Phone:** 713-791-1414 - **Role:** CONTACT ***Contact 2:*** - **Name:** Farrah Kheradmand, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Michael E. DeBakey VA Medical Center, Houston, TX **State:** Texas **Zip:** 77030-4211 #### Overall Officials **Official 1:** **Affiliation:** Michael E. DeBakey VA Medical Center, Houston, TX **Name:** Farrah Kheradmand, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR - ANALYTIC_CODE **IPD Sharing:** YES ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms - ID: D000008175 - Term: Lung Neoplasms - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: HIGH - As Found: NSCLC - ID: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M5260 - Name: Bronchial Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11172 - Name: Lung Neoplasms - Relevance: LOW - As Found: Unknown - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002289 - Term: Carcinoma, Non-Small-Cell Lung ### Intervention Browse Module - Ancestors - ID: D000007369 - Term: Interferon Inducers - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: LOW - As Found: Unknown - ID: M280480 - Name: Poly ICLC - Relevance: HIGH - As Found: Colchicine - ID: M10407 - Name: Interferons - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000019531 - Term: Poly ICLC ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04965779 **Brief Title:** The Effect of Abdominal Binder Use on Postpartum Pain, Bleeding, and Breastfeeding Success in Cesarean Delivery Women **Official Title:** The Effect of Abdominal Binder Use on Postpartum Pain, Bleeding, and Breastfeeding Success in Women Who Undergo Cesarean Delivery #### Organization Study ID Info **ID:** CukurovaUniversity_PK_01 #### Organization **Class:** OTHER **Full Name:** Cukurova University ### Status Module #### Completion Date **Date:** 2022-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-20 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-18 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2021-03-19 **Type:** ACTUAL #### Start Date **Date:** 2020-09-22 **Type:** ACTUAL **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2021-07-16 **Type:** ACTUAL **Study First Submit Date:** 2021-06-18 **Study First Submit QC Date:** 2021-07-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cukurova University #### Responsible Party **Investigator Affiliation:** Nigde Omer Halisdemir University **Investigator Full Name:** Kara Pınar **Investigator Title:** Research Asisstant **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this randomized controlled interventional study is to identify the effect of the use of an abdominal binder on postpartum pain, bleeding, and breastfeeding success in primiparous women who have undergone planned cesarean delivery with spinal anesthesia. **Detailed Description:** A 2015 report by the World Health Organization (WHO) has emphasized that cesarean section can be effective in preventing maternal and perinatal mortality and morbidity when there is a life-threatening danger to the mother and/or fetus, but provides no benefit to the woman or the baby otherwise. It also states that the ideal cesarean section rate 10% to 15%, and a rate above 10% at the population level is ineffective in decreasing maternal and infant mortality. However, current cesarean rates are much higher than recommended, especially in developed western countries, and rates ranging from 14.8% (Israel) to 54.8% (Turkey) have been reported as of 2018. Turkey, with a rate of 54.8%, has the highest cesarean section rate among the reported data. Cesarean delivery is common worldwide and presents many maternal and neonatal risks. While bleeding is the most serious of these risks, the women also experience severe pain and face problems with breastfeeding. The risk of a postpartum bleeding complication is reported to be 2.5 times higher in women who have undergone a planned cesarean section. The rate of experiencing any pain after a cesarean section has been reported as 77% to 92.7% while the incidence of moderate/severe pain is 15.2% to 52.2%. In addition, the probability of experiencing breastfeeding problems in the post-cesarean period is reported to be approximately 7 times higher. The need for optimum care in the postpartum period in order to protect the health of both the mother and the newborn, and also to prevent the health problems that may develop in the short and long term has been emphasized. Appropriate interventions of the nurses who are in close contact with the women, the newborns, and the families during the postpartum period affect the quality of care significantly. Based on this information, the various effects of the post-cesarean use of an abdominal binder, which is a noninvasive nursing intervention, has been evaluated in the literature and shown to have various benefits in the management of postpartum complications and problems after cesarean section in women with various characteristics. A limited number of studies have reported that the use of an abdominal binder decreases pain but inconsistent effect on postpartum bleeding. However, there is no study evaluating the effect of abdominal binder use on breastfeeding success. The study was planned as a randomized controlled interventional study with the women randomly divided into intervention (abdominal binder) and control groups. A preliminary application was used to determine the sample size of the study. Based on the power analysis performed with the data obtained, a total of 128 women were included in the study with 64 women in each group, at a confidence interval of 95%, power of 90%, and α level of 0.05. Block random sampling method was adopted to recruit participants. In order to randomly assign the participants to the groups, a list of 1:1 random numbers was created with the software Research Randomizer (https://www.randomizer.org/) on the computer. Participants were assigned to groups by 8-block randomization method. Randomization was done by an expert statistical consultant who was not responsible for conducting the study. The determined randomization number of list was printed out separately and sealed in each envelope. The random number was hidden in sealed envelopes until participants approved to participate in the study. Writing the random numbers on the papers, placing them in the envelopes and opening the paper in the sealed envelopes were done by an independent volunteer who was not responsible for the conduct of the study. Those who meet the inclusion and exclusion criteria and approve to participate in the study was allocated to intervention (abdominal binder) group or control group according to the result of randomization. In order to prevent bias each participant in the groups was followed in different rooms from the other participants in the group to which they were assigned. SPSS software (IBM Corp., Armonk, NY, v. 24.0) will be used to evaluate the data. Descriptive analysis will be calculated using mean and standard deviation, median and interquartile range for continuous variables, and percentage and frequency for categorical variables. Independent sample t-tests, Mann-Whitney U test, chi-square test or Fisher's exact test will be used to compare any differences in socio-demographic data or outcome variables between groups. To determine the differences or changes between study group and control group (between group effects), within group effects (time), and the interaction effects (group x time), repeated measures analysis of variances (RM-ANOVA) and to compare the variables with two repeated measurements paired sample t-test will be applied when assumptions for parametric test are fulfilled. When the data cannot fulfill the assumptions of parametric test, Mann-Whitney U test will be applied to compare the differences between groups at each time interval while Friedman test will be used to determine the time effects within each group. Significant results are indicated if p-value of all statistical analysis is less than 0.05 for two-tailed test. Tools for measuring the outcome variables in this study have been demonstrated validity and reliability (Breastfeeding Assesment Scale \[LATCH\]) and selectivity (Visual Analog Scale \[VAS\]) in Turkey. ### Conditions Module **Conditions:** - Cesarean Section **Keywords:** - Cesarean Section - Pain - Bleeding - Breast Feeding - Abdominal binder - Nursing postpartum care ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 128 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The abdominal binder is applied after the women come to the clinic (postpartum 1st hour) following cesarean delivery and removed after the postpartum 48th hour. Postpartum nursing care in line with a follow-up protocol that was created based on the Republic of Turkey Ministry of Health's Postpartum Care Management Guide (2018) is provided together with the application of the abdominal binder. **Intervention Names:** - Device: Abdominal Binder - Other: Postpartum nursing care **Label:** Intervention group (Abdominal binder) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Only postpartum nursing care in line with a follow-up protocol that was created based on the Republic of Turkey Ministry of Health's Postpartum Care Management Guide (2018) is provided with no abdominal binder or similar application. **Intervention Names:** - Other: Postpartum nursing care **Label:** Control group (No abdominal binder) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention group (Abdominal binder) **Description:** Women in the intervention group use an abdominal binder from postpartum hour 1 to 48, and will be checked every 6 hours. The abdominal circumference of the women is measured at the anterior superior iliac spine and umbilicus level with a tape measure before the application, and the binder size is adjusted to be 5% smaller (approximately 0.5-1 cm) than the measurement obtained. **Name:** Abdominal Binder **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Control group (No abdominal binder) - Intervention group (Abdominal binder) **Description:** Postpartum nursing care the follow-up protocol includes the evaluation and record between postpartum 1. and 48. hours of pain level, analgesic administration, follow-up of the puerperal bleeding, and uterine tone, measure of hemodynamic parameters measuring, hemoglobin level and hematocrit ratio, and assessment breastfeeding. **Name:** Postpartum nursing care **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Postpartum pain level evaluation for cesarean section incision in this study is determined using Visual Analog Scale \[VAS\]. VAS is a self-report tool used in the subjective assessment of pain. It is in the form of a 10 cm (100 mm) ruler with no pain at one end (minimum pain score=0) and the most severe pain at the other end (maximum pain score=10). The patients indicate the level of pain they perceive by pointing in accordance with their situation. The numerical data of the pain level of the individual is obtained by measuring the distance from the tip where there is no pain to the specified point with a ruler. The score is increased pain level increases. In the study conducted to ensure the standardization of the VAS, it is reported that the vertical use is better understood by the patients. The VAS has been used in many studies evaluating postoperative cesarean delivery pain. In this study, women's VAS scores were evaluated with a vertical form. **Measure:** Postpartum pain evaluation for cesarean section incision **Time Frame:** Since postpartum arrival to the clinic (postpartum hour 1) up to 48 hours #### Secondary Outcomes **Description:** Postpartum pain level evaluation for abdomen in this study is same the pain assessment postpartum cesarean section incision and is determined using VAS. **Measure:** Postpartum pain evaluation for abdomen **Time Frame:** Since postpartum arrival to the clinic (postpartum hour 1) up to 48 hours **Description:** Puerperal bleeding amount is measured by subtracting the known dry weights (gr) of the pads from those with bleeding, using a sensitive electronic scale. **Measure:** Puerperal bleeding amount measurement **Time Frame:** Since postpartum arrival to the clinic (postpartum hour 1) up to 48 hours **Description:** Postpartum hemoglobin level (g/dl) and hematocrit ratio (%) is obtained from the hospital records in the 6th and 24th hours. **Measure:** Postpartum hemoglobin level and hematocrit ratio **Time Frame:** Up to postpartum 24th hours **Description:** Breastfeeding success is determined by using the Breastfeeding Assesment Scale \[LATCH\]. LATCH is similar to the APGAR scoring system and consists of 5 items: * L; how well the infant latches onto the breast, * A; audible/visible swallowing of the infant, * T; type of nipple, * C; mother's level of comfort regarding the breast and nipple, and * H; position for holding the baby. Each item of the scale is scored as 0, 1 or 2. The score range is 0 to 10. Higher total scores indicate higher success with breastfeeding. **Measure:** Breastfeeding success evaluation **Time Frame:** Since postpartum arrival to the clinic (postpartum hour 1) up to 48 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Can read and write in Turkish, * Conscious and cooperating, * Aged ≥19 to \<35 years, * At the ≥38th gestational week, * Primiparous, * With a healthy, singleton pregnancy and fetus, * Scheduled to undergo cesarean delivery under spinal anesthesia and then undergoes the procedure, * A minimum blood hemoglobin level of ≥11 g/dl and minimum hematocrit ratio of ≥36% at the time of cesarean delivery, * Has the infant with her from cesarean delivery until discharge Exclusion Criteria: * A maternal systemic disease, * A chronic pain problem or regular use of pain medications, * A psychiatric disease, * Scheduled to undergo or has undergone any intervention or drug administration in the pre-/intra-/post-operative period, * Development of any complication in the pre-/intra-/post-operative period, * Drain placement in the postpartum period **Gender Based:** True **Gender Description:** At the ≥38th gestational week **Healthy Volunteers:** True **Maximum Age:** 35 Years **Minimum Age:** 19 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Niğde **Country:** Turkey **Facility:** Nigde Omer Halisdemir University **State:** Central **Zip:** 51200 #### Overall Officials **Official 1:** **Affiliation:** Nigde Omer Halisdemir University **Name:** Pınar Kara, MSc **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Cukurova University **Name:** Evşen Nazik, PhD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Access Criteria:** The published protocol can be used to set an example for scientific research planning. The principal investigator can be contacted to provide data source for meta-analysis and systematic review studies. **Description:** This study will be published as a doctoral thesis. It is also planned to be published as a research article in a scientific journal. **Info Types:** - STUDY_PROTOCOL **IPD Sharing:** YES **Time Frame:** 2 year ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Bleeding - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006470 - Term: Hemorrhage ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Analg - Name: Analgesics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M207501 - Name: Chrysarobin - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02651779 **Acronym:** VIPAR **Brief Title:** Internal Plate Fixation vs. Plaster in Complete Articular Distal Radial Fractures **Official Title:** Internal Plate Fixation vs. Plaster in Complete Articular Distal Radial Fractures #### Organization Study ID Info **ID:** NL51544.018.14 #### Organization **Class:** OTHER **Full Name:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) ### Status Module #### Completion Date **Date:** 2019-02-14 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-03-08 **Type:** ACTUAL **Last Update Submit Date:** 2019-03-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-02-14 **Type:** ACTUAL #### Start Date **Date:** 2015-06-19 **Type:** ACTUAL **Status Verified Date:** 2019-03 #### Study First Post Date **Date:** 2016-01-11 **Type:** ESTIMATED **Study First Submit Date:** 2016-01-04 **Study First Submit QC Date:** 2016-01-08 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Dijklander Ziekenhuis **Class:** OTHER **Name:** Maasstad Hospital **Class:** OTHER **Name:** Maxima Medical Center **Class:** OTHER **Name:** Catharina Ziekenhuis Eindhoven **Class:** OTHER **Name:** Rijnland Hospital **Class:** OTHER **Name:** Diakonessenhuis, Utrecht **Class:** OTHER **Name:** BovenIJ Hospital **Class:** OTHER **Name:** Onze Lieve Vrouwe Gasthuis **Class:** OTHER **Name:** Groene Hart Ziekenhuis **Class:** OTHER **Name:** Reinier de Graaf Groep **Class:** OTHER **Name:** Flevoziekenhuis **Class:** OTHER **Name:** Ziekenhuis Rivierenland **Class:** OTHER **Name:** Radboud University Medical Center **Class:** OTHER **Name:** Ziekenhuis Amstelland **Class:** OTHER **Name:** Medical Center Alkmaar **Class:** OTHER **Name:** Red Cross Hospital Beverwijk **Class:** OTHER **Name:** Zaans Medical Center #### Lead Sponsor **Class:** OTHER **Name:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) #### Responsible Party **Investigator Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) **Investigator Full Name:** J.C. Goslings **Investigator Title:** Prof. dr. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** There is no consensus about the best treatment for patients with displaced complete articular distal radius fractures (AO type C fractures). Despite this lack of consensus and the lack of available literature on comparative data to guide treatment for this patient population, operative treatment with plate fixation has gained popularity. The aim of this study is to compare the functional outcome of open reduction and plate fixation with closed reduction and plaster immobilisation in adult patients (18-75 years) with displaced complete articular distal radius fractures. **Detailed Description:** Distal radius fractures account for 17% of all fractures diagnosed. Two third of those fractures are displaced and need to be reduced. According to the Dutch National Guidelines, displaced distal radius fractures, after adequate reduction confirmed on X-ray, are best treated nonoperatively with cast immobilization. Moreover, the AAOS Clinical Practice Guideline only suggest surgical fixation when the articular step, after reduction, exceeds 2mm. However, both recommendations are based on studies who did not differentiate between intra- and extra-articular distal radius fractures. So, no clear consensus about the best treatment for patients with displaced intra-articular distal radius fractures can be made. Despite this lack of consensus and the lack of available literature on comparative data to guide treatment for this patient population, a rise in use of volar plating has been observed. The goal of open reduction and plate fixation is to restore articular congruity and axial alignment, and to enable early post-operative movement. Several studies show good radiological and functional results using the volar locking plate in unstable displaced distal radius fractures. No studies have been carried out to assess whether operative treatment with plate fixation is superior in displaced complete articular distal radius fractures to nonoperative treatment in patients with these fracture type. Therefore, with this randomized controlled trial the investigators wish to determine the difference in functional outcome, assessed with the Patient Related Wrist Evaluation (PRWE), after open reduction and plate fixation compared to nonoperative treatment with closed reduction and cast immobilization. ### Conditions Module **Conditions:** - Displaced Complete Articular Distal Radius Fractures ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 90 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The control group will be treated with closed reduction and cast immobilization. This will take place under local anaesthesia by means of a haematoma block with 20 cc Lidocaine 1%. Closed reduction will be preferably performed according to the Robert-Jones method. This involves increasing the deformity first, then applying continuous traction and immobilizing wrist and hand in the reduced position. Additional radiographs will be performed to verify the success of the reduction. After this has been confirmed, the wrist will be immobilized initially in a split plaster and later changed into a circular cast for five to six weeks immobilization in total. **Intervention Names:** - Other: Closed reduction and plasterimmobilisation **Label:** Closed reduction and plasterimmobilisation **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** The surgery will be performed by a certified trauma surgeon. According to the current standard treatment protocol, antibiotic prophylaxis will be administered thirty minutes preoperatively. The distal radius will be approached according to Henry, which beholds an incision between the tendon of the flexor carpi radialis muscle and the radial artery. After the fracture site is exposed, the fracture will be reduced and provisionally fixed under fluoroscopy with K-Wires/reduction forceps. An appropriate volar locking plate which best suits the anatomy of the wrist and the fracture type will be selected. Fracture reduction and screw placement will be confirmed by radiographic images. Additionally, fixation can be supported by a dorsal plate or radial column plate. This will be at discretion of the surgeon and depends on the fracture configuration and the position of the fragments. Wound closure will be performed at the discretion of the surgeon using standard techniques. **Intervention Names:** - Procedure: Open reduction and internal plate fixation **Label:** Open reduction and internal plate fixation **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Open reduction and internal plate fixation **Name:** Open reduction and internal plate fixation **Other Names:** - ORIF - Surgical treatment **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Closed reduction and plasterimmobilisation **Name:** Closed reduction and plasterimmobilisation **Other Names:** - Cast - Conservative treatment **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The PRWE is a 15-item questionnaire designed to measure wrist pain and disability in activities of daily living. The PRWE allows patients to rate their levels of wrist pain and disability from 0 to 10, and consists of three subscales: Pain, Function and Cosmetics. **Measure:** Wrist pain and disability measured with the Patient Rated Wrist Evaluation (PRWE) **Time Frame:** 12 months #### Secondary Outcomes **Description:** The Disabilities of the Arm, Shoulder and Hand (DASH) score is a 30-item, self-report questionnaire designed to measure physical function and symptoms in patients with any or several musculoskeletal disorders of the upper limb. **Measure:** Disability of the wrist measured with the Disability of the Arm, Shoulder and Hand (DASH) questionnaire **Time Frame:** 6 weeks and 3, 6 and 12 months **Description:** Quality of Life assessed using the Short Form-36 (SF-36) questionnaire. The SF-36 is a validated multipurpose, short form health survey which contains 36 questions representing eight different health domains. These domains are combined into a mental and physical component scale. From each domain, scores ranging from 0 to 100 points are derived, with lower scores indicating poorer quality of life. **Measure:** Quality of life measured with the SF-36 **Time Frame:** 6 weeks and 3, 6 and 12 months **Description:** Pain as indicated on a visual Analogue Scale (VAS), in which 0 implies no pain and 10 the worst possible pain. Patients will be asked to give an estimation of the type and quantity of pain medication taken during all follow-up visits. **Measure:** Pain measured with the Visual Analogue Scale (VAS) **Time Frame:** 1, 3 and 6 weeks and 3, 6 and 12 months **Description:** Range of motion of the wrist measured on both sides with a handheld goniometer in degrees. ROM includes pronation and supination, ulnar and radial deviation and palmar and dorsal flexion of the wrist. **Measure:** Range of motion measured with a goniometer **Time Frame:** 6 weeks and 3, 6 and 12 months **Description:** Grip strength as measured with a dynamometer in kg as the mean of three measurements. Grip strength will be measured as a percentage of the uninjured side. **Measure:** Grip strength measured with a dynamometer **Time Frame:** 6 weeks and 3, 6 and 12 months **Description:** Radiographs will be performed to ensure that loss of reduction has not occurred. Loss of reduction is defined as \<15° radial inclination, \>15° of dorsal angulation or \>20° of volar angulation, \>3 mm shortening of ulnar variance or \>2 mm of articular step-off or gap. Radial inclination, volar/dorsal tilt, ulnar variance and radial length will be measured digitally in the Picture Archiving and Communication System (PACS) on standard posterior anterior (PA), lateral carporadial and lateral X-rays of the wrist. If loss of reduction occured, operative treatment will be considered, but will be at discretion of the treating surgeon. **Measure:** Number of patients with loss of reduction **Time Frame:** 1, 3 and 6 weeks and 3, 6 and 12 months **Description:** Cost-effectiveness and cost-utility measured with an economic evaluation questionnaire based on the EQ-6D and the Standard Form Health and Labour questionnaire. **Measure:** Cost-effectiveness and cost-utility measured with an economic evaluation questionnaire **Time Frame:** 6 weeks and 3, 6 and 12 months **Description:** Number of complications in both patients treated with plasterimmobilisation and ORIF. Complications include loss of reduction, cross-overs from conservative to operative treatment, fracture malunion or non-union, wound and/or plate infection, tendon irritation and/or rupture, neuropathy and the occurrence of complex regional pain syndrome. **Measure:** Number of complications in both treatment groups **Time Frame:** 1, 3 and 6 weeks and 3, 6 and 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients from 18 - 75 years * AO type C displaced distal radius fracture, as classified on lateral, posterior anterior and lateral carporadial radiographs/CT-scan by a radiologist or trauma surgeon * Acceptable closed reduction obtained immediately after admission to the Emergency Department (\<12hrs) Exclusion Criteria: * Patients with impaired wrist function prior to injury due to arthrosis/neurological disorders of the upper limb * Open distal radius fractures * Multiple trauma patients (Injury Severity Score (ISS) ≥16) * Other fractures of the affected extremity (except from ulnar styloid process) * Fracture of other wrist * Insufficient comprehension of the Dutch language to understand a rehabilitation program and other treatment information as judged by the attending physician * Patient suffering from disorders of bone metabolism other than osteoporosis (i.e. Paget's disease, renal osteodystrophy, osteomalacia) * Patients suffering from connective tissue disease or (joint) hyperflexibility disorders such as Marfan's, Ehler Danlos or other related disorders **Healthy Volunteers:** True **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Amsterdam **Country:** Netherlands **Facility:** Academic Medical Center #### Overall Officials **Official 1:** **Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) **Name:** J. Carel Goslings, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Maasstad Hospital **Name:** Niels W.L. Schep, MD, PhD, MSc **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Mulders MAM, Walenkamp MMJ, Goslings JC, Schep NWL. Internal plate fixation versus plaster in displaced complete articular distal radius fractures, a randomised controlled trial. BMC Musculoskelet Disord. 2016 Feb 9;17:68. doi: 10.1186/s12891-016-0925-y. **PMID:** 26860090 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014947 - Term: Wounds and Injuries - ID: D000005543 - Term: Forearm Injuries - ID: D000001134 - Term: Arm Injuries - ID: D000014954 - Term: Wrist Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M26370 - Name: Fractures, Bone - Relevance: HIGH - As Found: Fracture - ID: M14731 - Name: Radius Fractures - Relevance: HIGH - As Found: Radius Fracture - ID: M2933 - Name: Wrist Fractures - Relevance: HIGH - As Found: Distal Radius Fracture - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M8667 - Name: Forearm Injuries - Relevance: LOW - As Found: Unknown - ID: M4444 - Name: Arm Injuries - Relevance: LOW - As Found: Unknown - ID: M17692 - Name: Wrist Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000050723 - Term: Fractures, Bone - ID: D000011885 - Term: Radius Fractures - ID: D000092503 - Term: Wrist Fractures ### Intervention Browse Module - Browse Branches - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: ChanBlk - Name: Channel Blockers - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M11014 - Name: Lidocaine - Relevance: LOW - As Found: Unknown - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02321579 **Brief Title:** Vitamin B-6 and Glutathione on Inflammation, Homocysteine, Oxidative Stress and Antioxidant Capacities **Official Title:** The Effects of Vitamin B-6 and Glutathione on Inflammatory Responses, Homocysteine Metabolism, Oxidative Stress and Antioxidant Capacities in Patients With Liver Cirrhosis or Hepatocellular Carcinoma #### Organization Study ID Info **ID:** SF14261B #### Organization **Class:** OTHER **Full Name:** Taichung Veterans General Hospital ### Status Module #### Completion Date **Date:** 2017-07 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2014-12-22 **Type:** ESTIMATED **Last Update Submit Date:** 2014-12-19 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2016-12 **Type:** ESTIMATED #### Start Date **Date:** 2014-12 **Status Verified Date:** 2014-12 #### Study First Post Date **Date:** 2014-12-22 **Type:** ESTIMATED **Study First Submit Date:** 2014-12-09 **Study First Submit QC Date:** 2014-12-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Taichung Veterans General Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is designed as a hospital-based cross-sectional and randomized placebo-controlled intervention trial. One hundred and fifty patients with either cirrhosis or cirrhosis combined with hepatocellular carcinoma (HCC) who meet the inclusion criteria will be recruited from Taichung General Veterans Hospital. One hundred patients will be randomly assigned to either the 1) placebo group (n = 25); 2) vitamin B-6 group; (50 mg/d, n = 25); 3) glutathione (GSH) group (500 mg/d, n = 25); or 4) vitamin B-6 (50 mg/d) plus GSH (500 mg/d) group (n = 25) for 3 mo. Data on demography, anthropometry and medical history will be collected. Patients with cirrhosis or cirrhosis combined with HCC will have fasting blood drawn in the clinics. Additionally, patients who participated in the intervention study will have blood drawn at month 0, 1, 2 and 3 during intervention period. Hematological measurements, plasma vitamin B-6 status, GSH, inflammatory markers, homocysteine, cysteine, SAM, SAH, oxidative stress indicator, oxidized GSH and GSH related antioxidant enzyme activities will be analyzed. **Detailed Description:** Liver cirrhosis is now the ninth leading cause of death and hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality among men and women in Taiwan. Vitamin B-6 and glutathione (GSH) are metabolized in liver, the role of vitamin B-6 and GSH playing in the inflammatory responses and antioxidant function would be impaired during hepatic injury. The purpose of this study is going to assess the effects of individual or combined supplementation of vitamin B-6 and GSH on homocysteine, cysteine, the ratio of S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH), oxidative stress, oxidized glutathione (GSSG) and GSH related antioxidant enzyme activities in patients with cirrhosis and cirrhosis combined with HCC. This study is designed as a hospital-based cross-sectional and randomized placebo-controlled intervention trial. One hundred and fifty patients with either cirrhosis or cirrhosis combined with HCC who meet the inclusion criteria will be recruited from Taichung General Veterans Hospital. One hundred patients will be randomly assigned to either the 1) placebo group (n = 25); 2) vitamin B-6 group; (50 mg/d, n = 25); 3) GSH group (500 mg/d, n = 25); or 4) vitamin B-6 (50 mg/d) plus GSH (500 mg/d) group (n = 25) for 3 mo. Data on demography, anthropometry and medical history will be collected. Patients with cirrhosis or cirrhosis combined with HCC will have fasting blood drawn in the clinics. Additionally, patients who participated in the intervention study will have blood drawn at month 0, 1, 2 and 3 during intervention period. Hematological, plasma vitamin B-6 status, GSH, inflammatory markers, homocysteine, cysteine, SAM, SAH, oxidative stress indicator, GSSG and GSH related antioxidant enzyme activities will be measured. Hopefully, the results of this study could provide more pictures on the beneficial effects of vitamin B-6 and GSH supplementation on inflammatory responses, homocysteine, cysteine, the ratio of SAM/SAH, oxidative stress, GSSG and GSH related antioxidant enzyme activities in patients with cirrhosis and HCC. ### Conditions Module **Conditions:** - Liver Cirrhosis - Liver Cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Dextrins **Intervention Names:** - Dietary Supplement: Dextrins **Label:** Negative control **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** 50 mg/d vitamin B-6 **Intervention Names:** - Dietary Supplement: vitamin B-6 **Label:** Supplement 1 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** 500 mg/d Glutathione **Intervention Names:** - Dietary Supplement: Glutathione **Label:** Supplement 2 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** 50 mg/d vitamin B-6 plus 500 mg/d Glutathione **Intervention Names:** - Dietary Supplement: vitamin B-6 - Dietary Supplement: Glutathione **Label:** Supplement 3 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Supplement 1 - Supplement 3 **Description:** 50 mg/d **Name:** vitamin B-6 **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Supplement 2 - Supplement 3 **Description:** 500 mg/d **Name:** Glutathione **Type:** DIETARY_SUPPLEMENT #### Intervention 3 **Arm Group Labels:** - Negative control **Description:** 50 mg/d **Name:** Dextrins **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Measure:** Oxidative stress marker (MDA concentation) **Time Frame:** 3 months #### Secondary Outcomes **Measure:** Glutathione related enzyme activities **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. age between 20 to 80 years old 2. patients are diagnosed as cirrhosis or cirrhosis combined with hepatocellular carcimoma Exclusion Criteria: 1. patients are currently taking any nutrient supplements 2. patients with cardiac, renal, gastrointestinal or diabetic diseases 3. patients are currently taking any medication which will interfere with vitamin B-6 or glutathione metabolism〔i.e., phenobarbital, phenytoin, cycloserine, pyrazinamide, isoniazid, (thio)semicarbazide, hydramitrazine, phenelzine, carbidopa, levodopa, hydralazine, steroids and penicillamine) 4. patients are in pregnant or lactation. **Maximum Age:** 80 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Yi-Chia Huang, PhD **Phone:** +886-4-24730022 **Phone Ext:** 12198 **Role:** CONTACT #### Locations **Location 1:** **City:** Taichung **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Yi-Chia Huang, PhD - **Phone:** +886-4-24730022 - **Phone Ext:** 12198 - **Role:** CONTACT ***Contact 2:*** - **Name:** Shao-Bin Cheng, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Taiwan **Facility:** Taichung Veterans General Hospital **Status:** RECRUITING **Zip:** 40705 #### Overall Officials **Official 1:** **Affiliation:** Taichung Veterans General Hospital **Name:** Shao-Bin Cheng, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M9613 - Name: Carcinoma, Hepatocellular - Relevance: LOW - As Found: Unknown - ID: M11113 - Name: Liver Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11103 - Name: Liver Cirrhosis - Relevance: HIGH - As Found: Liver Cirrhosis - ID: M8485 - Name: Fibrosis - Relevance: HIGH - As Found: Cirrhosis - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008103 - Term: Liver Cirrhosis - ID: D000005355 - Term: Fibrosis ### Intervention Browse Module - Ancestors - ID: D000014815 - Term: Vitamins - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000014803 - Term: Vitamin B Complex ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hemat - Name: Hematinics - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: LOW - As Found: Unknown - ID: M23026 - Name: Vitamin B 6 - Relevance: HIGH - As Found: Health Outcomes - ID: M14583 - Name: Pyridoxal - Relevance: HIGH - As Found: Health Outcomes - ID: M14589 - Name: Pyridoxine - Relevance: HIGH - As Found: Health Outcomes - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: M4292 - Name: Antioxidants - Relevance: LOW - As Found: Unknown - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: T440 - Name: Calciferol - Relevance: LOW - As Found: Unknown - ID: T474 - Name: Vitamin B6 - Relevance: HIGH - As Found: Health Outcomes - ID: T459 - Name: Pyridoxal - Relevance: HIGH - As Found: Health Outcomes - ID: T461 - Name: Pyridoxine - Relevance: HIGH - As Found: Health Outcomes - ID: T446 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: T448 - Name: Folate - Relevance: LOW - As Found: Unknown - ID: T475 - Name: Vitamin B9 - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000025101 - Term: Vitamin B 6 - ID: D000011730 - Term: Pyridoxal - ID: D000011736 - Term: Pyridoxine ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01051479 **Brief Title:** A Pilot C11-Choline PET-CT Imaging Study in Patients With Locally Advanced Esophageal Cancer **Official Title:** A Pilot C11-Choline PET-CT Imaging Study in Patients With Locally Advanced Esophageal Cancer #### Organization Study ID Info **ID:** IRB00012072 #### Organization **Class:** OTHER **Full Name:** Wake Forest University Health Sciences #### Secondary ID Infos **Domain:** Wake Forest University Health Sciences **ID:** CCCWFU 60109 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2013-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-07-02 **Type:** ACTUAL **Last Update Submit Date:** 2018-06-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-08 **Type:** ACTUAL #### Start Date **Date:** 2010-03 **Status Verified Date:** 2018-06 #### Study First Post Date **Date:** 2010-01-18 **Type:** ESTIMATED **Study First Submit Date:** 2010-01-15 **Study First Submit QC Date:** 2010-01-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Wake Forest University Health Sciences #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to evaluate the investigators ability to obtain reliable and meaningful 11C-Choline PET-CT images of esophageal cancer. ### Conditions Module **Conditions:** - Esophageal Cancer **Keywords:** - PET Positron emission tomography - CT X-ray computed tomography - Patients with Locally Advanced Esophageal Cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 22 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: C11-Choline **Label:** C11-Choline **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - C11-Choline **Description:** 15 mCi 11C-choline will be administered intravenously as a bolus. The whole body emission scans will be acquired immediately following the tracer injection. **Name:** C11-Choline **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** To evaluate our ability to obtain reliable and meaningful 11C-Choline PET-CT images of esophageal cancer (pre- and post- chemotherapy). **Time Frame:** 2 years #### Secondary Outcomes **Measure:** Perform semi-quantitative analysis of tracer uptake using standard uptake values (SUV) and qualitative analysis using pure visual analysis. **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Newly diagnosed or recurrent patients with locally advanced esophageal cancer with either squamous or adenocarcinoma histology. * Ability to tolerate PET imaging * Prior malignancy is allowed, but the expectation of survival must be that beyond that expected for patients with locally advanced esophageal cancer. Exclusion Criteria: * Pregnant or lactating females are not eligible for this pilot study. * Patients having received chemotherapy in the 3 months prior to registration for any reason * Patients with metastatic disease requiring chemoradiation for palliation are not allowed. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Winston-Salem **Country:** United States **Facility:** Wake Forest University Health Sciences **State:** North Carolina **Zip:** 27157 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000004935 - Term: Esophageal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M8088 - Name: Esophageal Neoplasms - Relevance: HIGH - As Found: Esophageal Cancer - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M8085 - Name: Esophageal Diseases - Relevance: LOW - As Found: Unknown - ID: T2141 - Name: Esophageal Cancer - Relevance: HIGH - As Found: Esophageal Cancer ### Condition Browse Module - Meshes - ID: D000004938 - Term: Esophageal Neoplasms ### Intervention Browse Module - Ancestors - ID: D000008082 - Term: Lipotropic Agents - ID: D000000960 - Term: Hypolipidemic Agents - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000005765 - Term: Gastrointestinal Agents - ID: D000057847 - Term: Lipid Regulating Agents - ID: D000018697 - Term: Nootropic Agents ### Intervention Browse Module - Browse Branches - Abbrev: NootAg - Name: Nootropic Agents - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: Lipd - Name: Lipid Regulating Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M6034 - Name: Choline - Relevance: HIGH - As Found: Margin - ID: M4278 - Name: Hypolipidemic Agents - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown - ID: M28883 - Name: Lipid Regulating Agents - Relevance: LOW - As Found: Unknown - ID: M20774 - Name: Nootropic Agents - Relevance: LOW - As Found: Unknown - ID: T443 - Name: Choline - Relevance: HIGH - As Found: Margin ### Intervention Browse Module - Meshes - ID: D000002794 - Term: Choline ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02187679 **Brief Title:** Pilot Study for Use of Dysport in Treatment of Vocal Tics in Patients With Tourette's Syndrome **Official Title:** An Open Label, One Arm Pilot Study to Measure the Efficacy and Safety of Dysport in the Treatment of Vocal Tics in Patients With Tourette's Syndrome and Chronic Tic Disorders #### Organization Study ID Info **ID:** DCRC-ISP0016888 #### Organization **Class:** OTHER **Full Name:** Detroit Clinical Research Center ### Status Module #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2015-02-10 **Type:** ESTIMATED **Last Update Submit Date:** 2015-02-09 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2017-06 **Type:** ESTIMATED #### Start Date **Date:** 2014-01 **Status Verified Date:** 2015-02 #### Study First Post Date **Date:** 2014-07-11 **Type:** ESTIMATED **Study First Submit Date:** 2014-07-09 **Study First Submit QC Date:** 2014-07-10 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Ipsen #### Lead Sponsor **Class:** OTHER **Name:** Detroit Clinical Research Center #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** Our intervention will be the injection of Abobotulinum toxin A into the affected site/vocal cords for patients with the diagnosis of Primary Tourette's syndrome. This is an efficacy trial to understand the right dosage of Abobotulinum toxin A which can be affective. The study will involve an injection of 2.5 units of Dysport on each side of the affected vocal cords for patients with a diagnosis of Primary Tourette's syndrome. The patients will also complete a self assessment survey on how vocal tics affect their daily lives. Afterward, a further evaluation of the tics will be conducted by the investigator using the Yale Global Tic Severity Scale. (YGTSS) evaluation. How this will be done is by a licensed ENT (Ear, Nose and Throat) physician. The windpipe will be number by a 2% lidocaine followed by a provoked cough by the patient. This will allow the lidocaine to be sprayed throughout the airway preventing coughing and swallowing during the procedure. An Electromyography (EMG) guidance a needle containing Dysport will be injected into the thyroarytenoid muscles will potentially reduce the vocal dyskinetic features in patients with TS. This needle will be connected to a syringe and once determined active, it will be placed appropriately when the EMG emits a characteristic sound. If this does not occur with the patient then the injection will be administered under direct vision via direct laryngoscopy using an orotracheal injector system. This procedure is conducted in an outpatient clinic because no hospitalization is required. The patient is not allowed to consume food or drink for about 45-60 minutes after the injection. The throat will be numb and may cause coughing and some blood tinged sputum: The expectancy of this outcome is reason to not consider is a serious event. Asprin and ibuprofen is not allowed a week prior to and until the injection at least 3-4 days after to prevent excessive bleeding. The patient is also instructed to ensure that they chew their food thoroughly and drink sufficient water for the initial days after the study intervention. Mild dysphasia may be noted initially which should resolve within a few hours. On Visit 1, the patient will complete all required study documents and forms. Then the ENT physician will proceed with the injection Dysport on the same day. If unforeseen circumstances render the subject unable to be injected on the same day, the intervention must take place within three days and this will be considered V1, follow up events should be scheduled accordingly. **Detailed Description:** The intervention for this pilot study will be the injection of Dysport (Abobotulinum toxin A) into the affected vocal cords for all patients with the diagnosis of Primary Tourette's syndrome. A total of 5 units of Dysport (on each side) will be administered to patients diagnosed with TS to determine whether they exhibit a reduction in the number of vocal tics. The patients will complete a self assessment survey about the manner in which the vocal tics are affecting their daily lives. Further evaluation of the tics will be conducted by the investigator using the Yale Global Tic Severity Scale (YGTSS) evaluation. The intervention will be completed by a licensed ENT (Ears Nose and Throat) physician. The procedure will be conducted in an outpatient clinic setting because no hospitalization is required for this study. The windpipe will be numbed by a 2% lidocaine followed by a provoked cough by the patient. This will enable the lidocaine to be sprayed throughout the airway preventing any coughs or swallowing during the main intervention procedure. Under Electromyography (EMG) guidance a needle containing Dysport will be injected into the thyroarytenoid muscles which will potentially reduce the vocal dyskinetic features in individuals with TS. The needle containing Dysport will be connected to a syringe and once it is determined it is active, it will be placed appropriately when the EMG emits a characteristic sound. A total of 5 units of Dysport (2.5 units on each side) will be administered to the patient. If this does not occur with the patient then the injection will be administered under direct vision via direct laryngoscopy using an orotracheal injector system. The patient will not be allowed to consume food or drink for approximately 45-60 minutes after Dysport has been injected. The throat will be numb after the anesthetic and may cause coughing and some blood tinged sputum which is expected and hence will not be considered a serious event. The patient will not be allowed to consume aspirin or ibuprofen a week prior to and till the intervention for at least 3-4 days after the intervention to prevent excessive bleeding. The patient will also be provided with specific instructions to ensure that they chew their food thoroughly and drink sufficient water for the initial days after the study intervention. Mild dysphasia may be noted initially which should resolve within a few hours. On Visit 1 (Day 1), after the patient has completed all the required study documents and forms, the ENT physician will proceed with the injection of Dysport on the same day. However, if due to unforeseen circumstances, the subject cannot be injected on the same day, the intervention must take place within three days and this will be considered V1 (Day 1) and all follow up visits should be scheduled accordingly. ### Conditions Module **Conditions:** - Tourette Syndrome - Chronic Vocal Tic **Keywords:** - Tourette Syndrome - Tourette's Syndrome - Chronic Vocal Tic - Vocal Tic ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Abobotulinum toxin A Injection **Intervention Names:** - Drug: Abobotulinum toxin A **Label:** Abobotulinum toxin A **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Abobotulinum toxin A **Name:** Abobotulinum toxin A **Other Names:** - Dysport **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Primary Outcome will be the reduction of tics as measured by the physician after 14 days and after 30 days. Only the Yale Global Tic Severity scale will be used to the measure the number of tics and their severity throughout the course of the study. These measurements will be compared with every visit to the score prior to the intervention. **Measure:** Vocal Tic Reduction **Time Frame:** 15 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or Female subjects between the ages of 18 and 65 with a primary clinical diagnosis of TS or chronic Tic Disorder with a duration of tics greater than one year. * Subject is willing and able to provide informed consent. Subjects who are younger than age 21 must have written informed consent provided by the parent or legal guardian and assent provided by the patient when appropriate. * Up to date tetanus immunization. * Yale Global Tic Severity Scale score ≥20 with TS diagnosis or ≥14 for a Chronic Tic disorder. * Female subjects of childbearing age must have a negative urine pregnancy test. Exclusion Criteria: * Patients who have a diagnosis of substance dependence disorder. * Patients diagnosed with a significant and unstable major psychiatric disorder requiring treatment such as: Schizophrenia or Bipolar Disorder. Comorbid conditions such as: Obsessive Compulsive Disorder (OCD) and Attention Deficit Hyperactivity Disorder (ADHD) can be included. * Patients diagnosed with the following types of Obsessive Compulsive Disorders: (All other types of obsessive compulsive disorders are acceptable) * Obsessive Compulsive Disorder for hand washing * Obsessive Compulsive Disorder for finger biting * Obsessive Compulsive Disorder for eye poking * Obsessive Compulsive Disorder for Dermatolomania * Obsessive Compulsive Disorder for Trichotillomania * Obsessive Compulsive Disorder for Head-Banging * Patients with mental retardation. * Patients diagnosed with progressive or degenerative neurological disorders or a structural disorder of the brain from birth, trauma or past infection. * Patients taking more than one agent for the treatment of tics, more than one agent for the treatment of comorbid symptoms or more than one agent for the treatment of ADHD and/or the dose of the current treatment has not been stable for a minimum of 6 weeks. * Female subjects who are pregnant or lactating. * Allergy or hypersensitivity to Dysport or any other BoNT agent or their excipients * Contraindications to treatment with any BoNT-A or BoNT-B preparations * Based on Investigator opinion, patients in whom previous BoNT-A or BoNT-B therapy has failed to produce a clinical response or produced an intolerable adverse event * Anticipated concomitant treatment with BoNT for other than TS * Patients with sexually transmitted diseases such as: HIV, Herpes, Gonorrhea amongst others. * Continuing Medications such as cholinergic medications. * Autoimmune diseases like Myasthenia Gravis * Unable or unwilling to maintain abstinence or use contraception for 28 days following all Dysport injections. * Some forms of Cognitive impairment **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Kimberly Rooker, BS **Phone:** 248-716-7009 **Phone Ext:** 191 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Christopher Clement **Phone:** 248-737-5939 **Role:** CONTACT #### Locations **Location 1:** **City:** Farmington Hills **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Candice Shallal, BS - **Phone:** 248-716-7009 - **Phone Ext:** 190 - **Role:** CONTACT ***Contact 2:*** - **Name:** Edward Dabrowski, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Detroit Clinical Research Center **State:** Michigan **Status:** RECRUITING **Zip:** 48334 #### Overall Officials **Official 1:** **Affiliation:** Detroit Clinical Research Center **Name:** Edward Dabrowski, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000001480 - Term: Basal Ganglia Diseases - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000013981 - Term: Tic Disorders - ID: D000009069 - Term: Movement Disorders - ID: D000020271 - Term: Heredodegenerative Disorders, Nervous System - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000065886 - Term: Neurodevelopmental Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000020820 - Term: Dyskinesias - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M8991 - Name: Tourette Syndrome - Relevance: HIGH - As Found: Tourette Syndrome - ID: M22132 - Name: Tics - Relevance: HIGH - As Found: Vocal Tic - ID: M16739 - Name: Tic Disorders - Relevance: LOW - As Found: Unknown - ID: M25603 - Name: Ganglion Cysts - Relevance: LOW - As Found: Unknown - ID: M16358 - Name: Synovial Cyst - Relevance: LOW - As Found: Unknown - ID: M4774 - Name: Basal Ganglia Diseases - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M12029 - Name: Movement Disorders - Relevance: LOW - As Found: Unknown - ID: M22092 - Name: Heredodegenerative Disorders, Nervous System - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M30644 - Name: Neurodevelopmental Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M22574 - Name: Dyskinesias - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005879 - Term: Tourette Syndrome - ID: D000020323 - Term: Tics - ID: D000013577 - Term: Syndrome ### Intervention Browse Module - Ancestors - ID: D000065087 - Term: Acetylcholine Release Inhibitors - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000018678 - Term: Cholinergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000009465 - Term: Neuromuscular Agents - ID: D000018373 - Term: Peripheral Nervous System Agents ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: VaDiAg - Name: Vasodilator Agents ### Intervention Browse Module - Browse Leaves - ID: M21257 - Name: Botulinum Toxins, Type A - Relevance: HIGH - As Found: Male Adolescents - ID: M250193 - Name: abobotulinumtoxinA - Relevance: HIGH - As Found: Male Adolescents - ID: M5183 - Name: Botulinum Toxins - Relevance: LOW - As Found: Unknown - ID: M3473 - Name: Acetylcholine - Relevance: LOW - As Found: Unknown - ID: M20758 - Name: Cholinergic Agents - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000542869 - Term: abobotulinumtoxinA - ID: D000019274 - Term: Botulinum Toxins, Type A ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05264779 **Brief Title:** The Periviable GOALS Decision Support Tool **Official Title:** Promoting Shared Decision Making in Periviable Care: A Randomized Controlled Trial of the Periviable GOALS Decision Support Tool #### Organization Study ID Info **ID:** R01HS028001 **Link:** https://reporter.nih.gov/quickSearch/R01HS028001 **Type:** AHRQ #### Organization **Class:** OTHER **Full Name:** Indiana University ### Status Module #### Completion Date **Date:** 2026-02 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-22 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-18 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-08 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-06 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2022-03-03 **Type:** ACTUAL **Study First Submit Date:** 2021-12-06 **Study First Submit QC Date:** 2022-03-02 ### Sponsor Collaborators Module #### Collaborators **Class:** FED **Name:** Agency for Healthcare Research and Quality (AHRQ) #### Lead Sponsor **Class:** OTHER **Name:** Indiana University #### Responsible Party **Investigator Affiliation:** Indiana University **Investigator Full Name:** Brownsyne Tucker Edmonds **Investigator Title:** Associate Professor of Obstetrics and Gynecology and Clinical Pediatrics **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The Periviable GOALS (Getting Optimal Alignment around Life Support) decision support tool (DST) is meant to facilitate informed shared decision-making regarding neonatal resuscitation for families facing the threat of a periviable delivery (deliveries occurring between 22 0/7 - 25 6/7 weeks gestational age). It is designed for parents to review independent of their clinician, and is intended to supplement, not replace, clinician counseling. The focus of the DST is the provision of patient-centered outcomes information and assistance with values clarification regarding neonatal outcomes. This is a multisite, randomized controlled trial to test the effect of the Periviable GOALS DST on shared decision making and decision satisfaction. The investigators hypothesize that participants who utilize the GOALS DST will have improved shared decision making and higher decision satisfaction. **Detailed Description:** The investigators will evaluate the Periviable GOALS DST in a randomized controlled trial among 144 pregnant patients between 22 0/7 and 25 6/7 weeks gestation who are hospitalized for a pregnancy complication that threatens periviable delivery. Pregnant patients agreeing to participate will be asked to identify whom they will primarily rely on for assistance in making decisions regarding their delivery plan (e.g., father of the baby, partner, a family member, or any other important individual in the patient's life), referred to as the 'important other' (IO). In terms of IO recruitment goals, the investigators anticipate recruiting 72 IOs. This goal is based on our previous work with a similar population of pregnant patients, in which about half identified an 'important other' to be included in the study. Recruitment will be conducted at Indiana University (IU), the University of California at San Francisco (UCSF), the University of Kansas, the University of California at San Diego (UCSD), Northwestern University, The Ohio State University (OSU), and the University of Pennsylvania (UPenn). This study consists of 3-4 points of data collection, depending on group assignment. Participants will be randomized into a treatment group or control group at the start of the study. All participants will complete the T0 interview, which consists of a set of baseline questionnaires and survey instruments that will be administered in-person, prior to delivery and after they have been counseled on their neonatal treatment options. Immediately following T0, participants who are assigned to the control group will proceed with usual care. Participants who are randomized to the intervention will review the Periviable GOALS DST, which contains outcomes information, values clarification and embedded short documentary style videos. The content focuses largely on helping patients better understand the choice they have between comfort care and life-sustaining efforts in the context of periviable delivery. After viewing the DST, participants will repeat instruments from T0 and provide feedback regarding the tool's acceptability (T1). Another member of the research team will contact all participants to complete follow-up interviews to assess decision quality, neonatal treatment preference and outcome, and mental health. These interviews will be conducted on postpartum day 1 or 2 (T2), at three months postpartum (T3), and at six months postpartum (T4). ### Conditions Module **Conditions:** - Pregnancy Preterm - Premature Birth - Pregnancy Complications - Obstetric Labor, Premature - Obstetric Labor Complications **Keywords:** - Decision making - Periviable delivery - Preterm birth - Risk Communication - Neonatal Resuscitation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomization tables will be generated with SAS v9.4 and will be stratified by recruitment site. The randomization tables will be uploaded into REDCap's randomization module by the data manager. RAs will not be allowed access to these randomization tables to ensure that the data collection remains unbiased. ##### Masking Info **Masking:** DOUBLE **Masking Description:** The assessors of the primary outcome will be blinded to the participant's treatment group. The investigators will utilize a two-research assistant (RA) recruitment approach, wherein one RA collects the T0/T1 information and randomizes the patient to a study arm; and a second RA collects the T2-T4 data, remaining a blinded assessor of the primary outcomes of interest. Further, all other research personnel, including the data manager, statistician, and study investigators will be blinded to the participant's treatment group to minimize the potential for bias in the analysis. **Who Masked:** - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 216 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants assigned to this group will proceed with usual medical care and treatment, consisting of counseling by the teams of obstetricians and/or neonatologists at the respective study sites. **Label:** Usual Care (control) **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Participants randomized to the intervention will be presented with the Periviable GOALS DST and instructed to review the DST in its entirety. The participant will complete the education and values clarification components of the DST with the Recruitment RA present to confirm completion. Following completion of the GOALS DST, the Recruitment RA will repeat knowledge and decisional conflict instruments and assess acceptability. **Intervention Names:** - Other: Periviable GOALS DST **Label:** Periviable GOALS DST Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Periviable GOALS DST Group **Description:** An iPad application that contains outcomes information, values clarification and embedded short documentary style videos. The tool was designed with low-literacy and low-numeracy populations in mind, and utilizes graphics and video content to enhance meaning-making of complex medical information and jargon. The GOALS DST refers patients back to their physicians to discuss specific treatment options, local outcomes, and management strategies available to them. The DST's content focuses largely on helping patients better understand the choice they have between comfort care and life-sustaining efforts in the context of periviable delivery. **Name:** Periviable GOALS DST **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** 9-item Shared Decision Making Questionnaire (SDM-Q-9) administered in-person or via phone/Zoom call. Scores range from 0 to 100, with a higher score correlating to higher shared decision making. **Measure:** Shared Decision Making **Time Frame:** 1 day to 2 weeks after delivery **Description:** 6-item Satisfaction with Decision Scale, administered in-person or via phone/Zoom call at three time points. There are 5 response categories ranging from 1 (strongly disagree) to 5 (strongly agree) with higher scores correlating to higher decision satisfaction. **Measure:** Decision Satisfaction **Time Frame:** 1 day to 2 weeks after delivery #### Secondary Outcomes **Description:** 16-item Decisional Conflict Scale (DCS) administered during Zoom interview. There are 5 response categories, ranging from 0 (no decisional conflict) to 100 (extremely high decisional conflict). **Measure:** Decisional Conflict **Time Frame:** 1 day to 2 weeks after delivery, 3 months after delivery, and 6 months after delivery **Description:** 21-item knowledge scale, administered in-person prior to delivery. Scores range from 0-21 with higher scores indicating greater knowledge. **Measure:** Knowledge about Periviable Delivery **Time Frame:** Before delivery **Description:** 5-item Decision Regret Scale, administered in person or via phone/Zoom call at three time points. There are 5 response categories ranging from 1 (strongly agree) to 5 (strongly disagree) with higher scores correlating to higher decision regret. **Measure:** Decision Regret **Time Frame:** 1 day to 2 weeks after delivery, 3 months after delivery, and 6 months after delivery **Description:** 5-item subscale from the Decision Evaluation Scale, administered in-person or via phone/Zoom call at three time points. There are five responses ranging from 1 (strongly disagree) to 5 (strongly agree) with higher scores correlating to lower decision control. **Measure:** Decision Control **Time Frame:** 1 day to 2 weeks after delivery, 3 months after delivery, and 6 months after delivery **Description:** 9-item Patient Health Questionnaire (PHQ-9), administered in-person and via phone/Zoom calls at four time points. Participants are asked to indicate how much they have been bothered by a list of problems over the last two weeks. There are 4 response ranging from 0 (not at all) to 4 (nearly every day). Total scores range from 0-27 and are organized into 5 categories: minimal depression (0-4), mild depression (5-9), moderate depression (10-14), moderately severe depression (15-19), and severe depression (20-27). **Measure:** Depression **Time Frame:** Before delivery, up to 2 weeks postpartum, 3 months postpartum, and 6 months postpartum. **Description:** 7-item Generalized Anxiety Disorder (GAD-7), administered in-person and via phone/Zoom calls at four time points. Participants are asked to indicate how much they have been bothered by a list of problems over the last two weeks. There are 4 responses ranging from 0 (not at all) to 4 (nearly every day). Total scores range from 0-21 and are organized into 4 categories: minimal anxiety (0-4), mild anxiety (5-9), moderate anxiety (10-14), and severe anxiety (15-21). **Measure:** Anxiety **Time Frame:** Before delivery, up to 2 weeks postpartum, 3 months postpartum, and 6 months postpartum. **Description:** 22-item Impact of Events Scale-Revised (IES-R), administered in-person or via phone/Zoom call. Participants are asked to indicate how much they were distressed or bothered during the past seven days by each difficulty listed, in relation to losing their child to periviable delivery or their delivery experience (if their child survived). There are 5 response categories ranging from 0 (not at all) to 4 (extremely) with total scores ranging from 0-88. Scores of 33 or higher indicates a probable diagnoses for PTSD. **Measure:** Post-Traumatic Stress Disorder **Time Frame:** Before delivery, up to 2 weeks postpartum, 3 months postpartum, and 6 months postpartum. **Description:** Medical records will be reviewed for documentation of parental treatment preference (attempt resuscitation vs. palliation), treatment provided, and neonatal outcome (death, neurodevelopmental impairment, gestational age at delivery). The investigators will also assess treatment preferences at the first interview to account for baseline difference. To do so, participants will be asked whether they have been asked to make any treatment decisions regarding their baby, and if so, the types of decisions they were asked to make. If the participant identifies resuscitation versus palliative care as a decision they have been asked to make, they will be asked about their preference regarding these two options. If they make no mention of resuscitation the investigators will ask if the doctors have discussed resuscitation (Y/N), comfort care (Y/N), and then ask if they have decided which treatment option they prefer (Resuscitation, Comfort Care, Undecided). **Measure:** Number of Parents who Preferred Resuscitation vs. Palliation **Time Frame:** Before delivery and 1-2 days after delivery **Description:** Medical records will be reviewed for documentation of neonatal treatment provided (resuscitation vs. palliation). **Measure:** Neonatal Treatment Provided **Time Frame:** Up to 6 months after delivery **Description:** Medical records will be reviewed for documentation of neonatal outcome (death, neurodevelopmental impairment, gestational age at delivery). **Measure:** Neonatal Outcome **Time Frame:** Up to 6 months after delivery **Description:** Decision Aid Acceptability Questionnaire that elicits feedback from viewers of the GOALS DST including acceptability of format, whether the information was presented in a balanced/fair manner, clarity of information, helpfulness of the DST, and whether users would recommend it to other parents. Will be administered in-person, immediately following viewing the Periviable GOALS DST. **Measure:** Acceptability of the decision support tool **Time Frame:** Before delivery **Description:** 10-item Preparation for Decision Making Scale (PrepDM) that covers all of the core attributes for assessing the quality of the decision-making process except the extent to which patients feel informed about options and outcomes. Will be administered in-person, immediately following viewing the Periviable GOALS DST. There are 5 response categories ranging from 1 (not at all) to 5 (a great deal) with higher scores indicating higher perceived level of preparation for decision making. **Measure:** Preparation for Decision Making **Time Frame:** Before delivery **Description:** 6-item Satisfaction with Decision Scale, administered in-person or via phone/Zoom call at three time points. There are 5 response categories ranging from 1 (strongly disagree) to 5 (strongly agree) with higher scores correlating to higher decision satisfaction. **Measure:** Decision Satisfaction **Time Frame:** 3 months and 6 months after delivery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria for Pregnant Persons: * Adults (18 years or older) * Pregnant between 22 0/7 to 25 6/7 weeks gestation (this window may be slightly different for each recruitment site, as the gestational window that defines periviable delivery varies by institution). * Presenting to Labor \& Delivery at an approved study site with a pregnancy complication that poses the potential threat of or need for periviable delivery (e.g., rupture of membranes, preterm labor, shortened cervix, pre-eclampsia, and growth restriction). * Must have been counseled on their neonatal treatment options (e.g. resuscitation, comfort care) by their healthcare team prior to being approached by the study team. Inclusion Criteria for Important Others: * Adults (18 years or older) * 1 per pregnant person * Is identified by the pregnant person as someone who will be involved in making decisions for the baby * Must be present at the time of randomization to participate Exclusion Criteria: * Under 18 years of age * Incarcerated * Medically unstable (i.e. in active labor and dilated 6cm or more) * Emotionally unstable * Have not been counseled by their healthcare team regarding neonatal treatment options * Are not admitted to Labor \& Delivery for reasons indicative of a threatened early delivery * If they are experiencing a known fatal fetal anomaly * Are not present at the time of randomization (only for important others) **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Shelley Hoffman, MPH **Phone:** 3172789636 **Role:** CONTACT #### Locations **Location 1:** **City:** San Diego **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Samantha LaBelle - **Role:** CONTACT ***Contact 2:*** - **Name:** Cynthia Gyamfi-Bannerma, MD, MS - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** The University of California San Diego **State:** California **Status:** RECRUITING **Zip:** 92121 **Location 2:** **City:** San Francisco **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Kimberly Coleman-Phox, MPH - **Phone:** 415-476-6406 - **Role:** CONTACT **Country:** United States **Facility:** University of California San Francisco **State:** California **Status:** RECRUITING **Zip:** 94143 **Location 3:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Brittney M Williams, MPH - **Phone:** 312-503-3476 - **Role:** CONTACT ***Contact 2:*** - **Name:** Lynn M Yee, MD, MPH - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Northwestern University **State:** Illinois **Status:** RECRUITING **Zip:** 60611 **Location 4:** **City:** Indianapolis **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Shelley M Hoffman, MPH - **Phone:** 317-278-9636 - **Role:** CONTACT **Country:** United States **Facility:** Indiana University **State:** Indiana **Status:** RECRUITING **Zip:** 46202 **Location 5:** **City:** Kansas City **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Raysa Williams - **Phone:** 913-588-5000 - **Role:** CONTACT ***Contact 2:*** - **Name:** Megan M Thomas, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** The University of Kansas Medical Center **State:** Kansas **Status:** RECRUITING **Zip:** 66160 **Location 6:** **City:** Columbus **Contacts:** ***Contact 1:*** - **Email:** mailto:[email protected] - **Name:** Anna Bartholomew, MPH, RN - **Phone:** 614-685-3229 - **Role:** CONTACT ***Contact 2:*** - **Name:** William Grobman, MD, MBA - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** The Ohio State University **State:** Ohio **Status:** RECRUITING **Zip:** 43210 **Location 7:** **City:** Philadelphia **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Meaghan McCabe, MPH - **Phone:** 973-747-2824 - **Role:** CONTACT ***Contact 2:*** - **Name:** Sindhu K Srinivas, MD, MSCE - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** University of Pennsylvania **State:** Pennsylvania **Status:** NOT_YET_RECRUITING **Zip:** 19104 #### Overall Officials **Official 1:** **Affiliation:** Indiana University School of Medicine **Name:** Brownsyne Tucker Edmonds, MD, MPH, MS **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of California, San Francisco **Name:** Miriam Kuppermann, PhD, MPH **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Participant data will only be shared with approved members of the study team. **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14127 - Name: Pregnancy Complications - Relevance: HIGH - As Found: Pregnancy Complications - ID: M25869 - Name: Premature Birth - Relevance: HIGH - As Found: Premature - ID: M10764 - Name: Obstetric Labor Complications - Relevance: HIGH - As Found: Obstetric Labor Complications - ID: M10772 - Name: Obstetric Labor, Premature - Relevance: HIGH - As Found: Obstetric Labor, Premature - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000047928 - Term: Premature Birth - ID: D000011248 - Term: Pregnancy Complications - ID: D000007744 - Term: Obstetric Labor Complications - ID: D000007752 - Term: Obstetric Labor, Premature ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03696979 **Brief Title:** The Effect of Myofascial Induction and Therapeutic Pain Education in Chronic Low Back Pain **Official Title:** The Effect of Myofascial Induction and Therapeutic Pain Education in Chronic Low Back Pain #### Organization Study ID Info **ID:** 76678999 #### Organization **Class:** OTHER **Full Name:** Medipol University ### Status Module #### Completion Date **Date:** 2020-02-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-02-20 **Type:** ACTUAL **Last Update Submit Date:** 2020-02-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-09-20 **Type:** ACTUAL #### Start Date **Date:** 2018-11-20 **Type:** ACTUAL **Status Verified Date:** 2020-02 #### Study First Post Date **Date:** 2018-10-05 **Type:** ACTUAL **Study First Submit Date:** 2018-09-21 **Study First Submit QC Date:** 2018-10-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Medipol University #### Responsible Party **Investigator Affiliation:** Medipol University **Investigator Full Name:** Mehmet ÜNAL **Investigator Title:** director physiotherapist **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this study was to investigate the effects of therapeutic pain education and myofascial induction therapy on pain and function in patients with chronic low back pain. In the literature, studies on myofascial induction therapy in patients with chronic low back pain are very limited and there is no study comparing therapeutic pain training. **Detailed Description:** Lumbar pain has become a major health problem which is growing and is very common in all societies and negatively affects the full well-being of the individual. It has been reported that 80% of the population experienced low back pain at any time in their lives. The prolongation of this painful process affects the physical, mental and psychological state of the patient and limits its daily functions. The acute or chronic pain determines the nature and duration of pain. Low back pain lasting 12 weeks or more is defined as chronic. In chronic diseases, lumbar pain, which is the first one, restricts the daily activities of the person due to current chronic pain or deterioration of functional status and causes loss of labor force. Myofascial induction therapy is a therapy concept focused on optimizing function and balance within the fascial system. The approach aims at global recovery, local correction and painless body use. Superficial procedures are directed to surface and / or local restrictions that can be directly detected by palpation. Deep myofascial induction therapy is a method that eliminates the limitations of the myofascial system and the three-dimensional pressures. Therapeutic pain education is a training intervention that aims to reduce pain and disability by helping patients better understand the biological processes that support pain states. The neurobiology of pain and pain processed by the nervous system is explained to the patient in detail. Changes the patient's olab viewpoint to pain. For example, the patient believes that the cause of pain is caused by tissue damage. The patient who receives pain education understands that the cause of pain is the hypersensitive central nervous system. As a result, the patient's fear avoidance behavior decreases and he starts to move more easily. Because the sensitivity of the central nervous system will be alleviated, the perceived pain will decrease. ### Conditions Module **Conditions:** - Back Pain ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Twice a week for 8 weeks. Lumbar interfacial field stroke application, Lumbar interfacial field to deep application, Lumbar region cross-hands induction technique, Hip flexor region induction. **Intervention Names:** - Other: Myofascial induction therapy **Label:** myofascial induction **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Pain education,twice a week for 8 weeks. The mechanism of pain,Pain processing in the center, How sensitive the central nervous system is in chronic pain, Pain becomes chronic with the contribution of factors, Problems related to fear of pain will be explained in detail. **Intervention Names:** - Other: Therapeutic pain education **Label:** Therapeutic Pain education **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - myofascial induction **Description:** Myofascial induction therapy is a therapy concept focused on optimizing function and balance within the fascial system. The approach aims at global recovery, local correction and painless body use. **Name:** Myofascial induction therapy **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Therapeutic Pain education **Description:** Therapeutic pain education is a training intervention that aims to reduce pain and disability by helping patients better understand the biological processes that support pain states. The neurobiology of pain and pain processed by the nervous system is explained to the patient in detail. Changes the patient's olab viewpoint to pain. For example, the patient believes that the cause of pain is caused by tissue damage. The patient who receives pain training understands that the cause of pain is the hypersensitive central nervous system. As a result, the patient's fear avoidance behavior decreases and he starts to move more easily. Because the sensitivity of the central nervous system will be alleviated, the perceived pain will decrease. **Name:** Therapeutic pain education **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The McGill Pain Questionnaire (MPQ) is a self-reporting measure of pain used for patients with a number of diagnoses. It assesses both quality and intensity of subjective pain. Seven words are selected from the following categories: dimension 1 to 10 (pain descriptors), three words; dimensions 11 to 15 (affective components of pain), dimension 16 (evaluation of pain) one word, and dimension 17 to 20 (miscellaneous) one word. Scores are tabulated by summing values associated with each word; scores range from 0 (no pain) to 78 (severe pain). Qualitative differences in pain may be reflected in respondent's word choice **Measure:** Mc Gill pain survey **Time Frame:** 8 week **Description:** Roland-Morris Disability Questionnaire\[1\] is designed to assess self-rated physical disability caused by low back pain. There are different questionnaires available, which differ from each other in the number of statements: 24-, 18- and 11-item questionnaire. The patient is asked to tick a statement when it applies to him that specific day, this makes it possible to follow changes in time. The end score is the sum of the ticked boxes. The score ranges from 0 (no disability) to 11, 18 or 24 (max. disability) depending on the questionnaire that is used. **Measure:** Roland Morris Disability index **Time Frame:** 8 week **Description:** The Fear-Avoidance Beliefs Questionnaire (FABQ) is a patient reported questionnaire which specifically focuses on how a patient's fear avoidance beliefs about physical activity and work may affect and contribute to their low back pain and resulting disability. The questionnaire consists of 16 items in which a patient rates their agreement with each statement on a 7-point Likert scale. Where 0= completely disagree, 6=completely agree. There is a maximum score of 96. **Measure:** Survey of fear avoidance beliefs **Time Frame:** 8 week **Description:** fingertip-to-floor (FTF) test as an outcome measure on the great majority of my patients presenting with lumbo-pelvic pain, for the simple reason that forward bending is one of the more painful and limited movements, especially in those with neural symptoms. The FTF test has been shown to have excellent reliability without the use of standardized instructions and patient positioning. It must be stated that the FTF test has been criticized for not measuring isolated lumbar flexion range of motion, with the argument that forward bending range is also based on pelvic, hip, thoracic spine, dural and shoulder mobility. **Measure:** Evaluation of mobility (finger ground test) **Time Frame:** 8 week **Description:** The Short Form (36) Health Survey is a multi-purpose survey designed to capture adult patients' perceptions of their own health and well-being. Based on a much longer survey developed in the 1980's by Ware, J.E., the SF-36 has 36 items grouped in 8 dimensions: physical functoning, physicial and emotional limitations, social functioning, bodily pain, general and mental health. **Measure:** SF.36 Healthy life survey **Time Frame:** 8 week **Description:** thoracolumbar fascia Measurements and evaluation of TLF were obtained using single blind method when investigator didn't know any clinical information about a patient. Thickness of TLF was measured from both sides of a spine in the direction perpendicular to the skin. According to methodic of Langevin mentioned above TLF was divided to subdermal (SD) and supramuscular (SM). The general thickness of TLF is defined as the distance between deep border of the dermis and the superficial border of the muscle. TLF is hyperechogenic one or several layers (planes) structure which thickness is measured as a distance between the muscle and subdermal part of fascia. **Measure:** Ultrasound examination of thoracolumbar fascia **Time Frame:** 8 week ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Between 25-65 years old * Low back pain for at least 12 weeks * Physical therapy in the last 1 month * There is no other disease that may cause low back pain. Exclusion Criteria: * Stem pressure associated with pain * Having severe discopathy * Available compression fracture * To have rheumatic or inflammatory disease that may cause back pain. **Maximum Age:** 65 Years **Minimum Age:** 25 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Kocaeli **Country:** Turkey **Facility:** Mehmet Unal **State:** Select... **Zip:** 41100 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M4714 - Name: Back Pain - Relevance: HIGH - As Found: Back Pain - ID: M19433 - Name: Low Back Pain - Relevance: HIGH - As Found: Low Back Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001416 - Term: Back Pain - ID: D000017116 - Term: Low Back Pain ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04401579 **Brief Title:** Adaptive COVID-19 Treatment Trial 2 (ACTT-2) **Official Title:** A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-2) #### Organization Study ID Info **ID:** 20-0006 ACTT-2 #### Organization **Class:** NIH **Full Name:** National Institute of Allergy and Infectious Diseases (NIAID) ### Status Module #### Completion Date **Date:** 2020-07-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-03-14 **Type:** ACTUAL **Last Update Submit Date:** 2022-03-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-07-31 **Type:** ACTUAL #### Results First Post Date **Date:** 2021-04-26 **Type:** ACTUAL **Results First Submit Date:** 2021-02-25 **Results First Submit QC Date:** 2021-04-22 #### Start Date **Date:** 2020-05-08 **Type:** ACTUAL **Status Verified Date:** 2020-04 #### Study First Post Date **Date:** 2020-05-26 **Type:** ACTUAL **Study First Submit Date:** 2020-05-22 **Study First Submit QC Date:** 2020-05-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NIH **Name:** National Institute of Allergy and Infectious Diseases (NIAID) #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False ### Description Module **Brief Summary:** ACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29. **Detailed Description:** This study is an adaptive randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. New arms can be introduced according to scientific and public health needs. There will be interim monitoring to allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. This adaptive platform is used to rapidly evaluate different therapeutics in a population of those hospitalized with moderate to severe COVID-19. The platform will provide a common framework sharing a similar population, design, endpoints, and safety oversight. New stages with new therapeutics can be introduced. One independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data in all stages to make recommendations about early study closure or changes to study arms. ACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized). OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and 29 (if the subject attends an in-person visit or are still hospitalized). The primary outcome is time to recovery by Day 29. A key secondary outcome evaluates treatment-related improvements in the 8-point ordinal scale at Day 15. Each stage may prioritize different secondary endpoints for the purpose of multiple comparison analyses. Contacts: 20-0006 Central Contact Telephone: 1 (301) 7617948 Email: [email protected] ### Conditions Module **Conditions:** - COVID-19 **Keywords:** - Adaptive - COVID-19 - Efficacy - Multicenter - novel coronavirus - Safety ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1033 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **Intervention Names:** - Drug: Remdesivir - Drug: Baricitinib **Label:** Remdesivir plus Baricitinib **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **Intervention Names:** - Other: Placebo - Drug: Remdesivir **Label:** Remdesivir plus Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Remdesivir plus Placebo **Description:** The matching Baricitinib placebo contains lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. The coating for the placebo tablet is identical to that of the corresponding active tablet. **Name:** Placebo **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Remdesivir plus Baricitinib - Remdesivir plus Placebo **Description:** Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide. **Name:** Remdesivir **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Remdesivir plus Baricitinib **Description:** Baricitinib is a Janus kinase (JAK) inhibitor with the chemical name \[1-(ethylsulfonyl)-3-(4-(7Hpyrrolo(2,3-d)pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl\]acetonitrile Each tablet contains 2 mg of baricitinib and the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, ferric oxide, lecithin (soya), polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide. **Name:** Baricitinib **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. **Measure:** Time to Recovery **Time Frame:** Day 1 through Day 29 **Description:** Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. **Measure:** Time to Recovery by Race **Time Frame:** Day 1 through Day 29 **Description:** Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. **Measure:** Time to Recovery by Ethnicity **Time Frame:** Day 1 through Day 29 **Description:** Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. **Measure:** Time to Recovery by Sex **Time Frame:** Day 1 through Day 29 #### Secondary Outcomes **Description:** Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Alanine Transaminase (ALT) **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Aspartate Transaminase (AST) **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Creatinine **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Glucose **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Hemoglobin **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Platelets **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate INR was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Prothrombin International Normalized Ratio (INR) **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Total Bilirubin **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in White Blood Cell Count (WBC) **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** BBlood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Neutrophils **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Lymphocytes **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Monocytes **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Basophils **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in Eosinophils **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. **Measure:** Change in National Early Warning Score (NEWS) From Baseline **Time Frame:** Days 1, 3, 5, 8, 11, 15, 22, and 29 **Description:** Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. **Measure:** Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) **Time Frame:** Day 1 through Day 29 **Description:** An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. **Measure:** Percentage of Participants Reporting Serious Adverse Events (SAEs) **Time Frame:** Day 1 through Day 29 **Description:** Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. **Measure:** Duration of Hospitalization **Time Frame:** Day 1 through Day 29 **Description:** Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die **Measure:** Duration of New Non-invasive Ventilation or High Flow Oxygen Use **Time Frame:** Day 1 through Day 29 **Description:** Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die **Measure:** Duration of New Oxygen Use **Time Frame:** Day 1 through Day 29 **Description:** Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die **Measure:** Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use **Time Frame:** Day 1 through Day 29 **Description:** Duration of oxygen use was measured in days among participants who were on oxygen in based, calculated in two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. **Measure:** Duration of Oxygen Use **Time Frame:** Day 1 through Day 29 **Description:** Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses of Remdesivir, or in the 14 doses of Baricitinib/placebo. **Measure:** Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics **Time Frame:** Day 1 through Day 14 **Description:** The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline **Measure:** Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use **Time Frame:** Day 1 through Day 29 **Description:** The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline **Measure:** Percentage of Participants Requiring New Oxygen Use **Time Frame:** Day 1 through Day 29 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement. **Measure:** Mean Change in the Ordinal Scale **Time Frame:** Day 1, 3, 5, 8, 11, 15, 22, and 29 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Data was imputed using last observation carried forward or worst possible score based on hospitalization status (2 if not hospitalized, 7 if hospitalized) when there was a change in hospitalization status since last score. Deaths were imputed as an 8. **Measure:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 **Time Frame:** Day 15 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Measure:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 **Time Frame:** Day 1 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Measure:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 **Time Frame:** Day 3 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Measure:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 **Time Frame:** Day 5 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Measure:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 **Time Frame:** Day 8 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Measure:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 **Time Frame:** Day 11 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Measure:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 **Time Frame:** Day 22 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Measure:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 **Time Frame:** Day 29 **Description:** The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates. **Measure:** 14-day Participant Mortality **Time Frame:** Day 1 through Day 15 **Description:** The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates. **Measure:** 28-day Participant Mortality **Time Frame:** Day 1 through Day 29 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant **Measure:** Time to an Improvement of One Category Using an Ordinal Scale **Time Frame:** Day 1 through Day 29 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant **Measure:** Time to an Improvement of Two Categories Using an Ordinal Scale **Time Frame:** Day 1 through Day 29 **Description:** The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant. **Measure:** Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First **Time Frame:** Day 1 through Day 29 **Description:** Blood to evaluate CRP was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in C-reactive Protein (CRP) **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Description:** Blood to evaluate d-dimer concentration was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Measure:** Change From Baseline in D-dimer Concentration **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Admitted to a hospital with symptoms suggestive of COVID-19. 2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures. 3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures. 4. Male or non-pregnant female adult \> / = 18 years of age at time of enrollment. 5. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen, as documented by either of the following: * PCR positive in sample collected \< 72 hours prior to randomization; OR * PCR positive in sample collected \>/= 72 hours prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking \>24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection. 6. Illness of any duration, and at least one of the following: * Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR * SpO2 \< / = 94% on room air, OR * Requiring supplemental oxygen, OR * Requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO). 7. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29. 8. Agrees to not participate in another clinical trial for the treatment of COVID-19 through Day 29. Exclusion Criteria: 1. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) \> 5 times the upper limit of normal. 2. Estimated glomerular filtration rate (eGFR) \< 30 ml/min or patient is receiving hemodialysis or hemofiltration at time of screening. 3. Neutropenia (absolute neutrophil count \<1000 cells/microliter) (\<1.0 x 103/microliter or \<1.0 GI/L). 4. Lymphopenia (absolute lymphocyte count \<200 cells/microliter) (\<0.20 x 103/microliter or \<0.20 GI/L) 5. Pregnancy or breast feeding. 6. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours. 7. Allergy to any study medication. 8. Received three or more doses of remdesivir, including the loading dose, outside of the study under the EUA (or similar mechanism) for COVID-19. 9. Received convalescent plasma or intravenous immunoglobulin \[IVIg\]) for COVID-19, the current illness for which they are being enrolled. 10. Received small molecule tyrosine kinase inhibitors (e.g. baricitinib, imatibib, genfinitib), in the 1 week prior to screening 11. Received monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 \[IL-1\], anti-IL-6 \[tocilizumab or sarilumab\]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening. 12. Received monoclonal antibodies targeting B-cell (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening. 13. Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with baricitinib is larger than the risk of COVID-19. 14. Received \>/= 20 mg/day of prednisone or equivalent for \>/=14 consecutive days in the 4 weeks prior to screening. 15. Use of probenecid that cannot be discontinued at study enrollment. 16. Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required). 17. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product. 18. Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects. 19. Have a history of VTE (deep vein thrombosis \[DVT\] or pulmonary embolism \[PE\]) within 12 weeks prior to screening or have a history of recurrent (\>1) VTE (DVT/PE). 20. Immunocompromised patients, patients with a chronic medical condition, or those taking a medication that cannot be discontinued at enrollment, who, in the judgment of PI, are at increased risk for serious infections or other safety concerns given the study products. **Maximum Age:** 99 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** University of Alabama at Birmingham School of Medicine - Infectious Disease **State:** Alabama **Zip:** 35233 **Location 2:** **City:** La Jolla **Country:** United States **Facility:** University of California San Diego Health - Jacobs Medical Center **State:** California **Zip:** 29037 **Location 3:** **City:** Los Angeles **Country:** United States **Facility:** University of California Los Angeles Medical Center - Westwood Clinic **State:** California **Zip:** 90095 **Location 4:** **City:** Orange **Country:** United States **Facility:** University of California Irvine Medical Center - Infectious Disease **State:** California **Zip:** 92868-3298 **Location 5:** **City:** Palo Alto **Country:** United States **Facility:** VA Palo Alto Health Care System - Infectious Diseases **State:** California **Zip:** 94304-1207 **Location 6:** **City:** Palo Alto **Country:** United States **Facility:** Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases **State:** California **Zip:** 94304-1503 **Location 7:** **City:** Sacramento **Country:** United States **Facility:** University of California Davis Medical Center - Internal Medicine - Infectious Disease **State:** California **Zip:** 95817-1460 **Location 8:** **City:** San Diego **Country:** United States **Facility:** Naval Medical Center San Diego - Infectious Disease Clinic **State:** California **Zip:** 92314 **Location 9:** **City:** San Francisco **Country:** United States **Facility:** University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine **State:** California **Zip:** 94110-2859 **Location 10:** **City:** West Hollywood **Country:** United States **Facility:** Cedars Sinai Medical Center **State:** California **Zip:** 90048-1804 **Location 11:** **City:** Aurora **Country:** United States **Facility:** Eastern Colorado Health Care System **State:** Colorado **Zip:** 80045 **Location 12:** **City:** Denver **Country:** United States **Facility:** Denver Health Division of Hospital Medicine - Main Campus **State:** Colorado **Zip:** 80204 **Location 13:** **City:** Washington **Country:** United States **Facility:** Georgetown University Medical Center - Division of Infectious Diseases **State:** District of Columbia **Zip:** 20007 **Location 14:** **City:** Gainesville **Country:** United States **Facility:** University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine **State:** Florida **Zip:** 32610 **Location 15:** **City:** Miami **Country:** United States **Facility:** University of Miami Miller School of Medicine - Infectious Diseases **State:** Florida **Zip:** 33136 **Location 16:** **City:** Decatur **Country:** United States **Facility:** Emory Vaccine Center - The Hope Clinic **State:** Georgia **Zip:** 30030-1705 **Location 17:** **City:** Decatur **Country:** United States **Facility:** Atlanta VA Medical Center - Infectious Diseases Clinic **State:** Georgia **Zip:** 30033 **Location 18:** **City:** Chicago **Country:** United States **Facility:** Northwestern Hospital - Infectious Disease **State:** Illinois **Zip:** 60611-2908 **Location 19:** **City:** Chicago **Country:** United States **Facility:** University of Illinois at Chicago College of Medicine - Division of Infectious Diseases **State:** Illinois **Zip:** 60612 **Location 20:** **City:** Indianapolis **Country:** United States **Facility:** Indiana University School of Medicine - Infectious Diseases **State:** Indiana **Zip:** 46202 **Location 21:** **City:** Kenner **Country:** United States **Facility:** Ochsner Medical Center - Kenner - Department of Infectious Diseases **State:** Louisiana **Zip:** 70065 **Location 22:** **City:** New Orleans **Country:** United States **Facility:** Southeast Louisiana Veterans Health Care System (SLVHCS) - Section of Infectious Diseases **State:** Louisiana **Zip:** 70119 **Location 23:** **City:** Baltimore **Country:** United States **Facility:** University of Maryland School of Medicine - Center for Vaccine Development - Baltimore **State:** Maryland **Zip:** 21201 **Location 24:** **City:** Baltimore **Country:** United States **Facility:** Johns Hopkins Hospital - Medicine - Infectious Diseases **State:** Maryland **Zip:** 21287-0005 **Location 25:** **City:** Bethesda **Country:** United States **Facility:** Walter Reed National Military Medical Center **State:** Maryland **Zip:** 20889 **Location 26:** **City:** Bethesda **Country:** United States **Facility:** National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section **State:** Maryland **Zip:** 20892-1504 **Location 27:** **City:** Boston **Country:** United States **Facility:** Massachusetts General Hospital - Infectious Diseases **State:** Massachusetts **Zip:** 02114-2621 **Location 28:** **City:** Worcester **Country:** United States **Facility:** University of Massachusetts Medical School - Infectious Diseases and Immunology **State:** Massachusetts **Zip:** 01655-0002 **Location 29:** **City:** Minneapolis **Country:** United States **Facility:** University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine **State:** Minnesota **Zip:** 55455-0341 **Location 30:** **City:** Saint Louis **Country:** United States **Facility:** Saint Louis University - Center for Vaccine Development **State:** Missouri **Zip:** 63104-1015 **Location 31:** **City:** Omaha **Country:** United States **Facility:** University of Nebraska Medical Center - Infectious Diseases **State:** Nebraska **Zip:** 68198-5400 **Location 32:** **City:** Albuquerque **Country:** United States **Facility:** University of New Mexico Clinical and Translational Science Center **State:** New Mexico **Zip:** 87106 **Location 33:** **City:** Bronx **Country:** United States **Facility:** Montefiore Medical Center - Infectious Diseases **State:** New York **Zip:** 10467-2401 **Location 34:** **City:** New York **Country:** United States **Facility:** New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology **State:** New York **Zip:** 10016 **Location 35:** **City:** Rochester **Country:** United States **Facility:** University of Rochester Medical Center - Vaccine Research Unit **State:** New York **Zip:** 14642-0001 **Location 36:** **City:** Durham **Country:** United States **Facility:** Duke Human Vaccine Institute - Duke Vaccine and Trials Unit **State:** North Carolina **Zip:** 27704 **Location 37:** **City:** Fort Bragg **Country:** United States **Facility:** Womack Army Medical Center - Pulmonary and Respiratory Services **State:** North Carolina **Zip:** 28310 **Location 38:** **City:** Portland **Country:** United States **Facility:** Kaiser Permanente Northwest - Center for Health Research **State:** Oregon **Zip:** 97227 **Location 39:** **City:** Hershey **Country:** United States **Facility:** Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases **State:** Pennsylvania **Zip:** 17033 **Location 40:** **City:** Philadelphia **Country:** United States **Facility:** University of Pennsylvania Perelman School of Medicine - Penn Institute for Immunology **State:** Pennsylvania **Zip:** 19104-4863 **Location 41:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt University Medical Center - Infectious Diseases **State:** Tennessee **Zip:** 37232-0011 **Location 42:** **City:** Dallas **Country:** United States **Facility:** Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants **State:** Texas **Zip:** 75246 **Location 43:** **City:** Dallas **Country:** United States **Facility:** University of Texas Southwestern Medical Center - Internal Medicine - Infectious Diseases **State:** Texas **Zip:** 75390-8884 **Location 44:** **City:** Fort Sam Houston **Country:** United States **Facility:** Brooke Army Medical Center **State:** Texas **Zip:** 78234 **Location 45:** **City:** Galveston **Country:** United States **Facility:** University of Texas Medical Branch - Division of Infectious Disease **State:** Texas **Zip:** 77555-0435 **Location 46:** **City:** Houston **Country:** United States **Facility:** Baylor College of Medicine - Molecular Virology and Microbiology **State:** Texas **Zip:** 77030-3411 **Location 47:** **City:** San Antonio **Country:** United States **Facility:** University of Texas Health Science Center at San Antonio - Infectious Diseases **State:** Texas **Zip:** 78229-3901 **Location 48:** **City:** Salt Lake City **Country:** United States **Facility:** University of Utah - Infectious Diseases **State:** Utah **Zip:** 84132 **Location 49:** **City:** Charlottesville **Country:** United States **Facility:** University of Virginia - Acute Care Surgery **State:** Virginia **Zip:** 22908-0816 **Location 50:** **City:** Portsmouth **Country:** United States **Facility:** Naval Medical Center Portsmouth - Infectious Disease Division **State:** Virginia **Zip:** 23708 **Location 51:** **City:** Kirkland **Country:** United States **Facility:** EvergreenHealth Infectious Disease Service **State:** Washington **Zip:** 98034 **Location 52:** **City:** Spokane **Country:** United States **Facility:** Providence Sacred Heart Medical Center **State:** Washington **Zip:** 99204 **Location 53:** **City:** Tacoma **Country:** United States **Facility:** Madigan Army Medical Center - Infectious Disease Clinic **State:** Washington **Zip:** 98431 **Location 54:** **City:** Copenhagen **Country:** Denmark **Facility:** University of Copenhagen - Centre of Excellence for Health, Immunity and Infections (CHIP) - Department of Infectious Diseases **Zip:** 2100 **Location 55:** **City:** Tokyo **Country:** Japan **Facility:** National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center **Zip:** 162-8655 **Location 56:** **City:** Bundang-gu Seongnam-si **Country:** Korea, Republic of **Facility:** Seoul National University Bundang Hospital - Division of Infectious Diseases **Zip:** 13620 **Location 57:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Seoul National University Hospital **Zip:** 03080 **Location 58:** **City:** Mexico City **Country:** Mexico **Facility:** Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia **Zip:** 14080 **Location 59:** **City:** Mexico City **Country:** Mexico **Facility:** Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas **Zip:** 14080 **Location 60:** **City:** Singapore **Country:** Singapore **Facility:** National University Health System - Division of Infectious Diseases **Zip:** 119228 **Location 61:** **City:** Singapore **Country:** Singapore **Facility:** National Centre for Infectious Diseases (NCID) **Zip:** 308442 **Location 62:** **City:** Singapore **Country:** Singapore **Facility:** Changi General Hospital - Clinical Trials and Research Unit (CTRU) **Zip:** 529889 **Location 63:** **City:** Singapore **Country:** Singapore **Facility:** Ng Teng Fong General Hospital - Infectious Disease Service **Zip:** 609606 **Location 64:** **City:** Barcelona **Country:** Spain **Facility:** Hospital Clinic Barcelona, Servicio de Salud Internacional **State:** Cataluña **Zip:** 08036 **Location 65:** **City:** Barcelona **Country:** Spain **Facility:** Hospital Germans Trias i Pujol - Servei Malalties Infeccioses **State:** Cataluña **Zip:** 08916 **Location 66:** **City:** Madrid **Country:** Spain **Facility:** Hospital Clinico San Carlos - Enfermedades Infecciosas **Zip:** 28040 **Location 67:** **City:** Brighton **Country:** United Kingdom **Facility:** Royal Sussex County Hospital - Department of Intensive Care Medicine **Location 68:** **City:** City Of London **Country:** United Kingdom **Facility:** Saint Thomas' Hospital - Directorate of Infection **Location 69:** **City:** Leeds **Country:** United Kingdom **Facility:** St. James's University Hospital - Infectious Diseases **Location 70:** **City:** Newcastle Upon Tyne **Country:** United Kingdom **Facility:** Royal Victoria Infirmary - Department of Infectious Diseases **Location 71:** **City:** Oxford **Country:** United Kingdom **Facility:** John Radcliffe Hospital ### References Module #### References **Citation:** Kramer A, Prinz C, Fichtner F, Fischer AL, Thieme V, Grundeis F, Spagl M, Seeber C, Piechotta V, Metzendorf MI, Golinski M, Moerer O, Stephani C, Mikolajewska A, Kluge S, Stegemann M, Laudi S, Skoetz N. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD015209. doi: 10.1002/14651858.CD015209. **PMID:** 35695334 **Citation:** Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2. **PMID:** 34473343 **Citation:** Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, Marconi VC, Ruiz-Palacios GM, Hsieh L, Kline S, Tapson V, Iovine NM, Jain MK, Sweeney DA, El Sahly HM, Branche AR, Regalado Pineda J, Lye DC, Sandkovsky U, Luetkemeyer AF, Cohen SH, Finberg RW, Jackson PEH, Taiwo B, Paules CI, Arguinchona H, Erdmann N, Ahuja N, Frank M, Oh MD, Kim ES, Tan SY, Mularski RA, Nielsen H, Ponce PO, Taylor BS, Larson L, Rouphael NG, Saklawi Y, Cantos VD, Ko ER, Engemann JJ, Amin AN, Watanabe M, Billings J, Elie MC, Davey RT, Burgess TH, Ferreira J, Green M, Makowski M, Cardoso A, de Bono S, Bonnett T, Proschan M, Deye GA, Dempsey W, Nayak SU, Dodd LE, Beigel JH; ACTT-2 Study Group Members. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021 Mar 4;384(9):795-807. doi: 10.1056/NEJMoa2031994. Epub 2020 Dec 11. **PMID:** 33306283 **Citation:** Azzi Y, Bartash R, Scalea J, Loarte-Campos P, Akalin E. COVID-19 and Solid Organ Transplantation: A Review Article. Transplantation. 2021 Jan 1;105(1):37-55. doi: 10.1097/TP.0000000000003523. **PMID:** 33148977 ## Document Section ### Large Document Module #### Large Docs - Date: 2020-05-25 - Filename: Prot_002.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1939179 - Type Abbrev: Prot - Upload Date: 2021-02-25T13:00 - Date: 2020-08-20 - Filename: SAP_003.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 4745170 - Type Abbrev: SAP - Upload Date: 2021-02-25T13:02 - Date: 2020-06-04 - Filename: ICF_001.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 295917 - Type Abbrev: ICF - Upload Date: 2020-08-11T09:35 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: NaAg - Name: Natriuretic Agents - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: Ot - Name: Other Dietary Supplements - Abbrev: HB - Name: Herbal and Botanical ### Intervention Browse Module - Browse Leaves - ID: M5524 - Name: Carboxymethylcellulose Sodium - Relevance: LOW - As Found: Unknown - ID: M11342 - Name: Mannitol - Relevance: LOW - As Found: Unknown - ID: M198097 - Name: Pyrazole - Relevance: LOW - As Found: Unknown - ID: M6263 - Name: Coal Tar - Relevance: LOW - As Found: Unknown - ID: M3777 - Name: Ethanol - Relevance: LOW - As Found: Unknown - ID: M341633 - Name: GS-441524 - Relevance: LOW - As Found: Unknown - ID: M223520 - Name: Titanium dioxide - Relevance: LOW - As Found: Unknown - ID: M341627 - Name: Remdesivir - Relevance: HIGH - As Found: Path - ID: M107438 - Name: Betadex - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: T404 - Name: Lecithin - Relevance: LOW - As Found: Unknown - ID: T294 - Name: Soy Bean - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000606551 - Term: Remdesivir ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2021-03-09 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Given the severity of underlying illness, participants were expected to have many symptoms and abnormalities in vital signs and laboratory values. All Grade 3 and 4 AEs were captured as AEs in this trial. Grade 2 or higher, suspected drug-related hypersensitivity reaction or deep vein thrombosis of any grade was reported as an AE in this trial. All cause mortality was calculated for the ITT population, while SAEs and AEs reflect the as treated population. #### Event Groups **Group ID:** EG000 **Title:** Remdesivir Plus Baricitinib **Deaths Num Affected:** 24 **Deaths Num At Risk:** 515 **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** EG000 **Other Num Affected:** 147 **Other Num at Risk:** 507 **Serious Number Affected:** 88 **Serious Number At Risk:** 507 **Title:** Remdesivir Plus Baricitinib **Group ID:** EG001 **Title:** Remdesivir Plus Placebo **Deaths Num Affected:** 37 **Deaths Num At Risk:** 518 **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** EG001 **Other Num Affected:** 164 **Other Num at Risk:** 509 **Serious Number Affected:** 109 **Serious Number At Risk:** 509 **Title:** Remdesivir Plus Placebo **Frequency Threshold:** 5 #### Other Events **Term:** Glomerular filtration rate decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) **Term:** Hyperglycaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Haemoglobin decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) **Term:** Lymphocyte count decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) **Term:** Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (23.0) **Term:** Blood glucose increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) **Term:** Acute kidney injury **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (23.0) #### Serious Events **Term:** Respiratory failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 29 **Num At Risk:** 507 **Num Events:** 30 **Group ID:** EG001 **Num Affected:** 37 **Num At Risk:** 509 **Num Events:** 38 **Term:** Acute respiratory failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 18 **Num At Risk:** 507 **Num Events:** 18 **Group ID:** EG001 **Num Affected:** 16 **Num At Risk:** 509 **Num Events:** 16 **Term:** Acute kidney injury **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 5 **Num At Risk:** 507 **Num Events:** 5 **Group ID:** EG001 **Num Affected:** 11 **Num At Risk:** 509 **Num Events:** 11 **Term:** Acute respiratory distress syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 507 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 10 **Num At Risk:** 509 **Num Events:** 10 **Term:** Septic shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 507 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 8 **Num At Risk:** 509 **Num Events:** 8 **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 6 **Num At Risk:** 507 **Num Events:** 6 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 509 **Num Events:** 5 **Term:** Respiratory distress **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 7 **Num At Risk:** 507 **Num Events:** 8 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 509 **Num Events:** 7 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 507 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 8 **Num At Risk:** 509 **Num Events:** 8 **Term:** Multiple organ dysfunction syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 507 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 509 **Num Events:** 6 **Term:** Pulmonary embolism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 5 **Num At Risk:** 507 **Num Events:** 5 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Hypoxia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 507 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 509 **Num Events:** 4 **Term:** Shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 507 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 509 **Num Events:** 4 **Term:** Cardiac arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 507 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 509 **Num Events:** 3 **Term:** Dyspnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 507 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 509 **Num Events:** 4 **Term:** Pneumothorax **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 509 **Num Events:** 4 **Term:** Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 507 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 509 **Num Events:** 5 **Term:** Renal failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 509 **Num Events:** 5 **Term:** Pulseless electrical activity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 507 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 509 **Num Events:** 2 **Term:** Cerebrovascular accident **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 509 **Num Events:** 2 **Term:** Encephalopathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 509 **Num Events:** 2 **Term:** Alanine aminotransferase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 509 **Num Events:** 3 **Term:** Chest pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 507 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Cardio-respiratory arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Deep vein thrombosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Respiratory arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Aspartate aminotransferase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 509 **Num Events:** 2 **Term:** Asthenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Cardiac failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Distributive shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Gastrointestinal haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Guillain-Barre syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Intervertebral discitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Leukopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Lower respiratory tract infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Lymphocyte count decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Nervous system disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Non-cardiac chest pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Pneumonia aspiration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Procedural hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Prostatic abscess **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Sickle cell anaemia with crisis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Sinus tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Thrombophlebitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Urinary tract infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Visual impairment **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Term:** Abdominal pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Acidosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Aortic valve stenosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Arrhythmia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Aspergillus infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Atrial fibrillation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Atrioventricular block **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Blood creatinine increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Blood glucose decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Bradycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Diabetic ketoacidosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Embolism venous **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Endotracheal intubation complication **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 2 **Term:** Fall **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Haematoma muscle **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Haemoglobin decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Haemorrhage intracranial **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Hepatic haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Hepatitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Hyperkalaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Hypersensitivity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Hypoglycaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Injection site induration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Left ventricular failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Lung abscess **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Lymphopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Metabolic acidosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Oedema peripheral **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Overdose **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Pneumomediastinum **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Presyncope **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Right ventricular dysfunction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Subdural haematoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Tachypnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 509 **Num Events:** 2 **Term:** Troponin increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Urosepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 507 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 509 **Num Events:** 1 **Term:** Lipoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (23.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 507 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 509 **Time Frame:** Serious and Grade 3 and 4 non-serious adverse events were collected for 29 days after the first dose. Laboratory values were systematically assessed at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29. Treatment emergent and fatal AEs are reported. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 515 **Group ID:** BG001 **Value:** 518 **Group ID:** BG002 **Value:** 1033 **Units:** Participants ### Group **ID:** BG000 **Title:** Remdesivir Plus Baricitinib **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. ### Group **ID:** BG001 **Title:** Remdesivir Plus Placebo **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 368 #### Measurement **Group ID:** BG001 **Value:** 360 #### Measurement **Group ID:** BG002 **Value:** 728 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 147 #### Measurement **Group ID:** BG001 **Value:** 158 #### Measurement **Group ID:** BG002 **Value:** 305 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 15.4 **Value:** 55.0 #### Measurement **Group ID:** BG001 **Spread:** 16.0 **Value:** 55.8 #### Measurement **Group ID:** BG002 **Spread:** 15.7 **Value:** 55.4 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 196 #### Measurement **Group ID:** BG001 **Value:** 185 #### Measurement **Group ID:** BG002 **Value:** 381 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 319 #### Measurement **Group ID:** BG001 **Value:** 333 #### Measurement **Group ID:** BG002 **Value:** 652 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 263 #### Measurement **Group ID:** BG001 **Value:** 268 #### Measurement **Group ID:** BG002 **Value:** 531 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 246 #### Measurement **Group ID:** BG001 **Value:** 240 #### Measurement **Group ID:** BG002 **Value:** 486 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 16 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 10 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 49 #### Measurement **Group ID:** BG001 **Value:** 52 #### Measurement **Group ID:** BG002 **Value:** 101 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 11 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 77 #### Measurement **Group ID:** BG001 **Value:** 79 #### Measurement **Group ID:** BG002 **Value:** 156 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 251 #### Measurement **Group ID:** BG001 **Value:** 245 #### Measurement **Group ID:** BG002 **Value:** 496 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 132 #### Measurement **Group ID:** BG001 **Value:** 127 #### Measurement **Group ID:** BG002 **Value:** 259 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 22 **Class Title:** South Korea #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 22 #### Measurement **Group ID:** BG002 **Value:** 44 **Class Title:** Singapore #### Measurement **Group ID:** BG000 **Value:** 441 #### Measurement **Group ID:** BG001 **Value:** 444 #### Measurement **Group ID:** BG002 **Value:** 885 **Class Title:** United States #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Class Title:** Japan #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 9 **Class Title:** Denmark #### Measurement **Group ID:** BG000 **Value:** 35 #### Measurement **Group ID:** BG001 **Value:** 33 #### Measurement **Group ID:** BG002 **Value:** 68 **Class Title:** Mexico #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Class Title:** United Kingdom #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 **Class Title:** Spain ### Measure #### Measurement **Group ID:** BG000 **Value:** 176 #### Measurement **Group ID:** BG001 **Value:** 191 #### Measurement **Group ID:** BG002 **Value:** 367 **Category Title:** Severe Disease Severity #### Measurement **Group ID:** BG000 **Value:** 339 #### Measurement **Group ID:** BG001 **Value:** 327 #### Measurement **Group ID:** BG002 **Value:** 666 **Category Title:** Moderate Disease Severity **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 6 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Region of Enrollment **Unit of Measure:** Participants ### Measure 7 **Description:** Severe disease was defined as hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive or non-invasive ventilation, or high flow oxygen Moderate disease was defined as hospitalized, requiring supplemental oxygen or not requiring supplemental oxygen. Disease severity was as defined at the time or randomization. **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Disease severity **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** LTE60 **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** NIAID **Phone:** 3014519881 **Title:** John Beigel, MD ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 1.00 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.31 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.047 **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.15 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ### Outcome Measure 17 #### Analysis **CI Lower Limit:** -12 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Risk Difference (RD) **Parameter Value:** -6 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 18 #### Analysis **CI Lower Limit:** -10 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Risk Difference (RD) **Parameter Value:** -5 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 19 ### Outcome Measure 20 ### Outcome Measure 21 ### Outcome Measure 22 ### Outcome Measure 23 ### Outcome Measure 24 ### Outcome Measure 25 ### Outcome Measure 26 ### Outcome Measure 27 ### Outcome Measure 28 #### Analysis **CI Lower Limit:** 1.01 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.57 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.44 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.26 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 29 ### Outcome Measure 30 ### Outcome Measure 31 ### Outcome Measure 32 ### Outcome Measure 33 ### Outcome Measure 34 ### Outcome Measure 35 ### Outcome Measure 36 ### Outcome Measure 37 ### Outcome Measure 38 #### Analysis **CI Lower Limit:** 1.06 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.39 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.002 **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.21 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 39 #### Analysis **CI Lower Limit:** 1.05 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.38 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.005 **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.20 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 40 #### Analysis **CI Lower Limit:** 1.07 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.44 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.003 **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.24 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 41 ### Outcome Measure 42 ### Outcome Measure 43 #### Analysis **CI Lower Limit:** 0.73 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.68 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** This analysis is for Asian participants. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.11 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.75 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.50 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** This analysis is for Black or African American participants. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.06 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.93 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.37 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** This analysis is for White participants. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.13 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.03 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.74 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** This analysis is for Race of Other participants. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.34 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 44 #### Analysis **CI Lower Limit:** 1.08 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.60 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** This analysis is for Not Hispanic or Latino participants **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.31 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.89 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.31 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** This analysis is for Hispanic or Latino participants. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.08 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 45 #### Analysis **CI Lower Limit:** 1.04 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.46 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** This analysis is for Male participants. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.23 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.85 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.32 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** This analysis is for Female participants. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 1.06 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.0 - **Spread:** - **Upper Limit:** 9.0 - **Value:** 8.0 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 37.1 - **Upper Limit:** - **Value:** 3.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 30.1 - **Upper Limit:** - **Value:** 2.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 491 - **Group ID:** OG001 - **Value:** 491 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 104.4 - **Upper Limit:** - **Value:** 16.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 40.9 - **Upper Limit:** - **Value:** 8.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 407 - **Group ID:** OG001 - **Value:** 406 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 45.2 - **Upper Limit:** - **Value:** 7.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 46.9 - **Upper Limit:** - **Value:** 7.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 268 - **Group ID:** OG001 - **Value:** 284 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 37.5 - **Upper Limit:** - **Value:** 0.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 70.2 - **Upper Limit:** - **Value:** 7.3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 187 - **Group ID:** OG001 - **Value:** 201 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 61.5 - **Upper Limit:** - **Value:** 5.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 55.1 - **Upper Limit:** - **Value:** 3.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 250 - **Group ID:** OG001 - **Value:** 270 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 43.0 - **Upper Limit:** - **Value:** -5.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 116.1 - **Upper Limit:** - **Value:** 2.3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 256 - **Group ID:** OG001 - **Value:** 255 **Units:** Participants #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 72.4 - **Upper Limit:** - **Value:** 3.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 126.4 - **Upper Limit:** - **Value:** 2.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 486 - **Group ID:** OG001 - **Value:** 487 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 413.1 - **Upper Limit:** - **Value:** 27.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 48.3 - **Upper Limit:** - **Value:** 2.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 404 - **Group ID:** OG001 - **Value:** 403 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 38.4 - **Upper Limit:** - **Value:** -5.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 42.3 - **Upper Limit:** - **Value:** -4.3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 265 - **Group ID:** OG001 - **Value:** 282 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 46.4 - **Upper Limit:** - **Value:** -10.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 208.3 - **Upper Limit:** - **Value:** 6.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 185 - **Group ID:** OG001 - **Value:** 200 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 110.1 - **Upper Limit:** - **Value:** -6.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 91.0 - **Upper Limit:** - **Value:** -3.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 246 - **Group ID:** OG001 - **Value:** 266 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 46.7 - **Upper Limit:** - **Value:** -17.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 291.1 - **Upper Limit:** - **Value:** 2.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 251 - **Group ID:** OG001 - **Value:** 251 **Units:** Participants #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.465 - **Upper Limit:** - **Value:** -0.036 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.362 - **Upper Limit:** - **Value:** -0.019 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 494 - **Group ID:** OG001 - **Value:** 495 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.475 - **Upper Limit:** - **Value:** -0.078 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.556 - **Upper Limit:** - **Value:** 0.001 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 412 - **Group ID:** OG001 - **Value:** 410 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.570 - **Upper Limit:** - **Value:** -0.082 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.958 - **Upper Limit:** - **Value:** 0.129 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 270 - **Group ID:** OG001 - **Value:** 285 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.798 - **Upper Limit:** - **Value:** -0.055 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.037 - **Upper Limit:** - **Value:** 0.194 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 190 - **Group ID:** OG001 - **Value:** 202 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.714 - **Upper Limit:** - **Value:** -0.042 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.662 - **Upper Limit:** - **Value:** 0.094 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 254 - **Group ID:** OG001 - **Value:** 273 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.678 - **Upper Limit:** - **Value:** -0.034 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.511 - **Upper Limit:** - **Value:** 0.033 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 260 - **Group ID:** OG001 - **Value:** 257 **Units:** Participants #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 56.4 - **Upper Limit:** - **Value:** -17.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 54.0 - **Upper Limit:** - **Value:** -6.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 493 - **Group ID:** OG001 - **Value:** 493 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 59.7 - **Upper Limit:** - **Value:** -15.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 58.4 - **Upper Limit:** - **Value:** -1.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 412 - **Group ID:** OG001 - **Value:** 409 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 78.9 - **Upper Limit:** - **Value:** -16.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 73.7 - **Upper Limit:** - **Value:** 5.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 270 - **Group ID:** OG001 - **Value:** 284 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 72.3 - **Upper Limit:** - **Value:** -8.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 66.2 - **Upper Limit:** - **Value:** 1.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 190 - **Group ID:** OG001 - **Value:** 203 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 69.8 - **Upper Limit:** - **Value:** -11.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 68.3 - **Upper Limit:** - **Value:** 0.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 252 - **Group ID:** OG001 - **Value:** 271 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 66.5 - **Upper Limit:** - **Value:** -4.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 60.3 - **Upper Limit:** - **Value:** -2.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 257 - **Group ID:** OG001 - **Value:** 256 **Units:** Participants #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.05 - **Upper Limit:** - **Value:** -0.46 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.51 - **Upper Limit:** - **Value:** -0.34 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 493 - **Group ID:** OG001 - **Value:** 494 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.23 - **Upper Limit:** - **Value:** -0.62 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.13 - **Upper Limit:** - **Value:** -0.64 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 410 - **Group ID:** OG001 - **Value:** 409 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.61 - **Upper Limit:** - **Value:** -0.93 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.47 - **Upper Limit:** - **Value:** -1.08 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 270 - **Group ID:** OG001 - **Value:** 284 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.85 - **Upper Limit:** - **Value:** -1.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.88 - **Upper Limit:** - **Value:** -1.62 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 189 - **Group ID:** OG001 - **Value:** 199 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.87 - **Upper Limit:** - **Value:** -0.96 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.38 - **Upper Limit:** - **Value:** -1.12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 253 - **Group ID:** OG001 - **Value:** 267 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.87 - **Upper Limit:** - **Value:** -0.54 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.25 - **Upper Limit:** - **Value:** -0.77 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 260 - **Group ID:** OG001 - **Value:** 254 **Units:** Participants #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 54.0 - **Upper Limit:** - **Value:** 55.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 51.6 - **Upper Limit:** - **Value:** 52.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 493 - **Group ID:** OG001 - **Value:** 494 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 87.8 - **Upper Limit:** - **Value:** 116.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 86.9 - **Upper Limit:** - **Value:** 106.1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 410 - **Group ID:** OG001 - **Value:** 409 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 137.4 - **Upper Limit:** - **Value:** 197.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 128.5 - **Upper Limit:** - **Value:** 158.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 269 - **Group ID:** OG001 - **Value:** 284 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 156.0 - **Upper Limit:** - **Value:** 229.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 146.4 - **Upper Limit:** - **Value:** 145.7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 189 - **Group ID:** OG001 - **Value:** 199 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 158.8 - **Upper Limit:** - **Value:** 175.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 134.9 - **Upper Limit:** - **Value:** 111.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 252 - **Group ID:** OG001 - **Value:** 267 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 95.8 - **Upper Limit:** - **Value:** 16.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 107.9 - **Upper Limit:** - **Value:** 36.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 260 - **Group ID:** OG001 - **Value:** 254 **Units:** Participants #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.13 - **Upper Limit:** - **Value:** -0.03 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.59 - **Upper Limit:** - **Value:** 0.05 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 447 - **Group ID:** OG001 - **Value:** 439 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.25 - **Upper Limit:** - **Value:** 0.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.65 - **Upper Limit:** - **Value:** 0.08 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 360 - **Group ID:** OG001 - **Value:** 370 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.96 - **Upper Limit:** - **Value:** 0.01 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.98 - **Upper Limit:** - **Value:** 0.08 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 244 - **Group ID:** OG001 - **Value:** 250 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.65 - **Upper Limit:** - **Value:** 0.04 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.04 - **Upper Limit:** - **Value:** 0.03 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 162 - **Group ID:** OG001 - **Value:** 175 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** -0.04 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.91 - **Upper Limit:** - **Value:** -0.08 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 222 - **Group ID:** OG001 - **Value:** 241 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.55 - **Upper Limit:** - **Value:** -0.12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.99 - **Upper Limit:** - **Value:** -0.03 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 232 - **Group ID:** OG001 - **Value:** 232 **Units:** Participants #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.32 - **Upper Limit:** - **Value:** -0.06 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.43 - **Upper Limit:** - **Value:** -0.01 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 490 - **Group ID:** OG001 - **Value:** 491 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.37 - **Upper Limit:** - **Value:** -0.04 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.42 - **Upper Limit:** - **Value:** 0.01 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 407 - **Group ID:** OG001 - **Value:** 405 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** -0.06 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.66 - **Upper Limit:** - **Value:** 0.01 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 268 - **Group ID:** OG001 - **Value:** 284 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.43 - **Upper Limit:** - **Value:** -0.08 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.19 - **Upper Limit:** - **Value:** 0.08 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 187 - **Group ID:** OG001 - **Value:** 201 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.37 - **Upper Limit:** - **Value:** -0.10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.20 - **Upper Limit:** - **Value:** 0.08 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 250 - **Group ID:** OG001 - **Value:** 270 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.36 - **Upper Limit:** - **Value:** -0.10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.91 - **Upper Limit:** - **Value:** 0.01 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 256 - **Group ID:** OG001 - **Value:** 254 **Units:** Participants #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.020 - **Upper Limit:** - **Value:** -0.831 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.588 - **Upper Limit:** - **Value:** -0.037 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 493 - **Group ID:** OG001 - **Value:** 494 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.399 - **Upper Limit:** - **Value:** -0.276 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.238 - **Upper Limit:** - **Value:** 0.392 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 410 - **Group ID:** OG001 - **Value:** 409 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.006 - **Upper Limit:** - **Value:** 0.663 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.536 - **Upper Limit:** - **Value:** 1.606 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 270 - **Group ID:** OG001 - **Value:** 284 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.683 - **Upper Limit:** - **Value:** 1.869 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.419 - **Upper Limit:** - **Value:** 2.938 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 189 - **Group ID:** OG001 - **Value:** 199 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.125 - **Upper Limit:** - **Value:** 0.694 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.741 - **Upper Limit:** - **Value:** 2.162 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 253 - **Group ID:** OG001 - **Value:** 267 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.532 - **Upper Limit:** - **Value:** -0.364 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.176 - **Upper Limit:** - **Value:** 0.712 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 260 - **Group ID:** OG001 - **Value:** 254 **Units:** Participants #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.234 - **Upper Limit:** - **Value:** -1.925 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.787 - **Upper Limit:** - **Value:** -0.333 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 488 - **Group ID:** OG001 - **Value:** 493 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.092 - **Upper Limit:** - **Value:** -1.334 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.630 - **Upper Limit:** - **Value:** -0.204 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 408 - **Group ID:** OG001 - **Value:** 404 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.695 - **Upper Limit:** - **Value:** -0.813 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.665 - **Upper Limit:** - **Value:** 1.139 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 268 - **Group ID:** OG001 - **Value:** 282 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.881 - **Upper Limit:** - **Value:** -0.046 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.152 - **Upper Limit:** - **Value:** 1.847 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 186 - **Group ID:** OG001 - **Value:** 196 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.844 - **Upper Limit:** - **Value:** -1.192 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.995 - **Upper Limit:** - **Value:** 1.414 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 249 - **Group ID:** OG001 - **Value:** 267 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.735 - **Upper Limit:** - **Value:** -1.708 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.205 - **Upper Limit:** - **Value:** -0.656 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 257 - **Group ID:** OG001 - **Value:** 253 **Units:** Participants #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.290 - **Upper Limit:** - **Value:** 0.503 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.844 - **Upper Limit:** - **Value:** 0.074 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 488 - **Group ID:** OG001 - **Value:** 493 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.540 - **Upper Limit:** - **Value:** 0.620 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.838 - **Upper Limit:** - **Value:** 0.205 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 408 - **Group ID:** OG001 - **Value:** 404 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.094 - **Upper Limit:** - **Value:** 0.515 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.366 - **Upper Limit:** - **Value:** 0.304 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 268 - **Group ID:** OG001 - **Value:** 282 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.204 - **Upper Limit:** - **Value:** 0.541 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.709 - **Upper Limit:** - **Value:** 0.409 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 186 - **Group ID:** OG001 - **Value:** 196 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.579 - **Upper Limit:** - **Value:** 0.687 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.684 - **Upper Limit:** - **Value:** 0.718 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 249 - **Group ID:** OG001 - **Value:** 267 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.293 - **Upper Limit:** - **Value:** 0.653 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.996 - **Upper Limit:** - **Value:** 0.927 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 257 - **Group ID:** OG001 - **Value:** 253 **Units:** Participants #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.810 - **Upper Limit:** - **Value:** 0.004 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.750 - **Upper Limit:** - **Value:** 0.062 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 487 - **Group ID:** OG001 - **Value:** 493 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.053 - **Upper Limit:** - **Value:** 0.094 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.013 - **Upper Limit:** - **Value:** 0.153 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 408 - **Group ID:** OG001 - **Value:** 404 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.948 - **Upper Limit:** - **Value:** 0.105 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.758 - **Upper Limit:** - **Value:** 0.279 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 268 - **Group ID:** OG001 - **Value:** 282 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.439 - **Upper Limit:** - **Value:** 0.210 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.512 - **Upper Limit:** - **Value:** 0.378 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 186 - **Group ID:** OG001 - **Value:** 196 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.591 - **Upper Limit:** - **Value:** 0.256 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.606 - **Upper Limit:** - **Value:** 0.329 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 249 - **Group ID:** OG001 - **Value:** 267 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.434 - **Upper Limit:** - **Value:** 0.108 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.745 - **Upper Limit:** - **Value:** 0.212 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 257 - **Group ID:** OG001 - **Value:** 253 **Units:** Participants #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.039 - **Upper Limit:** - **Value:** 0.000 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.050 - **Upper Limit:** - **Value:** 0.001 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 483 - **Group ID:** OG001 - **Value:** 492 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.070 - **Upper Limit:** - **Value:** 0.007 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.044 - **Upper Limit:** - **Value:** 0.006 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 402 - **Group ID:** OG001 - **Value:** 402 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.055 - **Upper Limit:** - **Value:** 0.011 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.075 - **Upper Limit:** - **Value:** 0.017 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 265 - **Group ID:** OG001 - **Value:** 281 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.063 - **Upper Limit:** - **Value:** 0.014 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.063 - **Upper Limit:** - **Value:** 0.022 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 185 - **Group ID:** OG001 - **Value:** 195 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.085 - **Upper Limit:** - **Value:** 0.026 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.104 - **Upper Limit:** - **Value:** 0.037 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 247 - **Group ID:** OG001 - **Value:** 265 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.045 - **Upper Limit:** - **Value:** 0.022 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.092 - **Upper Limit:** - **Value:** 0.036 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 257 - **Group ID:** OG001 - **Value:** 250 **Units:** Participants #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.135 - **Upper Limit:** - **Value:** 0.050 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.201 - **Upper Limit:** - **Value:** 0.039 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 484 - **Group ID:** OG001 - **Value:** 492 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.402 - **Upper Limit:** - **Value:** 0.104 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.257 - **Upper Limit:** - **Value:** 0.075 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 405 - **Group ID:** OG001 - **Value:** 403 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.126 - **Upper Limit:** - **Value:** 0.088 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.232 - **Upper Limit:** - **Value:** 0.086 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 265 - **Group ID:** OG001 - **Value:** 281 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.119 - **Upper Limit:** - **Value:** 0.078 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.299 - **Upper Limit:** - **Value:** 0.115 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 185 - **Group ID:** OG001 - **Value:** 195 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.231 - **Upper Limit:** - **Value:** 0.121 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.163 - **Upper Limit:** - **Value:** 0.109 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 247 - **Group ID:** OG001 - **Value:** 264 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.171 - **Upper Limit:** - **Value:** 0.192 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.267 - **Upper Limit:** - **Value:** 0.205 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 257 - **Group ID:** OG001 - **Value:** 251 **Units:** Participants #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.5 - **Upper Limit:** - **Value:** -0.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.6 - **Upper Limit:** - **Value:** -0.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.8 - **Upper Limit:** - **Value:** -0.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.8 - **Upper Limit:** - **Value:** -0.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.9 - **Upper Limit:** - **Value:** -1.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.3 - **Upper Limit:** - **Value:** -0.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.2 - **Upper Limit:** - **Value:** -1.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.5 - **Upper Limit:** - **Value:** -1.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.3 - **Upper Limit:** - **Value:** -2.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.9 - **Upper Limit:** - **Value:** -1.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.8 - **Upper Limit:** - **Value:** -2.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.6 - **Upper Limit:** - **Value:** -1.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.3 - **Upper Limit:** - **Value:** -2.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.0 - **Upper Limit:** - **Value:** -1.4 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 36.5 - **Spread:** - **Upper Limit:** 45.3 - **Value:** 40.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 42.4 - **Spread:** - **Upper Limit:** 51.2 - **Value:** 46.8 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12.9 - **Spread:** - **Upper Limit:** 19.5 - **Value:** 16.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 17.6 - **Spread:** - **Upper Limit:** 24.8 - **Value:** 21.0 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 15 - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 20 - **Value:** 8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 515 - **Group ID:** OG001 - **Value:** 518 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 13 - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 15 - **Value:** 8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 491 - **Group ID:** OG001 - **Value:** 481 **Units:** Participants #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 15 - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 11 - **Value:** 4.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 70 - **Group ID:** OG001 - **Value:** 82 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 10 - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 7 - **Value:** 4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 65 - **Group ID:** OG001 - **Value:** 72 **Units:** Participants #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 4 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 6 - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 4 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 6 - **Value:** 3 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8 - **Spread:** - **Upper Limit:** 28 - **Value:** 16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 12 - **Spread:** - **Upper Limit:** 28 - **Value:** 27 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 46 - **Group ID:** OG001 - **Value:** 70 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6 - **Spread:** - **Upper Limit:** 22 - **Value:** 13 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 10 - **Spread:** - **Upper Limit:** 27 - **Value:** 20 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 39 - **Group ID:** OG001 - **Value:** 52 **Units:** Participants #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4 - **Spread:** - **Upper Limit:** 27 - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4 - **Spread:** - **Upper Limit:** 28 - **Value:** 12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 445 - **Group ID:** OG001 - **Value:** 446 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4 - **Spread:** - **Upper Limit:** 24 - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4 - **Spread:** - **Upper Limit:** 28 - **Value:** 10 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 421 - **Group ID:** OG001 - **Value:** 409 **Units:** Participants #### Outcome Measure 24 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 50 - **Spread:** - **Upper Limit:** 59 - **Value:** 55 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 47 - **Spread:** - **Upper Limit:** 55 - **Value:** 51 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 62 - **Spread:** - **Upper Limit:** 70 - **Value:** 66 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 55 - **Spread:** - **Upper Limit:** 64 - **Value:** 59 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 4 - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 13 - **Spread:** - **Upper Limit:** 20 - **Value:** 16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 14 - **Spread:** - **Upper Limit:** 21 - **Value:** 18 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 20 - **Spread:** - **Upper Limit:** 27 - **Value:** 23 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 23 - **Spread:** - **Upper Limit:** 31 - **Value:** 27 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 26 - **Spread:** - **Upper Limit:** 34 - **Value:** 30 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 30 - **Spread:** - **Upper Limit:** 38 - **Value:** 34 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 6 - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 6 - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 7 - **Value:** 5 **Title:** #### Outcome Measure 25 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8 - **Spread:** - **Upper Limit:** 13 - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 12 - **Spread:** - **Upper Limit:** 19 - **Value:** 15 **Title:** #### Outcome Measure 26 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 15 - **Spread:** - **Upper Limit:** 34 - **Value:** 23 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 30 - **Spread:** - **Upper Limit:** 52 - **Value:** 40 **Title:** #### Outcome Measure 27 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.5 - **Upper Limit:** - **Value:** 0.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.6 - **Upper Limit:** - **Value:** 0.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.7 - **Upper Limit:** - **Value:** 0.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.7 - **Upper Limit:** - **Value:** 0.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.9 - **Upper Limit:** - **Value:** -0.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.9 - **Upper Limit:** - **Value:** -0.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.0 - **Upper Limit:** - **Value:** -0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.0 - **Upper Limit:** - **Value:** -0.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -2.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.0 - **Upper Limit:** - **Value:** -1.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -2.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** -2.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -2.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** -2.5 **Title:** #### Outcome Measure 28 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 4 - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7 - **Spread:** - **Upper Limit:** 12 - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 13 - **Spread:** - **Upper Limit:** 19 - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 6 - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 6 - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6 - **Spread:** - **Upper Limit:** 11 - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7 - **Spread:** - **Upper Limit:** 13 - **Value:** 10 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4 - **Spread:** - **Upper Limit:** 8 - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 30 - **Spread:** - **Upper Limit:** 39 - **Value:** 34 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 28 - **Spread:** - **Upper Limit:** 36 - **Value:** 31 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 30 - **Spread:** - **Upper Limit:** 39 - **Value:** 34 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 28 - **Spread:** - **Upper Limit:** 36 - **Value:** 32 **Title:** #### Outcome Measure 29 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8 - **Spread:** - **Upper Limit:** 13 - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 9 - **Spread:** - **Upper Limit:** 14 - **Value:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 17 - **Spread:** - **Upper Limit:** 24 - **Value:** 20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 18 - **Spread:** - **Upper Limit:** 26 - **Value:** 22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 52 - **Spread:** - **Upper Limit:** 60 - **Value:** 56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 49 - **Spread:** - **Upper Limit:** 58 - **Value:** 53 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 11 - **Spread:** - **Upper Limit:** 17 - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 11 - **Spread:** - **Upper Limit:** 17 - **Value:** 14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** #### Outcome Measure 30 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12 - **Spread:** - **Upper Limit:** 18 - **Value:** 15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 13 - **Spread:** - **Upper Limit:** 20 - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 18 - **Spread:** - **Upper Limit:** 25 - **Value:** 22 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 18 - **Spread:** - **Upper Limit:** 25 - **Value:** 22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 41 - **Spread:** - **Upper Limit:** 50 - **Value:** 45 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 40 - **Spread:** - **Upper Limit:** 49 - **Value:** 44 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 13 - **Spread:** - **Upper Limit:** 20 - **Value:** 16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 12 - **Spread:** - **Upper Limit:** 18 - **Value:** 14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 4 - **Value:** 2 **Title:** #### Outcome Measure 31 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12 - **Spread:** - **Upper Limit:** 19 - **Value:** 15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 15 - **Spread:** - **Upper Limit:** 21 - **Value:** 18 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 14 - **Spread:** - **Upper Limit:** 20 - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 15 - **Spread:** - **Upper Limit:** 22 - **Value:** 18 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 31 - **Spread:** - **Upper Limit:** 39 - **Value:** 35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 29 - **Spread:** - **Upper Limit:** 37 - **Value:** 33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 16 - **Spread:** - **Upper Limit:** 22 - **Value:** 19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 12 - **Spread:** - **Upper Limit:** 18 - **Value:** 15 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8 - **Spread:** - **Upper Limit:** 13 - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 10 - **Spread:** - **Upper Limit:** 16 - **Value:** 13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 4 - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 **Title:** #### Outcome Measure 32 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 11 - **Spread:** - **Upper Limit:** 17 - **Value:** 13 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 15 - **Spread:** - **Upper Limit:** 22 - **Value:** 18 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8 - **Spread:** - **Upper Limit:** 14 - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 9 - **Spread:** - **Upper Limit:** 15 - **Value:** 12 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 15 - **Spread:** - **Upper Limit:** 22 - **Value:** 18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 15 - **Spread:** - **Upper Limit:** 22 - **Value:** 18 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 10 - **Spread:** - **Upper Limit:** 16 - **Value:** 12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7 - **Spread:** - **Upper Limit:** 13 - **Value:** 10 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 35 - **Spread:** - **Upper Limit:** 44 - **Value:** 40 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 32 - **Spread:** - **Upper Limit:** 41 - **Value:** 36 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 6 - **Value:** 4 **Title:** #### Outcome Measure 33 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 4 - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 9 - **Spread:** - **Upper Limit:** 14 - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 13 - **Spread:** - **Upper Limit:** 20 - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 9 - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 9 - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 10 - **Spread:** - **Upper Limit:** 15 - **Value:** 12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 8 - **Spread:** - **Upper Limit:** 13 - **Value:** 10 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6 - **Spread:** - **Upper Limit:** 11 - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 9 - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 0.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 52 - **Spread:** - **Upper Limit:** 60 - **Value:** 56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 48 - **Spread:** - **Upper Limit:** 56 - **Value:** 52 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 6 - **Value:** 4 **Title:** #### Outcome Measure 34 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 6 - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 9 - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4 - **Spread:** - **Upper Limit:** 8 - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7 - **Spread:** - **Upper Limit:** 12 - **Value:** 9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 7 - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 4 - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 4 - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 21 - **Spread:** - **Upper Limit:** 28 - **Value:** 24 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 21 - **Spread:** - **Upper Limit:** 29 - **Value:** 25 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 40 - **Spread:** - **Upper Limit:** 49 - **Value:** 44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 33 - **Spread:** - **Upper Limit:** 42 - **Value:** 37 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 6 - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6 - **Spread:** - **Upper Limit:** 11 - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 8 - **Spread:** - **Upper Limit:** 13 - **Value:** 10 **Title:** #### Outcome Measure 35 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 7 - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 10 - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 9 - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 4 - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 5 - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 2 - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 20 - **Spread:** - **Upper Limit:** 27 - **Value:** 23 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 20 - **Spread:** - **Upper Limit:** 27 - **Value:** 23 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 44 - **Spread:** - **Upper Limit:** 53 - **Value:** 49 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 39 - **Spread:** - **Upper Limit:** 47 - **Value:** 43 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1 - **Spread:** - **Upper Limit:** 3 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 9 - **Spread:** - **Upper Limit:** 15 - **Value:** 12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 10 - **Spread:** - **Upper Limit:** 16 - **Value:** 13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 1 - **Value:** 0.2 **Title:** #### Outcome Measure 36 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.01 - **Spread:** - **Upper Limit:** 0.03 - **Value:** 0.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.02 - **Spread:** - **Upper Limit:** 0.05 - **Value:** 0.03 **Title:** #### Outcome Measure 37 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.03 - **Spread:** - **Upper Limit:** 0.08 - **Value:** 0.05 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.06 - **Spread:** - **Upper Limit:** 0.11 - **Value:** 0.08 **Title:** #### Outcome Measure 38 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5.0 - **Spread:** - **Upper Limit:** 7.0 - **Value:** 6.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.0 - **Spread:** - **Upper Limit:** 9.0 - **Value:** 8.0 **Title:** #### Outcome Measure 39 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12.0 - **Spread:** - **Upper Limit:** 13.0 - **Value:** 12.0 - **Comment:** Due to a large number of subjects improving 13 days post randomization there is little variability at the 50th percentile and the methodology described by Klein and Moeschberger (1997) is unable to compute a confidence interval - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** 13.0 **Title:** #### Outcome Measure 40 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 7.0 - **Value:** 6.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 9.0 - **Value:** 7.0 **Title:** #### Outcome Measure 41 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 169.442 - **Upper Limit:** - **Value:** -23.035 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 102.661 - **Upper Limit:** - **Value:** -18.671 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 446 - **Group ID:** OG001 - **Value:** 455 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 110.364 - **Upper Limit:** - **Value:** -58.935 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 150.076 - **Upper Limit:** - **Value:** -30.908 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 368 - **Group ID:** OG001 - **Value:** 367 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 104.943 - **Upper Limit:** - **Value:** -78.411 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 125.254 - **Upper Limit:** - **Value:** -62.038 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 241 - **Group ID:** OG001 - **Value:** 250 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 124.751 - **Upper Limit:** - **Value:** -103.789 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 159.184 - **Upper Limit:** - **Value:** -88.881 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 159 - **Group ID:** OG001 - **Value:** 181 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 110.502 - **Upper Limit:** - **Value:** -122.339 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 155.762 - **Upper Limit:** - **Value:** -112.588 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 221 - **Group ID:** OG001 - **Value:** 240 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 115.243 - **Upper Limit:** - **Value:** -131.333 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 268.733 - **Upper Limit:** - **Value:** -122.342 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 217 - **Group ID:** OG001 - **Value:** 219 **Units:** Participants #### Outcome Measure 42 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.062 - **Upper Limit:** - **Value:** -0.374 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.663 - **Upper Limit:** - **Value:** 0.384 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 436 - **Group ID:** OG001 - **Value:** 432 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.968 - **Upper Limit:** - **Value:** 0.053 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.978 - **Upper Limit:** - **Value:** -0.149 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 352 - **Group ID:** OG001 - **Value:** 347 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.994 - **Upper Limit:** - **Value:** -0.271 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.387 - **Upper Limit:** - **Value:** 0.351 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 227 - **Group ID:** OG001 - **Value:** 230 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.779 - **Upper Limit:** - **Value:** 0.622 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.283 - **Upper Limit:** - **Value:** 0.309 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 153 - **Group ID:** OG001 - **Value:** 160 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.352 - **Upper Limit:** - **Value:** -0.988 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.579 - **Upper Limit:** - **Value:** -0.422 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 215 - **Group ID:** OG001 - **Value:** 230 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 27.229 - **Upper Limit:** - **Value:** 0.774 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.386 - **Upper Limit:** - **Value:** -0.219 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 223 - **Group ID:** OG001 - **Value:** 206 **Units:** Participants #### Outcome Measure 43 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7.0 - **Spread:** - **Upper Limit:** 13.0 - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 9.0 - **Spread:** - **Upper Limit:** 13.0 - **Value:** 10.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 49 - **Group ID:** OG001 - **Value:** 52 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 6.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 77 - **Group ID:** OG001 - **Value:** 79 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 9.0 - **Value:** 7.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 251 - **Group ID:** OG001 - **Value:** 245 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 11.0 - **Value:** 8.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 138 - **Group ID:** OG001 - **Value:** 142 **Units:** Participants #### Outcome Measure 44 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.0 - **Spread:** - **Upper Limit:** 10.0 - **Value:** 9.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 246 - **Group ID:** OG001 - **Value:** 240 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 9.0 - **Value:** 7.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 263 - **Group ID:** OG001 - **Value:** 268 **Units:** Participants #### Outcome Measure 45 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.0 - **Spread:** - **Upper Limit:** 11.0 - **Value:** 9.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 319 - **Group ID:** OG001 - **Value:** 333 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 8.0 - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.0 - **Spread:** - **Upper Limit:** 7.0 - **Value:** 7.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 196 - **Group ID:** OG001 - **Value:** 185 **Units:** Participants ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Time to Recovery **Type:** PRIMARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 2 **Description:** Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Alanine Transaminase (ALT) **Type:** SECONDARY **Unit of Measure:** Units/Liter (U/L) ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 3 **Description:** Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Aspartate Transaminase (AST) **Type:** SECONDARY **Unit of Measure:** Units/Liter (U/L) ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 4 **Description:** Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Creatinine **Type:** SECONDARY **Unit of Measure:** milligrams/deciliter (mg/dL) ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 5 **Description:** Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Glucose **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 6 **Description:** Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Hemoglobin **Type:** SECONDARY **Unit of Measure:** grams/deciliter (g/dL) ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 7 **Description:** Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Platelets **Type:** SECONDARY **Unit of Measure:** 10^9 cells/liter ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 8 **Description:** Blood to evaluate INR was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Prothrombin International Normalized Ratio (INR) **Type:** SECONDARY **Unit of Measure:** ratio ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 9 **Description:** Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Total Bilirubin **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 10 **Description:** Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in White Blood Cell Count (WBC) **Type:** SECONDARY **Unit of Measure:** 10^9 cells/liter ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 11 **Description:** BBlood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Neutrophils **Type:** SECONDARY **Unit of Measure:** 10^9 cells/liter ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 12 **Description:** Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Lymphocytes **Type:** SECONDARY **Unit of Measure:** 10^9 cells/liter ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 13 **Description:** Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Monocytes **Type:** SECONDARY **Unit of Measure:** 10^9 cells/liter ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 14 **Description:** Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Basophils **Type:** SECONDARY **Unit of Measure:** 10^9 cells/liter ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 15 **Description:** Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in Eosinophils **Type:** SECONDARY **Unit of Measure:** 10^9 cells/liter ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 16 **Description:** The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized with data at baseline and at each timepoint. Missing values were imputed using Last Observation Carried Forward. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15, 22, and 29 **Title:** Change in National Early Warning Score (NEWS) From Baseline **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 17 **Description:** Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The safety population includes all participants with available data post baseline, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 18 **Description:** An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The safety population includes all participants with available data post baseline, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Percentage of Participants Reporting Serious Adverse Events (SAEs) **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 19 **Description:** Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Duration of Hospitalization **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 20 **Description:** Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** The analysis population is restricted to randomized participants who were not on non-invasive ventilation or high-flow oxygen at baseline but who subsequently required non-invasive or high-flow oxygen. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Duration of New Non-invasive Ventilation or High Flow Oxygen Use **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 21 **Description:** Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** The analysis population is restricted to randomized participants who were not on oxygen at baseline but who subsequently required oxygen. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Duration of New Oxygen Use **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 22 **Description:** Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** The analysis population is restricted to randomized participants not on a ventilator or ECMO at baseline but who subsequently required a ventilator or ECMO. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 23 **Description:** Duration of oxygen use was measured in days among participants who were on oxygen in based, calculated in two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** The analysis population is restricted to randomized participants who were on oxygen at baseline. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Duration of Oxygen Use **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 24 **Description:** Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses of Remdesivir, or in the 14 doses of Baricitinib/placebo. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 14 **Title:** Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 25 **Description:** The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis population is restricted to randomized participants not on a ventilator or ECMO at baseline. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 26 **Description:** The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis population is restricted to randomized participants not requiring oxygen at baseline. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Percentage of Participants Requiring New Oxygen Use **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 27 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized reporting a clinical score. Missing values were imputed using Last Observation Carried Forward. **Reporting Status:** POSTED **Time Frame:** Day 1, 3, 5, 8, 11, 15, 22, and 29 **Title:** Mean Change in the Ordinal Scale **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 28 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Data was imputed using last observation carried forward or worst possible score based on hospitalization status (2 if not hospitalized, 7 if hospitalized) when there was a change in hospitalization status since last score. Deaths were imputed as an 8. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized. **Reporting Status:** POSTED **Time Frame:** Day 15 **Title:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 29 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 1 **Title:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 30 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 3 **Title:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 31 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 5 **Title:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 32 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 8 **Title:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 33 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 11 **Title:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 34 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 22 **Title:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 35 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 29 **Title:** Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 36 **Description:** The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The ITT population consists of all participants as randomized. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 15 **Title:** 14-day Participant Mortality **Type:** SECONDARY **Unit of Measure:** proportion of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 37 **Description:** The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The ITT population includes all participants as randomized. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** 28-day Participant Mortality **Type:** SECONDARY **Unit of Measure:** proportion of participants ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 38 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The ITT population includes all participants as randomized **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Time to an Improvement of One Category Using an Ordinal Scale **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 39 **Description:** The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The ITT population includes all participants as randomized **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Time to an Improvement of Two Categories Using an Ordinal Scale **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 40 **Description:** The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The ITT population includes participants as randomized, and restricted to those with a baseline NEWS score of 2 or greater. **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 41 **Description:** Blood to evaluate CRP was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in C-reactive Protein (CRP) **Type:** SECONDARY **Unit of Measure:** mg/L ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 42 **Description:** Blood to evaluate d-dimer concentration was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. **Reporting Status:** POSTED **Time Frame:** Days 1, 3, 5, 8, 11, 15 and 29 **Title:** Change From Baseline in D-dimer Concentration **Type:** SECONDARY **Unit of Measure:** mg/L ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 43 **Description:** Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Time to Recovery by Race **Type:** PRIMARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 44 **Description:** Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized and for whom ethnicity was reported **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Time to Recovery by Ethnicity **Type:** PRIMARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo #### Outcome Measure 45 **Description:** Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The intent-to-treat (ITT) population includes all participants who were randomized **Reporting Status:** POSTED **Time Frame:** Day 1 through Day 29 **Title:** Time to Recovery by Sex **Type:** PRIMARY **Unit of Measure:** Days ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG000 **Title:** Remdesivir Plus Baricitinib ##### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. **ID:** OG001 **Title:** Remdesivir Plus Placebo ### Participant Flow Module #### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. Remdesivir: Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide. Baricitinib: Baricitinib is a Janus kinase (JAK) inhibitor with the chemical name \[1-(ethylsulfonyl)-3-(4-(7Hpyrrolo(2,3-d)pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl\]acetonitrile Each tablet contains 2 mg of baricitinib and the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, ferric oxide, lecithin (soya), polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide. **ID:** FG000 **Title:** Remdesivir Plus Baricitinib #### Group **Description:** 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. Remdesivir: Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide. Placebo: The matching Baricitinib placebo contains lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. The coating for the placebo tablet is identical to that of the corresponding active tablet **ID:** FG001 **Title:** Remdesivir Plus Placebo #### Period **Title:** Overall Study ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 23 ###### Reason **Group ID:** FG001 **Number of Subjects:** 36 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 40 ###### Reason **Group ID:** FG001 **Number of Subjects:** 41 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 8 ###### Reason **Group ID:** FG001 **Number of Subjects:** 16 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Became ineligible after enrollment ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Enrolled but treatment not administered ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ###### Reason **Group ID:** FG001 **Number of Subjects:** 9 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Scheduling error ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Transferred to another hospital ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 515 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 518 ##### Milestone **Type:** Treated ###### Achievement **Group ID:** FG000 **Number of Subjects:** 507 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 509 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 431 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 408 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 84 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 110 **Recruitment Details:** Participants were recruited at the participating sites from those admitted with symptoms of COVID-19 confirmed by PCR. Enrollment occurred between 08May2020 and 01Jul2020. **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT03539679 **Brief Title:** HEALTH AND EXERCISE IN THE DEFENSE FORCES **Official Title:** TERVEYS JA LIIKUNTA PUOLUSTUSVOIMISSA #### Organization Study ID Info **ID:** R16189 #### Organization **Class:** OTHER **Full Name:** Tampere University Hospital ### Status Module #### Completion Date **Date:** 2020-07 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2019-09-12 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-11 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-12 **Type:** ESTIMATED #### Start Date **Date:** 2018-05-16 **Type:** ACTUAL **Status Verified Date:** 2019-09 #### Study First Post Date **Date:** 2018-05-29 **Type:** ACTUAL **Study First Submit Date:** 2018-04-25 **Study First Submit QC Date:** 2018-05-16 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Tampere University **Class:** OTHER **Name:** University of Jyvaskyla **Class:** OTHER **Name:** UKK Institute #### Lead Sponsor **Class:** OTHER **Name:** Tampere University Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The most important goal is to create a cost-effective, stimulating model for improving the employee's quality of life, work ability, and job satisfaction in the military operating environment. This is achieved by finding out how to activate an individual with the phone-based gaming and web-based feedback system to improve his physical condition. This study also tries to find out the adequate amount of physical activity to maintain the physical health of workers. Personnel work ability, to work safe in service and effective operation capability of emergency forces require a worker's state of total well-being, in which the health and the physical condition are important parts. The changes in these affects the individual's fitness to military. This study develops a model to encourage an individual to carry out physical activity by himself. This will lead to reduce the sick leaves and improve the health and fitness. Physical activity reduces morbidity. Professional soldiers must maintain their physical condition and skills. The study explores the optimum amount of working-age physical activity. It helps to maintain the working ability and one's fitness to field operations. With the help of the developed model it is possible cost-effectively activate a large number of employees to move more and to live more healthily. **Detailed Description:** In this study it will be used motion sensors which are sending feedback to individuals mobile phone. Feedback is also given by email and in an interview after analyzing data from cloud service. In the beginning of the study it will analyzed blood test, salivary test, body composition, height weight and basic motion. All volunteers are also answering a questionnaire. There will be an intervention group and a control group. The intervention group will receive feedback during the all six months they are carrying the motion sensor. After 6 and 12 months the basic analyzes will be repeated. Sick leaves and the changes in the muscular fitness test and changes in the 12-minutes running test will be analyzed. ### Conditions Module **Conditions:** - Physical Condition, Minor Psychological Component **Keywords:** - Exercise, sickness absences, health, military fitness ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Intervention group and control group. ##### Masking Info **Masking:** SINGLE **Masking Description:** Exclusion criteria is that a volunteer must be health enough to have permission to take part in the military fitness tests. **Who Masked:** - PARTICIPANT **Primary Purpose:** OTHER #### Enrollment Info **Count:** 500 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Encouraging physical activity by using motion sensor and feedback. **Intervention Names:** - Other: Encouraging physical activity. **Label:** Encouraging physical activity **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No intervention. **Label:** CONTROL GROUP **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Encouraging physical activity **Description:** Encouraging physical activity with motion sensor's feedback. **Name:** Encouraging physical activity. **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** 12-minutes running test are measured. **Measure:** Better physical condition. **Time Frame:** 12 months. **Description:** Muscular fitness test. **Measure:** Better physical condition. **Time Frame:** 12 months. **Description:** Number of participants with better outcome in health habits (sleeping, eating, exercise). **Measure:** Positive changes in the TELI v 1.0 questionnaire. **Time Frame:** 12 months. #### Primary Outcomes **Description:** 12-minutes running test are measured. **Measure:** Better physical condition. **Time Frame:** 6 months. **Description:** The amount of sick leaves are measured. **Measure:** Less sick leaves. **Time Frame:** From past 12 months up to next 12 months. #### Secondary Outcomes **Description:** Number of participants with better outcome in health habits (sleeping, eating, exercise). **Measure:** Positive changes in the TELI v 1.0 questionnaire. **Time Frame:** 6 months. **Description:** Muscular fitness test. **Measure:** Better physical condition. **Time Frame:** 6 months. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Voluntaries armed forces workers. Exclusion Criteria: * Health enough to participate the military fitness test. **Healthy Volunteers:** True **Maximum Age:** 60 Years **Minimum Age:** 19 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** KAI I PARKKOLA, PROF EMER **Phone:** +358 40 5003116 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** HEIKKI KYRÖLÄINEN, PROF **Phone:** +358 40 5408703 **Role:** CONTACT #### Locations **Location 1:** **City:** Tampere **Contacts:** ***Contact 1:*** - **Name:** EMILIA PIETILÄINEN, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Finland **Facility:** Kai Parkkola **Status:** RECRUITING **Zip:** 33014 #### Overall Officials **Official 1:** **Affiliation:** PROF EMER, UNIVERSITY OF TAMPERE **Name:** KAI I PARKKOLA, PROF EMER **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** PROF, UNIVERSITY OF JYVÄSKYLÄ **Name:** HEIKKI KYRÖLÄINEN, PROF **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01275079 **Brief Title:** Change of Nasalance After Tonsillectomy in Thai Adult **Official Title:** Change of Nasalance After Tonsillectomy in Thai Adult #### Organization Study ID Info **ID:** Resident_Permpoon #### Organization **Class:** OTHER **Full Name:** Chulalongkorn University ### Status Module #### Completion Date **Date:** 2011-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2011-01-12 **Type:** ESTIMATED **Last Update Submit Date:** 2011-01-11 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2011-10 **Type:** ESTIMATED #### Start Date **Date:** 2011-01 **Status Verified Date:** 2011-01 #### Study First Post Date **Date:** 2011-01-12 **Type:** ESTIMATED **Study First Submit Date:** 2010-11-26 **Study First Submit QC Date:** 2011-01-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Chulalongkorn University #### Responsible Party **Old Name Title:** Permpoon Piyaman **Old Organization:** Department of Otolaryngology , Faculty of Medicine , Chulalongkorn University ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to analyze the change of nasalance after tonsillectomy in Thai adults. ### Conditions Module **Conditions:** - Voice Quality - Tonsillectomy **Keywords:** - tonsillectomy - nasalance - tonsil volume - Thai - adult ### Design Module #### Bio Spec **Description:** Rt. and Lt.tonsil **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Thai adults age over 18 years who were perform bilateral tonsillectomy * The pathological are not malignancy Exclusion Criteria: * Craniofacial anomalies * Neurological problems * History of Peritonsillar abscess * Performed other operation beside tonsillectomy * Can't read Thais * Visual problem that effect reading * Nasal disease that cause nasal obstruction **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Thai adults who were performed tonsillectomy ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Permpoon Piyaman, MD **Phone:** +6622564103 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Napadon Tangjaturonrasme, ENT **Phone:** +6622564103 **Role:** CONTACT #### Locations **Location 1:** **City:** Bangkok **Contacts:** ***Contact 1:*** - **Name:** Permpoon Piyaman, MD - **Role:** CONTACT ***Contact 2:*** - **Name:** Napadon Tangjaturonrasme - **Role:** CONTACT **Country:** Thailand **Facility:** Department of otolaryngology, faculty of medicine, Chulalongkorn university **Status:** RECRUITING **Zip:** 10330 #### Overall Officials **Official 1:** **Affiliation:** Department of otolaryngology, faculty of medicine, Chulalongkorn university **Name:** Permpoon Piyaman, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05123079 **Brief Title:** Relative Bioavailability and Food Effect Following Single Oral Dose of Darigabat Tablet Formulations in Healthy Participants **Official Title:** A Randomized, 3-Period Crossover Trial to Evaluate the Relative Bioavailability and Food Effect Following Single Oral Dose of Darigabat Tablet Formulations in Healthy Adult Participants #### Organization Study ID Info **ID:** CVL-865-1002 #### Organization **Class:** INDUSTRY **Full Name:** Cerevel Therapeutics, LLC ### Status Module #### Completion Date **Date:** 2021-12-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-01-21 **Type:** ACTUAL **Last Update Submit Date:** 2022-01-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-11-21 **Type:** ACTUAL #### Start Date **Date:** 2021-11-02 **Type:** ACTUAL **Status Verified Date:** 2022-01 #### Study First Post Date **Date:** 2021-11-17 **Type:** ACTUAL **Study First Submit Date:** 2021-11-05 **Study First Submit QC Date:** 2021-11-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Cerevel Therapeutics, LLC #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a Phase 1, single-center trial in healthy participants. This is a crossover design, open-label treatment trial with 3 periods, 6 sequences. **Detailed Description:** The trial is an open-label, randomized, 3-period, 6-sequence, crossover design to investigate the relative bioavailability and effect of food on Darigabat. ### Conditions Module **Conditions:** - Healthy **Keywords:** - Healthy Volunteer - Bioavailability - Food effect ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** This is a Phase 1, single-center trial in healthy participants. The trial is an open-label, randomized, 3-period, 6-sequence, crossover design to investigate the relative bioavailability and effect of food of Darigabat from a single oral. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Oral Dose **Intervention Names:** - Drug: Darigabat **Label:** Single Oral Dose of 25 mg administered as 1 x 25 mg tablet, Fasted (Without Food) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Oral Dose **Intervention Names:** - Drug: Darigabat **Label:** Single Oral Dose of 25 mg administered as 1 x 25 mg tablet, Fed (With food) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Oral Dose **Intervention Names:** - Drug: Darigabat **Label:** Single Oral Dose of 25 mg administered as 2 x 7.5 and 2 x 5.0 mg tablets, Fasted (Without Food) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Single Oral Dose of 25 mg administered as 1 x 25 mg tablet, Fasted (Without Food) - Single Oral Dose of 25 mg administered as 1 x 25 mg tablet, Fed (With food) - Single Oral Dose of 25 mg administered as 2 x 7.5 and 2 x 5.0 mg tablets, Fasted (Without Food) **Description:** Tablets **Name:** Darigabat **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Peak Plasma Concentration (Cmax) for Darigabat under fasted conditions **Measure:** Single Dose: Peak Plasma Concentrations **Time Frame:** Day 1 to Day 4 **Description:** Area under the plasma concentration-time curve (AUC) for Darigabat under fasted conditions **Measure:** Single Dose: Area under the plasma concentration-time curve **Time Frame:** Day 1 to Day 4 **Description:** Area under the plasma concentration-time curve from time zero to last concentration measured (AUClast) for Darigabat under fasted conditions **Measure:** Single Dose: Area under the plasma concentration-time curve from time zero to last concentration measured **Time Frame:** Day 1 to Day 4 **Description:** Time of Maximum Observed Plasma Concentrations (Tmax) for Darigabat under fasted conditions **Measure:** Single Dose: Time of Maximum Observed Plasma Concentrations **Time Frame:** Day 1 to Day 4 **Description:** Peak Plasma Concentration (Cmax) for Darigabat under fed and fasted conditions **Measure:** Secondary Objective: Single Dose: Peak Plasma Concentrations **Time Frame:** Day 1 to Day 4 **Description:** Area under the plasma concentration-time curve (AUC) for Darigabat under fed and fasted conditions **Measure:** Secondary Objective: Single Dose: Area under the plasma concentration-time curve **Time Frame:** Day 1 to Day 4 **Description:** Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-865 under fed and fasted conditions **Measure:** Secondary Objective: Single Dose: Area under the plasma concentration-time curve from time zero to infinity **Time Frame:** Day 1 to Day 4 **Description:** Time of Maximum Observed Plasma Concentrations (Tmax) for Darigabat under fasted and fed conditions **Measure:** Secondary Objective: Single Dose: Time of Maximum Observed Plasma Concentrations **Time Frame:** Day 1 to Day 4 #### Secondary Outcomes **Description:** Number of subjects with reported Treatment Emergent Adverse Events (TEAEs) **Measure:** Secondary Outcome (AE) **Time Frame:** Day 1 to Day 4 **Description:** Number of subjects with clinically significant changes in Electrocardiograms. **Measure:** Secondary Outcome (ECGs) **Time Frame:** Day 1 to Day 4 **Description:** Number of subjects with clinically significant changes in laboratory measures. **Measure:** Secondary Outcome (Labs) **Time Frame:** Day 1 to Day 4 **Description:** Number of subjects with clinically meaningful changes in vitals signs. **Measure:** Secondary Outcome (Vital Signs) **Time Frame:** Day 1 to Day 4 **Description:** Number of subjects with clinically significant changes in physical and neurological exams. **Measure:** Secondary Outcome (Physical/Neurological Exam) **Time Frame:** Day 1 to Day 4 **Description:** Changes from baseline of the Columbia-Suicide Severity Rating Scale (C-SSRS). The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent). **Measure:** Secondary Outcome (C-SSRS) **Time Frame:** Day 1 to Day 4 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Women of nonchildbearing potential and men, ages 18 to 55 years, inclusive. 2. Healthy as determined by medical evaluation by the investigator. 3. Body mass index of 18.5 to 30.0 kg/m2, inclusive, and a total body weight \>50 kg (110 lbs). 4. A male participant with a pregnant or a nonpregnant partner of childbearing potential must agree to use contraception. 5. Capable of giving signed informed consent and complying with study requirements. Exclusion Criteria: 1. Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus), malignancy (except for basal cell carcinoma of the skin and cervical carcinoma in situ, at the discretion of the investigator), hematological, immunological, neurological, or psychiatric disease. 2. Serious risk of suicide in the opinion of the investigator. 3. History of substance or alcohol-use disorder (excluding nicotine or caffeine) within 12 months prior to signing the ICF. 4. Any condition that could possibly affect drug absorption. 5. Receipt of SARS-CoV2 vaccine or booster as follows: * mRNA: within 14 days prior to dosing * Non-mRNA: within 28 days prior to dosing 6. Have recently been diagnosed with symptomatic COVID-19 or test positive for COVID-19 within 30 days prior to signing the ICF. 7. Taking any prohibited medication prior to randomization or likely to require prohibited concomitant therapy. 8. History of HIV, hepatitis B, or hepatitis C infection, or positive result for HIV, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody. 9. Positive drug screen (including nicotine and cannabinoids) or a positive test for alcohol. 10. Abnormal clinical laboratory test results or vital measurements at Screening. 11. Any other abnormal safety findings unless, based on the investigator's judgment, the findings are not medically significant and would not impact the safety of the participant or the interpretation of the trial results. **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tempe **Country:** United States **Facility:** Celerion Inc. **State:** Arizona **Zip:** 85283 #### Overall Officials **Official 1:** **Affiliation:** Cerevel Therapeutics, LLC **Name:** Ann M Dandurand, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT03072979 **Brief Title:** A Study to Quantify Tumour Perfusion for Spine Metastasis Treated With Stereotactic Body Radiotherapy (SBRT) **Official Title:** Reduction in Tumour Perfusion for Spine Metastasis Treated With Stereotactic Body Radiotherapy (SBRT) #### Organization Study ID Info **ID:** 2016/01179 #### Organization **Class:** OTHER **Full Name:** National University Hospital, Singapore ### Status Module #### Completion Date **Date:** 2018-12-31 #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2017-03-08 **Type:** ACTUAL **Last Update Submit Date:** 2017-03-02 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2017-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2017-01-21 **Type:** ACTUAL **Status Verified Date:** 2017-03 #### Study First Post Date **Date:** 2017-03-08 **Type:** ACTUAL **Study First Submit Date:** 2017-02-28 **Study First Submit QC Date:** 2017-03-02 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** National University of Singapore #### Lead Sponsor **Class:** OTHER **Name:** National University Hospital, Singapore #### Responsible Party **Investigator Affiliation:** National University Hospital, Singapore **Investigator Full Name:** Radiation Oncology **Investigator Title:** Dr Balamurugan Vellayappan **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Pre-clinical evidence suggests that radiotherapy reduces tumour-associated vasculature. The investigators will conduct a single-arm prospective study to quantify the reduction in tumour vasculature post-radiotherapy ### Conditions Module **Conditions:** - Spine Metastasis ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 18 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Stereotactic body radiotherapy **Name:** Stereotactic body radiotherapy **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Description:** Reduction in vasculature measured by changes on Dynamic Contrast enhanced MRI **Measure:** Reduction in vasculature **Time Frame:** 3 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age ≥21 years of age * Proven metastatic disease, excluding haematological and germ cell neoplasms * Life expectancy \>3 months, Eastern Cooperative Oncology group (ECOG) 0-2 Exclusion Criteria: * The patient must not have an allergy to gadolinium contrast that will limit the ability to image the tumour by MRI safely even with the use of premedication * eGFR \< 30 mL/min or if patient is suffering from acute renal insufficiency * Prior radiotherapy to the specified region * Recent surgery to affected spinal levels, or patients requiring immediate surgical intervention * Spinal instability score (SINS) \>12 * Symptomatic cord compression (Bilksy grade 2 or 3), or worsening neurological deficits * Body weight of more than 120kg * Pregnancy **Minimum Age:** 21 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** A total of 18 patients from National University Hospital (NUH) will be enrolled. Informed consent will be taken from patients prior to trial entry at NUH. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** BALAMURUGAN VELLAYAPPAN, MBBS, FRANZCR **Phone:** 67795555 **Role:** CONTACT #### Locations **Location 1:** **City:** Singapore **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** BALAMURUGAN VELLAYAPPAN - **Role:** CONTACT **Country:** Singapore **Facility:** National University Hospital **Status:** RECRUITING ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009385 - Term: Neoplastic Processes - ID: D000009369 - Term: Neoplasms - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Metastases - ID: M12330 - Name: Neoplastic Processes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009362 - Term: Neoplasm Metastasis ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05019079 **Brief Title:** Protective Effect of Electroacupuncture on Lung in Patients Undergoing General Anesthesia **Official Title:** Protective Effect of Electroacupuncture on Lung in Patients Undergoing General Anesthesia #### Organization Study ID Info **ID:** LDing #### Organization **Class:** OTHER **Full Name:** Beijing Hospital of Traditional Chinese Medicine ### Status Module #### Completion Date **Date:** 2023-09-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2021-08-24 **Type:** ACTUAL **Last Update Submit Date:** 2021-08-20 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2021-09-01 **Type:** ESTIMATED **Status Verified Date:** 2021-08 #### Study First Post Date **Date:** 2021-08-24 **Type:** ACTUAL **Study First Submit Date:** 2021-07-25 **Study First Submit QC Date:** 2021-08-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Lingling Ding #### Responsible Party **Investigator Affiliation:** Beijing Hospital of Traditional Chinese Medicine **Investigator Full Name:** Lingling Ding **Investigator Title:** Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Objective to investigate the protective effect of preoperative electroacupuncture on lung function in patients with mechanical ventilation for more than 2 hours under general anesthesia **Detailed Description:** Randomized parallel control study. From September 1, 2021 to December 31, 2022, patients with mechanical ventilation time more than 2 hours will be randomly divided into electroacupuncture pretreatment group and blank control group. The blood gas index, ventilator parameters and serum inflammatory factor concentration of patients will be evaluated to evaluate whether electroacupuncture has protective effect on lung function of patients with mechanical ventilation. ### Conditions Module **Conditions:** - Electroacupuncture - Lung Injury, Ventilator Induced **Keywords:** - Electroacupuncture - Lung protection - ventilator induced lung injury ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 72 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In the electroacupuncture group, acupoints of Lieque (+), Chize (-), Sanyinjiao (-), Zusanli (+), Tanzhong (+) and Yutang (-) will be selected for electrical stimulation. Density wave will be selected, and the current intensity should be tolerated by the patients. Conventional anesthesia operation could be started after the connection of electroacupuncture, and acupuncture point stimulation was stopped 30min later. **Intervention Names:** - Other: electroacupuncture **Label:** electroacupuncture group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The patient underwent routine anesthesia without acupuncture treatment **Label:** control group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - electroacupuncture group **Description:** In the electroacupuncture group, acupoints of Lieque (+), Chize (-), Sanyinjiao (-), Zusanli (+), Tanzhong (+) and Yutang (-) will be selected for electrical stimulation. Density wave will be selected, and the current intensity should be tolerated by the patients. Conventional anesthesia operation could be started after the connection of electroacupuncture, and acupuncture point stimulation will be stopped 30min later. **Name:** electroacupuncture **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** record oxygenation index **Measure:** oxygenation index **Time Frame:** Before anesthesia **Description:** record oxygenation index **Measure:** oxygenation index **Time Frame:** 2 hours after tracheal intubation **Description:** record oxygenation index **Measure:** oxygenation index **Time Frame:** 5 minutes after tracheal intubation removal #### Secondary Outcomes **Description:** Assess the quality of recovery during recovery **Measure:** Postoperative comfort score **Time Frame:** during anesthesia recovery period **Description:** Assess the quality of recovery during recovery **Measure:** sedation score (Ramsay) **Time Frame:** during anesthesia recovery period **Description:** Assess the quality of recovery during recovery **Measure:** restfulness score (DRS) **Time Frame:** during anesthesia recovery period **Description:** Assess the quality of recovery during recovery **Measure:** visual analogue scale (VAS) **Time Frame:** during anesthesia recovery period **Description:** Assess the quality of postoperative recovery **Measure:** Length of stay **Time Frame:** 1 week after discharge, the patient's length of stay will be recorded through medical record system **Description:** Assess the quality of postoperative recovery **Measure:** postoperative time in hospital **Time Frame:** 1 week after discharge, the patient's postoperative time in hospital will be recorded through medical record system **Description:** Assess the quality of postoperative recovery **Measure:** postoperative complications of major organs **Time Frame:** Major organ complications during hospitalization，assessed up to 30 days after surgery **Description:** Assess the quality of postoperative recovery **Measure:** mortality within 30 days **Time Frame:** mortality within 30 days will be recorded **Description:** The perioperative inflammation level will be assessed **Measure:** Expression of IL-18 in serum **Time Frame:** Before anesthetic induction the radial artery blood samples will be collected, and the expressions of IL-18 in serum will be detected by flow cytometry **Description:** The perioperative inflammation level will be assessed **Measure:** Expression of IL-18 in serum **Time Frame:** 5minutes after tracheal intubation removal the radial artery blood samples will be collected, and the expressions of IL-18 in serum will be detected by flow cytometry **Description:** The perioperative inflammation level will be assessed **Measure:** Expression of IL-1β in serum **Time Frame:** Before anesthetic induction the radial artery blood samples will be collected, and the expressions of IL-1β in serum will be detected by flow cytometry **Description:** The perioperative inflammation level will be assessed **Measure:** Expression of IL-1β in serum **Time Frame:** 5minutes after tracheal intubation removal the radial artery blood samples will be collected, and the expressions of IL-1β in serum will be detected by flow cytometry **Description:** The perioperative inflammation level will be assessed **Measure:** Expression of IL-10 in serum **Time Frame:** Before anesthetic induction the radial artery blood samples will be collected, and the expressions of IL-10 in serum will be detected by flow cytometry **Description:** The perioperative inflammation level will be assessed **Measure:** Expression of IL-10 in serum **Time Frame:** 5minutes after tracheal intubation removal the radial artery blood samples will be collected, and the expressions of IL-10 in serum will be detected by flow cytometry **Description:** Intraoperative vital signs will be recorded **Measure:** Mean arterial pressure **Time Frame:** Before anesthesia ,2 hours after tracheal intubation , and 5minutes after tracheal intubation removal **Description:** Intraoperative vital signs will be recorded **Measure:** heart rate **Time Frame:** Before anesthesia , 2 hours after tracheal intubation , and 5minutes after tracheal intubation removal **Description:** Intraoperative vital signs will be recorded **Measure:** BIS **Time Frame:** Before anesthesia , 2 hours after tracheal intubation , and 5minutes after tracheal intubation removal **Description:** Intraoperative vital signs will be recorded **Measure:** extubation time **Time Frame:** Before anesthesia , 2 hours after tracheal intubation , and 5minutes after tracheal intubation removal **Description:** Intraoperative vital signs will be recorded **Measure:** anesthesia dosage **Time Frame:** Before anesthesia , 2 hours after tracheal intubation , and 5minutes after tracheal intubation removal ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients undergoing general anesthesia in our hospital; * Ages 18-60; * American Society of Anesthesiologists (ASA) grade ⅱ \~ III , no severe respiratory, circulation, liver, kidney, coagulation function abnormalities; * Expected duration of operation \>2h; * Surgical grade 2-4; * No serious lung infection and lung disease; * Body mass index (BMI) 18\~30 kg/m2; There are no contraindications for electroacupuncture stimulation. Exclusion Criteria: * Patients with severe circulatory or other system dysfunction; * Patients with pulmonary and one-lung ventilation; * Unwilling to cooperate with the patient; * Patients with low compliance. **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Lingling Ding, Doctor **Phone:** +86 010 52176647 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Jiaqi Ning, bachelor **Phone:** +86 010 52176647 **Role:** CONTACT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000013898 - Term: Thoracic Injuries - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M28143 - Name: Lung Injury - Relevance: HIGH - As Found: Lung Injury - ID: M28152 - Name: Ventilator-Induced Lung Injury - Relevance: HIGH - As Found: Lung Injury, Ventilator Induced - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M16657 - Name: Thoracic Injuries - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000055370 - Term: Lung Injury - ID: D000055397 - Term: Ventilator-Induced Lung Injury ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01904279 **Acronym:** JIGSAW 117 **Brief Title:** A Study of Subcutaneously (SC) Administered Tocilizumab (TCZ) in Participants With Polyarticular-Course Juvenile Idiopathic Arthritis (pJIA) **Official Title:** A Phase Ib, Open-Label, Multicenter Study to Investigate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab Following Subcutaneous Administration to Patients With Polyarticular Juvenile Idiopathic Arthritis #### Organization Study ID Info **ID:** WA28117 #### Organization **Class:** INDUSTRY **Full Name:** Hoffmann-La Roche #### Secondary ID Infos **ID:** 2012-003486-18 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2016-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-06-14 **Type:** ACTUAL **Last Update Submit Date:** 2017-05-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-05 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-03-16 **Type:** ACTUAL **Results First Submit Date:** 2017-01-24 **Results First Submit QC Date:** 2017-01-24 #### Start Date **Date:** 2013-07 **Status Verified Date:** 2017-05 #### Study First Post Date **Date:** 2013-07-22 **Type:** ESTIMATED **Study First Submit Date:** 2013-06-14 **Study First Submit QC Date:** 2013-07-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hoffmann-La Roche #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This open-label, multicenter study evaluated the pharmacokinetics, pharmacodynamics and safety of SC administered TCZ in participants with pJIA. ### Conditions Module **Conditions:** - Juvenile Idiopathic Arthritis ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 52 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants with body weight less than (\<) 30 kilograms (kg) will be administered 162 milligrams (mg) of TCZ as a SC injection every 3 weeks (Q3W) for 52 weeks. **Intervention Names:** - Drug: Tocilizumab **Label:** TCZ SC 162 mg Q3W **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants with body weight greater than or equal to (\>/=) 30 kg will be administered 162 mg of TCZ as a SC injection every 2 weeks (Q2W) for 52 weeks. **Intervention Names:** - Drug: Tocilizumab **Label:** TCZ SC 162 mg Q2W **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - TCZ SC 162 mg Q2W - TCZ SC 162 mg Q3W **Description:** Participants will receive 162 mg of TCZ as SC injection Q3W or Q2W for 52 weeks **Name:** Tocilizumab **Other Names:** - RoActemra/Actemra **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016, 2022, 2064, 2112, 2160, 2520 hours post Day 1 dose (additionally at 6, 12, 48, 120, 2028 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016, 2022, 2028, 2040, 2064, 2112, 2160, 2520 hours post Day 1 dose. **Measure:** Minimum Serum Concentration (Cmin) of TCZ at Steady State **Time Frame:** Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section) **Description:** Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016 hours post Day 1 dose (additionally at 6, 12, 48, 120 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016 post Day 1 dose. **Measure:** Area Under the Curve at Steady-state Over a 12-week Interval (AUC12weeks) of TCZ Treatment **Time Frame:** Pre-dose (Hour 0) up to 2016 hours post Day 1 dose (detailed timeframe is provided in outcome description section) **Description:** Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016, 2022, 2064, 2112, ,2160, 2520 hours post Day 1 dose (additionally at 6, 12, 48, 120, 2028 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016, 2022, 2028, 2040, 2064, 2112, 2160, 2520 hours post Day 1 dose. **Measure:** Maximum Serum Concentration (Cmax) of TCZ at Steady State **Time Frame:** Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section) #### Secondary Outcomes **Description:** IL-6 is a cytokine associated with disease activity in juvenile idiopathic arthritis (JIA) including the polyarticular juvenile idiopathic arthritis (pJIA) subset. It is found in high levels in the synovial fluid and is associated with indicators of inflammatory activity. **Measure:** Change From Baseline in Serum Interleukin-6 (IL-6) Levels **Time Frame:** Baseline, Days 0.25, 0.5, 2, 4, 5, 84.25, 84.5, 85, 86, 88, 90; Weeks 2, 3, 4, 6, 12, 14, 15, 27, 28, 36, 44, 52 **Measure:** Change From Baseline in Soluble IL-6 Receptor Levels **Time Frame:** Baseline, Days 0.25, 0.5, 2, 4, 5, 84.25, 84.5, 85, 86, 88, 90; Weeks 2, 3, 4, 6, 12, 14, 15, 27, 28, 36, 44, 52 **Measure:** Change From Baseline in C-Reactive Protein (CRP) Levels **Time Frame:** Baseline, Weeks 4, 6, 9, 12,18, 20, 27, 28, 36, 44, 45, 51, 52 **Description:** The ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline indicates improvement. **Measure:** Change From Baseline in Erythrocyte Sedimentation Rate (ESR) **Time Frame:** Baseline, Week 4, 6, 9, 12, 18, 20, 27, 28, 36, 44, 45, 51, 52 **Measure:** Percentage of Participants With Anti-TCZ Antibodies of Neutralizing Potential **Time Frame:** Baseline up to Week 52 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Ages 1 year (12 years for participants in Russia) up to and including 17 years at screening * Diagnosis of pJIA according to International League of Associations for Rheumatology classification * Rheumatoid factor (RF)-positive pJIA * RF-negative pJIA * Extended oligoarticular JIA with a polyarticular course * History of inadequate clinical response (in the opinion of the treating physician) to or inability to tolerate methotrexate (MTX) * Participants currently receiving TCZ by the intravenous (IV) route of administration and with well-controlled disease do not require a period of discontinuation of IV TCZ and should have their first dose of SC TCZ administered on the date that their next IV TCZ infusion would be due. Participants participating in the study may be either naive to TCZ therapy or may be switching from IV to SC. The total number of participants switching from IV TCZ must account for no more than 50 percent (%) of the total participant number. To account for the baseline TCZ concentrations in these participants, information on the last 4 IV TCZ infusions prior to baseline will be collected * Concurrent treatment with disease-modifying antirheumatic drugs (DMARDs) (including MTX), nonsteroidal anti-inflammatory drugs (NSAIDs), and oral corticosteroids are permitted at the discretion of the investigator * Females of childbearing potential and non-sterile males with female partner of childbearing potential must agree to use effective contraception as defined by protocol Exclusion Criteria: * Prior discontinuation of IV TCZ because of inadequate clinical response or safety events (including hypersensitivity) * Participants with poorly controlled disease (in the opinion of the treating physician) despite current treatment with IV TCZ * pJIA that is well controlled by any treatment agent other than TCZ (Juvenile Arthritis Disease Activity Score 71 \[JADAS-71\] less than or equal to (\< / =) 3.8) * Participants who are wheelchair-bound or bedridden * Any other auto-immune, rheumatic disease, or overlapping syndrome other than the permitted pcJIA subsets * Lack of recovery from recent surgery or an interval of \<6 weeks since surgery at the time of the screening visit * Females who are pregnant, lactating, or intending to become pregnant during study conduct * Any significant concurrent medical or surgical condition that would jeopardize the participant's safety or ability to complete the study * Known human immunodeficiency virus (HIV) infection or other acquired forms of immune compromise or inborn conditions characterized by a compromised immune system * History of alcohol, drug, or chemical abuse within 6 months of screening * Any active acute, subacute, chronic, or recurrent bacterial, viral, or systemic fungal infection or any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completed within 4 weeks of the screening visit or oral antibiotics completed within 2 weeks of the screening visit * History of atypical tuberculosis (TB) or active TB requiring treatment within 2 years prior to screening visit * Positive purified protein derivative (PPD) at screen, unless treated with anti-TB therapy for at least 4 weeks prior to receiving study drug and chest radiograph is negative for active TB within 6 months of screening visit according to local practice * History of reactivation or new onset of a systemic infection such as herpes zoster or Epstein-Barr virus within 2 months of the screening visit * Hepatitis B surface antigen or hepatitis C antibody positivity or chronic viral or autoimmune hepatitis * History of concurrent serious gastrointestinal disorders such as ulcer or inflammatory bowel disease, Crohn's disease, ulcerative colitis, or other symptomatic lower gastrointestinal conditions * History of or current cancer or lymphoma * Uncontrolled diabetes mellitus with elevated glycosylated hemoglobin * Active uveitis at screening * Inadequate hematologic, renal or liver function * Prior stem cell transplant at any time **Maximum Age:** 17 Years **Minimum Age:** 1 Year **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Hartford **Country:** United States **State:** Connecticut **Zip:** 06106 **Location 2:** **City:** Chicago **Country:** United States **State:** Illinois **Zip:** 60611 **Location 3:** **City:** Chicago **Country:** United States **State:** Illinois **Zip:** 60637 **Location 4:** **City:** Hackensack **Country:** United States **State:** New Jersey **Zip:** 07601 **Location 5:** **City:** Charlotte **Country:** United States **State:** North Carolina **Zip:** 28203 **Location 6:** **City:** Durham **Country:** United States **State:** North Carolina **Zip:** 27710 **Location 7:** **City:** Cincinnati **Country:** United States **State:** Ohio **Zip:** 45229-3039 **Location 8:** **City:** Tulsa **Country:** United States **State:** Oklahoma **Zip:** 74135 **Location 9:** **City:** Salt Lake City **Country:** United States **State:** Utah **Zip:** 84109 **Location 10:** **City:** Seattle **Country:** United States **State:** Washington **Zip:** 98105 **Location 11:** **City:** Buenos Aires **Country:** Argentina **Zip:** 1270 **Location 12:** **City:** Westmead **Country:** Australia **State:** New South Wales **Zip:** 2145 **Location 13:** **City:** Parkville **Country:** Australia **State:** Victoria **Zip:** 3052 **Location 14:** **City:** Rio de Janeiro **Country:** Brazil **State:** RJ **Zip:** 20551-030 **Location 15:** **City:** Rio de Janeiro **Country:** Brazil **State:** RJ **Zip:** 21941-912 **Location 16:** **City:** Sao Paulo **Country:** Brazil **State:** SP **Zip:** 05403-000 **Location 17:** **City:** Sao Paulo **Country:** Brazil **State:** SP **Zip:** 22793-080 **Location 18:** **City:** Calgary **Country:** Canada **State:** Alberta **Zip:** T3B 6A8 **Location 19:** **City:** Ottawa **Country:** Canada **State:** Ontario **Zip:** K1H 8L1 **Location 20:** **City:** Toronto **Country:** Canada **State:** Ontario **Zip:** M5G 1X8 **Location 21:** **City:** Le Kremlin Bicêtre **Country:** France **Zip:** 94275 **Location 22:** **City:** Berlin **Country:** Germany **Zip:** 13353 **Location 23:** **City:** Freiburg **Country:** Germany **Zip:** 79106 **Location 24:** **City:** Sankt Augustin **Country:** Germany **Zip:** 53757 **Location 25:** **City:** Roma **Country:** Italy **State:** Lazio **Zip:** 00165 **Location 26:** **City:** Genova **Country:** Italy **State:** Liguria **Zip:** 16147 **Location 27:** **City:** Firenze **Country:** Italy **State:** Toscana **Zip:** 50139 **Location 28:** **City:** Monterrey **Country:** Mexico **Zip:** 64460 **Location 29:** **City:** Moscow **Country:** Russian Federation **Zip:** 115522 **Location 30:** **City:** Moscow **Country:** Russian Federation **Zip:** 119991 **Location 31:** **City:** Esplugas de Llobregat **Country:** Spain **State:** Barcelona **Zip:** 08950 **Location 32:** **City:** Madrid **Country:** Spain **Zip:** 28034 **Location 33:** **City:** Madrid **Country:** Spain **Zip:** 28046 **Location 34:** **City:** Bristol **Country:** United Kingdom **Zip:** BS2 8BJ **Location 35:** **City:** Liverpool **Country:** United Kingdom **Zip:** L12 2AP #### Overall Officials **Official 1:** **Affiliation:** Hoffmann-La Roche **Name:** Clinical Trials **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Ruperto N, Brunner HI, Ramanan AV, Horneff G, Cuttica R, Henrickson M, Anton J, Boteanu AL, Penades IC, Minden K, Schmeling H, Hufnagel M, Weiss JE, Pardeo M, Nanda K, Roth J, Rubio-Perez N, Hsu JC, Wimalasundera S, Wells C, Bharucha K, Douglass W, Bao M, Mallalieu NL, Martini A, Lovell D, Benedetti F; Paediatric Rheumatology INternational Trials Organisation (PRINTO) and the Paediatric Rheumatology Collaborative Study Group (PRCSG). Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis. Rheumatology (Oxford). 2021 Oct 2;60(10):4568-4580. doi: 10.1093/rheumatology/keab047. **PMID:** 33506875 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases - ID: D000003240 - Term: Connective Tissue Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M4476 - Name: Arthritis - Relevance: HIGH - As Found: Arthritis - ID: M4479 - Name: Arthritis, Juvenile - Relevance: HIGH - As Found: Juvenile Idiopathic Arthritis - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001168 - Term: Arthritis - ID: D000001171 - Term: Arthritis, Juvenile ### Misc Info Module #### Removed Countries - Country: Peru - Country: Poland - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Safety population #### Event Groups **Group ID:** EG000 **Title:** TCZ SC 162 mg Q3W **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** EG000 **Other Num Affected:** 23 **Other Num at Risk:** 27 **Serious Number Affected:** 1 **Serious Number At Risk:** 27 **Title:** TCZ SC 162 mg Q3W **Group ID:** EG001 **Title:** TCZ SC 162 mg Q2W **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. **ID:** EG001 **Other Num Affected:** 22 **Other Num at Risk:** 25 **Serious Number Affected:** 2 **Serious Number At Risk:** 25 **Title:** TCZ SC 162 mg Q2W **Frequency Threshold:** 5 #### Other Events **Term:** Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Ear Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Abdominal Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Aphthous Ulcer **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Diarrhoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection Site Erythema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection Site Haematoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection Site Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection Site Pruritus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection Site Swelling **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Vessel Puncture Site Haematoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Bronchitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Ear Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Gastroenteritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Impetigo **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Influenza **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Nasophryngitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Otitis Media **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Paronychia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Rhinitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Upper Respiratory Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Viral Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Alanine Aminotransferase Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (19.0) **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Back Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Joint Swelling **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Juvenile Idiopathic Arthritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Neck Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Pain in extremity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Skin Papilloma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (19.0) **Term:** Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Insomnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Epistaxis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Oropharyngeal Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Alopecia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Dermatitis Atopic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Eczema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Haematoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (19.0) #### Serious Events **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 27 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 25 **Term:** Decreased appetite **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (19.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 27 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 25 **Term:** Croup infectious **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 27 **Group ID:** EG001 **Num At Risk:** 25 **Term:** Varicella **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 27 **Group ID:** EG001 **Num At Risk:** 25 **Time Frame:** Baseline up to Week 56 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 27 **Group ID:** BG001 **Value:** 25 **Group ID:** BG002 **Value:** 52 **Units:** Participants ### Group **ID:** BG000 **Title:** TCZ SC 162 mg Q3W **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. ### Group **ID:** BG001 **Title:** TCZ SC 162 mg Q2W **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 2.1 **Value:** 5.5 #### Measurement **Group ID:** BG001 **Spread:** 2.7 **Value:** 13.9 #### Measurement **Group ID:** BG002 **Spread:** 4.9 **Value:** 9.6 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 18 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 36 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 16 **Category Title:** Male **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants **Population Description:** Safety population included all participants who received at least one dose of treatment and who had at least one post-dose safety assessment. ## Results Section - More Information Module ### Certain Agreement **Other Details:** The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Hoffmann-La Roche **Phone:** 800-821-8590 **Title:** Medical Communications ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.21 - **Spread:** - **Upper Limit:** 52.25 - **Value:** 13.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.19 - **Spread:** - **Upper Limit:** 23.75 - **Value:** 12.71 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1465 - **Spread:** - **Upper Limit:** 7708 - **Value:** 2998 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 324 - **Spread:** - **Upper Limit:** 3098 - **Value:** 1933 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 39.37 - **Spread:** - **Upper Limit:** 121.13 - **Value:** 62.44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.56 - **Spread:** - **Upper Limit:** 50.3 - **Value:** 29.74 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 278.376 - **Upper Limit:** - **Value:** 77.569 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 11.24 - **Upper Limit:** - **Value:** 10.567 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 108.157 - **Upper Limit:** - **Value:** -15.309 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.555 - **Upper Limit:** - **Value:** 4.575 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 116.587 - **Upper Limit:** - **Value:** -16.181 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.33 - **Upper Limit:** - **Value:** 11.932 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 15 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 157.295 - **Upper Limit:** - **Value:** 17.998 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 23.935 - **Upper Limit:** - **Value:** 23.223 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 186.212 - **Upper Limit:** - **Value:** 17.265 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 64.907 - **Upper Limit:** - **Value:** 35.263 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 17 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 49.964 - **Upper Limit:** - **Value:** 21.751 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 198.038 - **Upper Limit:** - **Value:** -12.801 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 26.322 - **Upper Limit:** - **Value:** 15.944 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 271.409 - **Upper Limit:** - **Value:** -0.412 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 34.515 - **Upper Limit:** - **Value:** 17.841 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 294.169 - **Upper Limit:** - **Value:** -45.569 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 28.727 - **Upper Limit:** - **Value:** 17.236 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 16 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 65.094 - **Upper Limit:** - **Value:** 32.644 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 24.026 - **Upper Limit:** - **Value:** 14.66 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 14 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 318.217 - **Upper Limit:** - **Value:** -46.575 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 31.747 - **Upper Limit:** - **Value:** 24.478 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 13 - **Group ID:** OG001 - **Value:** 20 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 53.23 - **Upper Limit:** - **Value:** 27.934 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 285.831 - **Upper Limit:** - **Value:** -53.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 82.547 - **Upper Limit:** - **Value:** 36.06 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 16 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 280.041 - **Upper Limit:** - **Value:** -42.836 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 22.712 - **Upper Limit:** - **Value:** 19.397 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 17 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 299.59 - **Upper Limit:** - **Value:** -51.899 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.247 - **Upper Limit:** - **Value:** 20.642 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 15 - **Group ID:** OG001 - **Value:** 19 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 16.665 - **Upper Limit:** - **Value:** 11.958 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 312.758 - **Upper Limit:** - **Value:** -21.565 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 122.88 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 17 - **Group ID:** OG001 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 293.156 - **Upper Limit:** - **Value:** -16.408 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.762 - **Upper Limit:** - **Value:** 14.206 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 20 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 303.851 - **Upper Limit:** - **Value:** -38.921 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 24.814 - **Upper Limit:** - **Value:** 13.273 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 16 - **Group ID:** OG001 - **Value:** 16 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18.458 - **Upper Limit:** - **Value:** 14.765 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 20 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 289.698 - **Upper Limit:** - **Value:** -44.611 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18.455 - **Upper Limit:** - **Value:** 10.401 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 17 - **Group ID:** OG001 - **Value:** 20 **Units:** Participants #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 225.72 - **Upper Limit:** - **Value:** 140.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 241.69 - **Upper Limit:** - **Value:** 206.7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 20 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 41.14 - **Upper Limit:** - **Value:** -4.04 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 29.68 - **Upper Limit:** - **Value:** 1.78 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 53.39 - **Upper Limit:** - **Value:** -1.45 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 51.71 - **Upper Limit:** - **Value:** 4.58 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 16 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 75.29 - **Upper Limit:** - **Value:** 89.72 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 66.75 - **Upper Limit:** - **Value:** 68.90 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** The data was not available as single participant was evaluated. - **Group ID:** OG000 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** 323.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 143.28 - **Upper Limit:** - **Value:** 194.46 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 100.58 - **Upper Limit:** - **Value:** 124.65 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 158.69 - **Upper Limit:** - **Value:** 193.25 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 237.02 - **Upper Limit:** - **Value:** 418.54 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 20 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 194.47 - **Upper Limit:** - **Value:** 239.86 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 344.44 - **Upper Limit:** - **Value:** 407.36 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 234.92 - **Upper Limit:** - **Value:** 233.82 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 20 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 317.77 - **Upper Limit:** - **Value:** 464.77 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 260.33 - **Upper Limit:** - **Value:** 286.06 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 17 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 280.99 - **Upper Limit:** - **Value:** 461.85 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 253.45 - **Upper Limit:** - **Value:** 245.05 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 17 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 299.43 - **Upper Limit:** - **Value:** 482.55 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 230.86 - **Upper Limit:** - **Value:** 274.85 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 17 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 254.46 - **Upper Limit:** - **Value:** 268.72 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 345.97 - **Upper Limit:** - **Value:** 461.19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 257.08 - **Upper Limit:** - **Value:** 244.53 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 303.29 - **Upper Limit:** - **Value:** 514.89 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 234.7 - **Upper Limit:** - **Value:** 256.47 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 276.35 - **Upper Limit:** - **Value:** 494.05 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 229.2 - **Upper Limit:** - **Value:** 292.29 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 - **Group ID:** OG001 - **Value:** 20 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 241.9 - **Upper Limit:** - **Value:** 272.93 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 295.29 - **Upper Limit:** - **Value:** 497.21 - **Comment:** The data was not available as single participant was evaluated. - **Group ID:** OG001 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** 200 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 20 - **Group ID:** OG001 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 270.07 - **Upper Limit:** - **Value:** 532.81 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 20 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 286.78 - **Upper Limit:** - **Value:** 295.28 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 305.07 - **Upper Limit:** - **Value:** 416.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 276.03 - **Upper Limit:** - **Value:** 269.32 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 18 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 299.72 - **Upper Limit:** - **Value:** 243.93 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 263.38 - **Upper Limit:** - **Value:** 470.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 318.38 - **Upper Limit:** - **Value:** 209.51 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 20 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.27 - **Upper Limit:** - **Value:** 3.391 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.908 - **Upper Limit:** - **Value:** 3.356 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 27 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.270 - **Upper Limit:** - **Value:** -2.187 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.21 - **Upper Limit:** - **Value:** -3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.735 - **Upper Limit:** - **Value:** -2.368 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 27 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.346 - **Upper Limit:** - **Value:** -3.069 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 27 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.285 - **Upper Limit:** - **Value:** -3.16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.559 - **Upper Limit:** - **Value:** -1.783 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 27 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.377 - **Upper Limit:** - **Value:** -3.213 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 26 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.158 - **Upper Limit:** - **Value:** -1.336 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.279 - **Upper Limit:** - **Value:** -3.122 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 27 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.455 - **Upper Limit:** - **Value:** -2.467 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.492 - **Upper Limit:** - **Value:** -3.254 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.316 - **Upper Limit:** - **Value:** -2.209 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 25 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.47 - **Upper Limit:** - **Value:** -2.039 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.385 - **Upper Limit:** - **Value:** -3.153 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 26 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.453 - **Upper Limit:** - **Value:** -3.344 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 25 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.285 - **Upper Limit:** - **Value:** -2.225 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 14.2 - **Upper Limit:** - **Value:** 15.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.1 - **Upper Limit:** - **Value:** 13 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 27 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** -7.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.8 - **Upper Limit:** - **Value:** -10.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.5 - **Upper Limit:** - **Value:** -7.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 26 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.9 - **Upper Limit:** - **Value:** -9.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 25 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.4 - **Upper Limit:** - **Value:** -9.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13 - **Upper Limit:** - **Value:** -6.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 26 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.3 - **Upper Limit:** - **Value:** -11.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 26 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 11.2 - **Upper Limit:** - **Value:** -7.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 25 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.2 - **Upper Limit:** - **Value:** -11.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 27 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 14.2 - **Upper Limit:** - **Value:** -8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.8 - **Upper Limit:** - **Value:** -11.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.1 - **Upper Limit:** - **Value:** -8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 26 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13 - **Upper Limit:** - **Value:** -10.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.2 - **Upper Limit:** - **Value:** -12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 26 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 13 - **Upper Limit:** - **Value:** -12.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 25 - **Group ID:** OG001 - **Value:** 0 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.2 - **Upper Limit:** - **Value:** -8.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 0 - **Group ID:** OG001 - **Value:** 22 **Units:** Participants #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016, 2022, 2064, 2112, 2160, 2520 hours post Day 1 dose (additionally at 6, 12, 48, 120, 2028 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016, 2022, 2028, 2040, 2064, 2112, 2160, 2520 hours post Day 1 dose. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic population included all enrolled participants who were adherent to the protocol. **Reporting Status:** POSTED **Time Frame:** Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section) **Title:** Minimum Serum Concentration (Cmin) of TCZ at Steady State **Type:** PRIMARY **Unit of Measure:** Micrograms/milliliter (mcg/mL) ##### Group **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** OG000 **Title:** TCZ SC 162 mg Q3W ##### Group **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. **ID:** OG001 **Title:** TCZ SC 162 mg Q2W #### Outcome Measure 2 **Description:** Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016 hours post Day 1 dose (additionally at 6, 12, 48, 120 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016 post Day 1 dose. **Dispersion Type:** Full Range **Parameter Type:** MEAN **Population Description:** Pharmacokinetic population. **Reporting Status:** POSTED **Time Frame:** Pre-dose (Hour 0) up to 2016 hours post Day 1 dose (detailed timeframe is provided in outcome description section) **Title:** Area Under the Curve at Steady-state Over a 12-week Interval (AUC12weeks) of TCZ Treatment **Type:** PRIMARY **Unit of Measure:** mcg*day/mL ##### Group **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** OG000 **Title:** TCZ SC 162 mg Q3W ##### Group **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. **ID:** OG001 **Title:** TCZ SC 162 mg Q2W #### Outcome Measure 3 **Description:** Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016, 2022, 2064, 2112, ,2160, 2520 hours post Day 1 dose (additionally at 6, 12, 48, 120, 2028 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016, 2022, 2028, 2040, 2064, 2112, 2160, 2520 hours post Day 1 dose. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** Pharmacokinetic population **Reporting Status:** POSTED **Time Frame:** Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section) **Title:** Maximum Serum Concentration (Cmax) of TCZ at Steady State **Type:** PRIMARY **Unit of Measure:** mcg/mL ##### Group **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** OG000 **Title:** TCZ SC 162 mg Q3W ##### Group **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. **ID:** OG001 **Title:** TCZ SC 162 mg Q2W #### Outcome Measure 4 **Description:** IL-6 is a cytokine associated with disease activity in juvenile idiopathic arthritis (JIA) including the polyarticular juvenile idiopathic arthritis (pJIA) subset. It is found in high levels in the synovial fluid and is associated with indicators of inflammatory activity. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety population. Here Number of participants analyzed represents participants evaluable for this outcome measure. Number Analyzed represents participants evaluable for the specified category. **Reporting Status:** POSTED **Time Frame:** Baseline, Days 0.25, 0.5, 2, 4, 5, 84.25, 84.5, 85, 86, 88, 90; Weeks 2, 3, 4, 6, 12, 14, 15, 27, 28, 36, 44, 52 **Title:** Change From Baseline in Serum Interleukin-6 (IL-6) Levels **Type:** SECONDARY **Unit of Measure:** picograms/milliliter (pg/mL) ##### Group **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** OG000 **Title:** TCZ SC 162 mg Q3W ##### Group **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. **ID:** OG001 **Title:** TCZ SC 162 mg Q2W #### Outcome Measure 5 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety population. Here Number of participants analyzed represents participants evaluable for this outcome measure. Number Analyzed represents participants evaluable for the specified category. **Reporting Status:** POSTED **Time Frame:** Baseline, Days 0.25, 0.5, 2, 4, 5, 84.25, 84.5, 85, 86, 88, 90; Weeks 2, 3, 4, 6, 12, 14, 15, 27, 28, 36, 44, 52 **Title:** Change From Baseline in Soluble IL-6 Receptor Levels **Type:** SECONDARY **Unit of Measure:** nanograms per milliliter (ng/mL) ##### Group **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** OG000 **Title:** TCZ SC 162 mg Q3W ##### Group **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. **ID:** OG001 **Title:** TCZ SC 162 mg Q2W #### Outcome Measure 6 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety population. Number Analyzed represents participants evaluable for the specified category. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 4, 6, 9, 12,18, 20, 27, 28, 36, 44, 45, 51, 52 **Title:** Change From Baseline in C-Reactive Protein (CRP) Levels **Type:** SECONDARY **Unit of Measure:** mg/L ##### Group **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** OG000 **Title:** TCZ SC 162 mg Q3W ##### Group **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. **ID:** OG001 **Title:** TCZ SC 162 mg Q2W #### Outcome Measure 7 **Description:** The ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline indicates improvement. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety population. Number Analyzed represents participants evaluable for the specified category. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 4, 6, 9, 12, 18, 20, 27, 28, 36, 44, 45, 51, 52 **Title:** Change From Baseline in Erythrocyte Sedimentation Rate (ESR) **Type:** SECONDARY **Unit of Measure:** millimeters per hour (mm/h) ##### Group **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** OG000 **Title:** TCZ SC 162 mg Q3W ##### Group **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 Weeks. **ID:** OG001 **Title:** TCZ SC 162 mg Q2W #### Outcome Measure 8 **Parameter Type:** NUMBER **Population Description:** Safety population. **Reporting Status:** POSTED **Time Frame:** Baseline up to Week 52 **Title:** Percentage of Participants With Anti-TCZ Antibodies of Neutralizing Potential **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants with body weight \< 30 kg were administered 162 mg of TCZ as an SC injection Q3W for 52 weeks. **ID:** OG000 **Title:** TCZ SC 162 mg Q3W ##### Group **Description:** Participants with body weight \>/= 30 kg were administered 162 mg of TCZ as an SC injection Q2W for 52 weeks. **ID:** OG001 **Title:** TCZ SC 162 mg Q2W ### Participant Flow Module #### Group **Description:** Participants with body weight less than (\<) 30 kilograms (kg) were administered 162 milligrams (mg) of TCZ as an subcutaneous (SC) injection every 3 weeks (Q3W) for 52 weeks. **ID:** FG000 **Title:** TCZ SC 162 mg Q3W #### Group **Description:** Participants with body weight greater than or equal to (\>/=) 30 kg were administered 162 mg of TCZ as an SC injection every 2 weeks (Q2W) for 52 weeks. **ID:** FG001 **Title:** TCZ SC 162 mg Q2W #### Period **Title:** Overall Study ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 27 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 25 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 24 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 22 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 3 **Recruitment Details:** A total of 52 participants were enrolled in the study. Study included a 21-day screening period. **Has Results:** True
## Protocol Section ### Identification Module **NCT ID:** NCT02407379 **Acronym:** PAPD **Brief Title:** Diode Laser and SRP in Chronic Periodontitis **Official Title:** Photoablative-photodynamic (PAPD) Diode Laser Therapy Adjunctive to Scaling and Root Planing in Periodontitis #### Organization Study ID Info **ID:** OLTC014 #### Organization **Class:** OTHER **Full Name:** Odontostomatologic Laser Therapy Center, Florence, Italy ### Status Module #### Completion Date **Date:** 2018-08-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-08-31 **Type:** ACTUAL **Last Update Submit Date:** 2018-08-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-10 **Type:** ACTUAL #### Start Date **Date:** 2015-10 **Status Verified Date:** 2018-08 #### Study First Post Date **Date:** 2015-04-03 **Type:** ESTIMATED **Study First Submit Date:** 2014-07-09 **Study First Submit QC Date:** 2015-04-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Odontostomatologic Laser Therapy Center, Florence, Italy #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to compare the efficacy of photoablative and photodynamic diode laser in adjunct to scaling-root planing (PAPD+SRP) and SRP alone for the treatment of periodontitis. **Detailed Description:** The present study is a randomized, blinded, controlled clinical trial, which used a split-mouth design. All patients were informed individually about the nature of the proposed treatment, and informed consent forms were signed. Twenty-four patients were studied. Maxillary left or right quadrants were randomly assigned to PAPD laser treatment or sham-treatment and SRP. PAPD consisted of: i) photoablative gingival epithelium with diode laser (λ 810 nm, 1 W); ii) photodynamic treatments (4-10 weekly) with diode laser (λ 635 nm, 100 mW) and 0.3% methylene blue as photoactive antiseptic, performed after SRP. Sham-treatment was similar but with switched off laser. Efficacy evaluations, including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) was performed at baseline ,1year, and year 3 using a conventional manual periodontal probe. Polymorphonuclear leukocytes (PMN), erythrocytes (RBC), damaged epithelial cells (DEC) and bacteria were assayed by cytofluorescence on gingival exfoliative samples at baseline, 6 month and 1, 3, 5 years. ### Conditions Module **Conditions:** - Periodontitis **Keywords:** - Laser - periodontitis - scaling root planing - bacteria - PMN ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 24 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This quadrant, randomly selected in each patients, undergoes treatment with PAPD+ SRP **Intervention Names:** - Procedure: PAPD+SRP **Label:** PAPD+SRP Quadrant **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** This quadrant, randomly selected in each patients, undergoes treatment with sham-laser + SRP **Intervention Names:** - Procedure: Sham-laser +SRP **Label:** Sham-laser + SRP **Type:** SHAM_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - PAPD+SRP Quadrant **Description:** Photoablation of the gingival epithelium was performed with at 810 nm diode laser (1 W output power, continuous wave mode, 66.7 J/cm2, a 0.6 mm optical fiber). SRP was performed using curettes. The periodontal tissues and the dental root were rinsed with the photosensitizer agent methylene blue (0.3% w/v in water). After 5 min., the treated areas were irradiated with at 635 nm diode laser (100 mW output power, continuous wave mode, 0.6 mm optic fiber). The photodynamic treatment was repeated once weekly until normalization of the cytodiagnostic parameters (range: 4-10 applications). **Name:** PAPD+SRP **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Sham-laser + SRP **Description:** Sham-treatment was similar to the previously described treatment but with switched off laser, followed by scaling and root planing **Name:** Sham-laser +SRP **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Change in probing pocket depth **Measure:** PD **Time Frame:** baseline, 1 year #### Secondary Outcomes **Description:** Change in mean attachment level **Measure:** CAL **Time Frame:** baseline, 1 year **Description:** Change in mean bleeding on probing **Measure:** BoP **Time Frame:** baseline, 1 year **Description:** Change in mean additional disease markers, namely polymorphonuclear leukocytes (PMN), erythrocytes (RBC), damaged epithelial cells (DEC) and bacteria were assayed by cytofluorescence on gingival exfoliative samples. **Measure:** PMN, DEC, bacteria **Time Frame:** baseline, 1 year **Description:** Individual evaluation of pain/discomfort assessed by a visual analogue score interview **Measure:** Patient-reported outcomes **Time Frame:** baseline, 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Periodontitis:Presence of at least two teeth with at least one site with pocket probing depth (PD) ranging from 4 to 10 mm in each upper maxillary quadrant and with bleeding on probing (BOP) 2. A minimum of five natural teeth in each studied quadrant. Exclusion Criteria: 1. History of systemic diseases (diabetes mellitus, cancer, HIV, metabolic and endocrine diseases) 2. Pregnancy or lactation 3. Chronic high-dose steroid use 4. Previous or current radiation or immunosuppressive therapies 5. Ongoing orthodontic treatments 6. Extensive carious lesions 7. Recurrent antibiotic medications during the 6 months preceding the study 8. Class III tooth mobility 9. Heavy contamination by spirochetes and fungal pathogens on tongue and oral mucosa **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Florence **Country:** Italy **Facility:** Odontostomatologic laser therapy center **Zip:** 50143 #### Overall Officials **Official 1:** **Affiliation:** Odontostomatologic laser therapy center **Name:** Marco Giannelli **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Giannelli M, Materassi F, Fossi T, Lorenzini L, Bani D. Treatment of severe periodontitis with a laser and light-emitting diode (LED) procedure adjunctive to scaling and root planing: a double-blind, randomized, single-center, split-mouth clinical trial investigating its efficacy and patient-reported outcomes at 1 year. Lasers Med Sci. 2018 Jul;33(5):991-1002. doi: 10.1007/s10103-018-2441-9. Epub 2018 Jan 18. **PMID:** 29349511 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010510 - Term: Periodontal Diseases - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13427 - Name: Periodontitis - Relevance: HIGH - As Found: Periodontitis - ID: M28044 - Name: Chronic Periodontitis - Relevance: LOW - As Found: Unknown - ID: M13419 - Name: Periodontal Diseases - Relevance: LOW - As Found: Unknown - ID: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010518 - Term: Periodontitis ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Derm - Name: Dermatologic Agents ### Intervention Browse Module - Browse Leaves - ID: M11726 - Name: Methylene Blue - Relevance: LOW - As Found: Unknown - ID: M19608 - Name: Photosensitizing Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT01100879 **Acronym:** AOC-MM **Brief Title:** Ferric Carboxymaltose for Treatment of Anaemia of Cancer in Subjects With Multiple Myeloma Receiving Chemotherapy **Official Title:** Randomised Controlled Open-label Study to Evaluate Efficacy & Safety of Intravenous Ferric Carboxymaltose Versus no Treatment in Anaemic Subjects With Multiple Myeloma & Iron Restricted Erythropoiesis Receiving Chemotherapy #### Organization Study ID Info **ID:** FER-AOC-MM #### Organization **Class:** INDUSTRY **Full Name:** Vifor Pharma ### Status Module #### Completion Date **Date:** 2011-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-05-09 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-03 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2011-07 **Type:** ACTUAL #### Start Date **Date:** 2010-03 **Status Verified Date:** 2011-06 #### Study First Post Date **Date:** 2010-04-09 **Type:** ESTIMATED **Study First Submit Date:** 2010-03-29 **Study First Submit QC Date:** 2010-04-08 **Why Stopped:** Lack of Recruitment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Vifor Pharma #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Multicentre, randomised, controlled, 2-arm open-label prospective pilot study to evaluate efficacy and safety of ferric carboxymaltose (FCM) in treatment of anaemia in subjects with multiple myeloma (MM) initiating chemotherapy. The subjects will be screened for eligibility within 4 weeks prior to inclusion and randomised to receive intravenous infusions of FCM or standard care (the subjects may be treated according to the local institutional practice if requiring symptomatic management of anaemia). Thereafter the visits are scheduled at Weeks 0, 2, 4, 6 and 8. **Detailed Description:** Patients will be randomised into two groups. One will receive active FCM treatment and the other group will receive local standard of care. Active treatment group: Subjects will receive a total dose of 1,000 mg iron as FCM on the day of the first scheduled chemotherapy cycle or within 24 hours before or after receiving chemotherapy. In subjects of weight ≤66 kg, the first dose (500 mg) will be administered on the day of the first scheduled chemotherapy cycle and the second dose (500 mg) on the next study visit. Standard of care group: Subjects will be treated according to the local institutional practice if requiring management of symptomatic anaemia. Intravenous iron should only be used to treat absolute iron deficiency (as defined as ferritin less than the lower limit of normal based on the test reference ranges). Patients with absolute iron deficiency are not eligible for inclusion to the study. Rescue medication to manage anaemia is permitted in both arms at the discretion of the treating physician and/or per institutional practice. ### Conditions Module **Conditions:** - Iron-Deficiency Anemia **Keywords:** - Anemia - Lymphoproliferative Disorders - Chemotherapy - ferric carboxymaltose - iron ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 3 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will receive a total dose of 1,000 mg iron as FCM on the day of the next scheduled chemotherapy cycle after randomisation or continuous chemotherapy. In subjects with weight ≤66 kg, the first dose iron will be 500 mg; the second dose (500 mg) will be administered on the visit 3 (week 2). **Intervention Names:** - Drug: Ferric carboxymaltose **Label:** Ferric carboxymaltose **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Subjects will be treated according to the local institutional practice. **Label:** Local standard of care. **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Ferric carboxymaltose **Description:** Subjects will receive a single dose of 1,000 mg iron as FCM infusion at baseline. Subjects of bw ≤66 kg will receive a single dose of 500 mg iron as FCM infusion at baseline (Week 0) and at Visit 3 (Week 2). Ferric carboxymaltose will be administered on the same day with chemotherapy treatment or within 24 hours before or after the chemotherapy. For subjects with bw ≤66 kg, if no chemotherapy planned for the visit 4 (Week 2), the second FCM dose should be infused independent of chemotherapy. **Name:** Ferric carboxymaltose **Other Names:** - Ferinject **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Mean change in Hb from baseline to Weeks 4, 6 and 8 (end of treatment) in the absence of any red cell transfusion or erythropoiesis stimulating agents (ESA) treatment. **Measure:** Change in haemoglobin (Hb) from baseline to Weeks 4, 6 and 8 **Time Frame:** week 4, 6 and 8 post baseline #### Secondary Outcomes **Description:** Percentage of subjects with blood Hb response of at least 1 g/dL in the absence of any red cell transfusion or ESA treatment. **Measure:** Percentage of subjects with blood Hb response of at least 1 g/dL **Time Frame:** 12 weeks post baseline **Description:** Percentage of subjects with a blood Hb correction to at least 12 g/dL in the absence of any red cell transfusion or ESA treatment **Measure:** Percentage of subjects with a blood Hb correction to at least 12 g/dL **Time Frame:** 12 weeks post baseline **Description:** Median time to Hb response defined as increase in Hb equal to or more than 1 g/dL in the absence of any red cell transfusion or ESA treatment **Measure:** Time to Hb response defined as increase in Hb equal to or more than 1 g/dL **Time Frame:** Baseline until end of study (week 8) **Description:** Proportion of subjects receiving red blood cell transfusions or subjects treated with ESA during the study period **Measure:** Subjects receiving red blood cell transfusions or subjects treated with ESA **Time Frame:** Baseline until end of study (week 8) **Description:** Adverse events: type, nature, incidence and outcome **Measure:** Adverse events **Time Frame:** Baseline until end of study (week 8) **Description:** Time to transfusion/treatment with ESA **Measure:** Transfusion/treatment with ESA **Time Frame:** Baseline until end of study (week 8) **Description:** Mean change in serum ferritin from baseline to Weeks 2, 4, 6 and 8 **Measure:** Change in serum ferritin from baseline to Weeks 2, 4, 6 and 8 **Time Frame:** week 2, 4, 6, and 8 post baseline **Description:** Mean change in TSAT from baseline to Weeks 2, 4, 6 and 8 **Measure:** Change in transferrin saturation (TSAT) from baseline to Weeks 2, 4, 6 and 8 **Time Frame:** week 2, 4, 6, and 8 post baseline **Description:** Mean change in serum iron from baseline to Weeks 2, 4, 6 and 8 **Measure:** Change in serum iron from baseline to Weeks 2, 4, 6 and 8 **Time Frame:** week 2, 4, 6, and 8 post baseline **Description:** Mean change in endogenous erythropoietin from baseline to Weeks 2, 4, 6 and 8 **Measure:** Change in endogenous erythropoietin from baseline to Weeks 2, 4, 6 and 8 **Time Frame:** week 2, 4, 6, and 8 post baseline **Description:** Mean change in blood reticulocyte haemoglobin content/red blood cell size factor from baseline to Weeks 2, 4, 6 and 8 **Measure:** Change in blood reticulocyte haemoglobin content/red blood cell size factor from baseline to Weeks 2, 4, 6 and 8 **Time Frame:** week 2, 4, 6, and 8 post baseline **Description:** Mean change in percentage of hypochromic red cells/percentage of low Hb density from baseline to Weeks 2, 4, 6 and 8 **Measure:** Change in percentage of hypochromic red cells/percentage of low Hb density from baseline to Weeks 2, 4, 6 and 8 **Time Frame:** week 2, 4, 6, and 8 post baseline **Description:** Mean change in hepcidin from baseline to Weeks 2, 4, 6 and 8 **Measure:** Change in hepcidin from baseline to Weeks 2, 4, 6 and 8 **Time Frame:** week 2, 4, 6, and 8 post baseline **Description:** Mean change in interleukin-6 from baseline to Weeks 2, 4, 6 and 8 **Measure:** Change in interleukin-6 from baseline to Weeks 2, 4, 6 and 8 **Time Frame:** week 2, 4, 6, and 8 post baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects (male or female) aged ≥18, suffering from a newly diagnosed or progressed/relapsed MM and scheduled to receive anti-myeloma treatment. Progression is defined according to "Uniform Response Criteria for Multiple Myeloma" * Subjects with progressed/relapsed MM should have had stable disease (during the last 6 months since prior treatment). * Life expectancy at least 6 months. * 8.5 g/dL ≤Hb ≤11 g/dL at time of randomisation. * Iron-restricted erythropoiesis as defined: * Stainable iron in bone marrow (BM) combined with transferrin saturation (TSAT) ≤20%, or * where the evaluation of stainable iron in BM is not possible or available: * ferritin \>30 ng/mL (women) or \>40 ng/mL (men), and * TSAT ≤20% * Females of child-bearing potential must have a negative urine pregnancy test at screening. * Before any study-specific procedure, the appropriate written informed consent must be obtained. Exclusion Criteria: * Any anaemia treatment within 4 weeks prior to randomisation (including red blood cell transfusions, treatment with ESA or any oral/parenteral iron preparations). * Anthracycline containing chemotherapy regimens. * Subjects weighing \<35 kg. * Folate deficiency (serum-folate \<4.5 nmol/L) and/or Vitamin B12 deficiency (serum-cobalamin \<145 pmol/L). * Ongoing haemolysis defined as serum-haptoglobin \<0.2 g/L. * Known chronic renal failure, glomerular filtration rate \<30 mL/min/m2. * Recent (within last 4 weeks) significant bleeding/surgery, defined as drop in Hb of ≥2 g/dL. * Clinically relevant active inflammatory disease other than MM (according to the judgement of the Investigator). * Clinically relevant ongoing infectious disease including known human immunodeficiency virus. * Serum ferritin \>600 ng/mL. * Ongoing significant neurological or psychiatric disorders including psychotic disorders or dementia. * Significant cardiovascular disease prior to study inclusion including myocardial infarction within 12 months prior to study inclusion, congestive heart failure New York Heart Association Grade III or IV, or poorly controlled hypertension according to the judgment of the Investigator. * Elevation of liver enzymes (aspartate aminotransferase, alanine aminotransferase) over 3 times above the normal range or known acute hepatic disorder. * Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s). * Subject of child-bearing potential is evidently pregnant (e.g., positive human chorionic gonadotropin test) or is breast feeding. * Subject is not using adequate contraceptive precautions. Adequate contraceptive precautions are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomised partner. Non-childbearing potential includes being surgically sterilised at least 6 months prior to the study or post-menopausal, defined as amenorrhea for at least 12 months. * Subject has known sensitivity to any of the products to be administered during dosing. * Subject will not be available for follow-up assessment. * Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Rennes **Country:** France **Facility:** Hopital Sud **Zip:** 35203 **Location 2:** **City:** Thessaloniki **Country:** Greece **Facility:** Theagenion Cancer Center **Zip:** 54007 #### Overall Officials **Official 1:** **Affiliation:** Theagenion Hospital, Thessaloniki, Greece **Name:** Katodritou Eirini, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Vifor Pharma, CH-8152 Glattbrugg, Switzerland **Name:** Timothy R Cushway **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000054219 - Term: Neoplasms, Plasma Cell - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000020141 - Term: Hemostatic Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010265 - Term: Paraproteinemias - ID: D000001796 - Term: Blood Protein Disorders - ID: D000006402 - Term: Hematologic Diseases - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000019189 - Term: Iron Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000000747 - Term: Anemia, Hypochromic ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12058 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: M27588 - Name: Neoplasms, Plasma Cell - Relevance: LOW - As Found: Unknown - ID: M20857 - Name: Anemia, Iron-Deficiency - Relevance: HIGH - As Found: Iron Deficiency Anemia - ID: M2781 - Name: Iron Deficiencies - Relevance: HIGH - As Found: Iron Deficiency - ID: M4070 - Name: Anemia - Relevance: HIGH - As Found: Anemia - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M13178 - Name: Paraproteinemias - Relevance: LOW - As Found: Unknown - ID: M5077 - Name: Blood Protein Disorders - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M21177 - Name: Iron Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M4077 - Name: Anemia, Hypochromic - Relevance: LOW - As Found: Unknown - ID: T3947 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma ### Condition Browse Module - Meshes - ID: D000009101 - Term: Multiple Myeloma - ID: D000000740 - Term: Anemia - ID: D000018798 - Term: Anemia, Iron-Deficiency - ID: D000090463 - Term: Iron Deficiencies ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10533 - Name: Iron - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT00292279 **Brief Title:** The Impact of Omega-3 Fat Emulsion on Clinical Outcome of Post-Operative Cancer Patients **Official Title:** The Impact of Omega-3 Fat Emulsion on Clinical Outcome of Post-Operative Cancer Patients: A Randomized, Double Blind, Controlled, Multi-Center Clinical Trial. #### Organization Study ID Info **ID:** HL20020004 #### Organization **Class:** INDUSTRY **Full Name:** Fresenius Kabi Sino-Swed Pharmaceutical Corp. Ltd ### Status Module #### Completion Date **Date:** 2004-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2008-05-14 **Type:** ESTIMATED **Last Update Submit Date:** 2008-05-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2003-11 **Type:** ACTUAL #### Start Date **Date:** 2002-06 **Status Verified Date:** 2008-05 #### Study First Post Date **Date:** 2006-02-15 **Type:** ESTIMATED **Study First Submit Date:** 2006-02-13 **Study First Submit QC Date:** 2006-02-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Sino-Swed Pharmaceutical Corporation #### Responsible Party **Old Name Title:** TF Ye **Old Organization:** Ethic Committee of Peking Union Medical College Hospital ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to evaluate clinical safety and effect of Omega-3 fat oil emulsion on outcome in post-operative cancer patients. **Detailed Description:** As an essential component of parenteral nutrition, fat emulsion has been used more than 30 years. It provides energy and essential fatty acids. Commercial fatty emulsion products mostly come from soy bean. The omega 6 fatty acids make up with the major fatty acids of this fat emulsion, and lack of omega 3 fatty acids generally. The imbalance of these two types of fatty acids may impact with negative clinical outcomes. There are lots of omega 3 fatty acids makes up with fish oil emulsion, especially with eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA).Few clinical studies found its clinical efficacy in recently years. A commercial product of omega 3 fat emulsion by Fresenius-Kabi was registered in Europe at 1998. There is no any clinical trial in Asia to elaborate the efficacy of omega 3 fat emulsion, as well the lack of large scale clinical trial in the world. Currently study is the first large scale, randomized, double blind and multi-center clinical trial to elaborate the impact of fish oil fat emulsion in Asia and Europe. ### Conditions Module **Conditions:** - Carcinoma Surgery - Parenteral Nutrition - Post-Operative Hospital Stay **Keywords:** - Impact of Omega 3 fatty acid on outcome - Omega-3 fatty acid - Carcinoma surgery - Digestive System - Parenteral Nutrition - Fat Emulsions, Intravenous - Clinical outcome - SIRS - Infectious complication - Postoperative hospital stay - Cost of postoperative period - Post-operative nutritional cost & total treatment cost ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 206 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Omega-3 fish oil emulsion (Omegaven ) **Label:** A **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: long-chain triglyceride **Label:** B **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - A **Description:** Patients of the treatment group received 0.2 g fish oil (10% Omegaven, Fresenius Kabi, Bad Homburg, Germany) and 1.0 g soy bean oil per kg BW per day **Name:** Omega-3 fish oil emulsion (Omegaven ) **Other Names:** - Omegaven **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - B **Description:** the control group received 1.2 g soy bean oil (Intralipid, Sino-Swed,Wuxi,China) **Name:** long-chain triglyceride **Other Names:** - Intralipid **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Infectious complication **Time Frame:** POD+1 to POD+14 **Measure:** Systemic inflammatory response syndrome (SIRS) **Time Frame:** POD+1 to POD +8 #### Secondary Outcomes **Measure:** Post-operative hospitalization days **Time Frame:** POD+1 to discharge **Measure:** Post operative nutritional cost & total treatment cost **Time Frame:** POD+1 to discharge ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Post-operative male and female cancer patients * Require post operative parenteral nutrition support at least 7 days based on nutritional risk screening(BMI 20-25) * Sign an informed consent Exclusion Criteria: * Diabetes Mellitus * Abnormal fatty metabolism (TG\>200mg/dl or cholesterol\>240mg/dl ) * Renal dysfunction (Cr\>1.6mg/dl or BUN\>30mg/dl) * Liver dysfunction (ALT\>60U/L or TBIL\>1.2mg/dl) * Lienectomy * Temperature\>37.5°C * Undergoing hormone therapy * Pregnancy **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Beijing **Country:** China **Facility:** People's Hospital, Beijing University **Zip:** 100044 **Location 2:** **City:** Beijing **Country:** China **Facility:** Beijing Friendship Hospital **Zip:** 100050 **Location 3:** **City:** Beijing **Country:** China **Facility:** Beijing Hospital **Zip:** 100730 **Location 4:** **City:** Beijing **Country:** China **Facility:** Peking Union Medical College Hospital **Zip:** 100730 **Location 5:** **City:** Beijing **Country:** China **Facility:** General Hospital Of PLA **Zip:** 100853 #### Overall Officials **Official 1:** **Affiliation:** Peking Union Medical College Hospital **Name:** Zhu-ming Jiang, FACS **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** (Abstract) ZM Jiang, XR Wang, JM Wei, Y. Wang, Y. Li, S Wang, DW Wilmore. The impact of i.v. fish oil emulsion on clinical outcome & immune functions of post-operative cancer patients: a randomized, double blind, controlled, multi-center clinical trial for 203 cases Clinical Nutrition(Abstract for ESPEN 2005)(Absract No. 181) **Citation:** Jiang ZM, Wilmore DW, Wang XR, Wei JM, Zhang ZT, Gu ZY, Wang S, Han SM, Jiang H, Yu K. Randomized clinical trial of intravenous soybean oil alone versus soybean oil plus fish oil emulsion after gastrointestinal cancer surgery. Br J Surg. 2010 Jun;97(6):804-9. doi: 10.1002/bjs.6999. **PMID:** 20473991 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC04 - Name: Neoplasms ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma ### Intervention Browse Module - Ancestors - ID: D000005217 - Term: Fat Emulsions, Intravenous - ID: D000057947 - Term: Parenteral Nutrition Solutions - ID: D000019999 - Term: Pharmaceutical Solutions ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Ot - Name: Other Dietary Supplements - Abbrev: HB - Name: Herbal and Botanical ### Intervention Browse Module - Browse Leaves - ID: M8360 - Name: Fat Emulsions, Intravenous - Relevance: LOW - As Found: Unknown - ID: M223889 - Name: Soybean oil, phospholipid emulsion - Relevance: HIGH - As Found: Mimic - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M28934 - Name: Parenteral Nutrition Solutions - Relevance: LOW - As Found: Unknown - ID: T415 - Name: Omega 3 Fatty Acid - Relevance: LOW - As Found: Unknown - ID: T294 - Name: Soy Bean - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000545823 - Term: Soybean oil, phospholipid emulsion ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04460079 **Brief Title:** Safety and Effectiveness Assessment of PeGagen® (Pegfilgrastim) in the Prevention of Chemotherapy-induced FN **Official Title:** Safety and Effectiveness Assessment of PeGagen® (Pegfilgrastim) in the Prevention of Chemotherapy-induced Febrile Neutropenia in Iranian Cancer Patients #### Organization Study ID Info **ID:** PEGAGEN.CIN.AJ.95 (IV) #### Organization **Class:** INDUSTRY **Full Name:** Cinnagen ### Status Module #### Completion Date **Date:** 2019-09-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-07-07 **Type:** ACTUAL **Last Update Submit Date:** 2020-07-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-09-07 **Type:** ACTUAL #### Start Date **Date:** 2016-03-29 **Type:** ACTUAL **Status Verified Date:** 2020-05 #### Study First Post Date **Date:** 2020-07-07 **Type:** ACTUAL **Study First Submit Date:** 2020-06-27 **Study First Submit QC Date:** 2020-07-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Cinnagen #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The present study was an observational, multicenter, non-interventional, single arm, open label, PMS study conducted in Iran. The primary objective of this study was safety assessment, including the rate of AEs. The secondary objective was the effectiveness evaluation in the prevention of chemotherapy-induced FN. **Detailed Description:** The present study was an observational, multicenter, non-interventional, single arm, open label, PMS study conducted in Iran. Data was gathered in two booklets, each containing information on four cycles of chemotherapy, which was filled by the designated physician. The duration of PegaGen® treatment was at the physicians' discretion based on the patient's condition. The primary objective of this study was safety assessment, including the rate of AEs. The secondary objective was the effectiveness evaluation in the prevention of chemotherapy-induced FN. This study was single arm and 654 subjects participated across various tumor types and regimens. ### Conditions Module **Conditions:** - Chemotherapy-induced Neutropenia **Keywords:** - Febrile neutropenia - Pegfilgrastim - Post-marketing surveillance - Chemotherapy-induced neutropenia - myelosuppressive chemotherapy ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 654 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** PegaGen® was injected as a single subcutaneous dose after completion of cytotoxic chemotherapy **Name:** Peg-filgrastim **Other Names:** - PegaGen® **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Safety evaluation was reported using summary statistics. For each AE, data was summarized using incidence according to system organ class and preferred term of AEs and SAEs. Moreover, causality assessment was done and its results was reported by frequency and percentage. **Measure:** Safety assessment, using incidence according to SOC and PT of AEs and SAEs **Time Frame:** This outcome was assessed throughout the study, up to 8 chemotherapy cycles. The duration of treatment was at the physicians' discretion based on the patient's condition. #### Secondary Outcomes **Description:** The frequency of neutropenia and neutropenic fever was reported **Measure:** Effectiveness assessment: The frequency of neutropenia and neutropenic fever **Time Frame:** This outcome was assessed throughout the study, up to 8 chemotherapy cycles. The duration of treatment was at the physicians' discretion based on the patient's condition. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients aged ≥18 years, * with the diagnosis of various types of cancers (such as lymphoma, breast, lung, testicular, prostate, ovary and gastrointestinal cancers), receiving first-line chemotherapy regimens with a high FN risk, which PegaGen® is injected due to physician decision. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients receiving various tumor types and regimens with chemotherapy regimens of high FN risk, will be included. ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Oncology & Hematology Dep., Booali Hosp., Islamic Azad University, Tehran, Iran **Name:** Arash Jenabian, Professor **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Jenabian A, Ehsanpour A, Mortazavizadeh SMR, Raafat J, Razavi M, Khosravi A, Seifi S, Salimi B, Anjidani N, Kafi H. Evaluating the safety and effectiveness of PegaGen(R) (pegfilgrastim) for the prevention of chemotherapy-induced febrile neutropenia: a post-marketing surveillance study. Support Care Cancer. 2022 Oct;30(10):8151-8158. doi: 10.1007/s00520-022-07265-2. Epub 2022 Jul 6. **PMID:** 35792924 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000000380 - Term: Agranulocytosis - ID: D000007970 - Term: Leukopenia - ID: D000095542 - Term: Cytopenia - ID: D000006402 - Term: Hematologic Diseases - ID: D000007960 - Term: Leukocyte Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12443 - Name: Neutropenia - Relevance: HIGH - As Found: Neutropenia - ID: M2454 - Name: Hyperthermia - Relevance: LOW - As Found: Unknown - ID: M8464 - Name: Fever - Relevance: LOW - As Found: Unknown - ID: M30221 - Name: Febrile Neutropenia - Relevance: HIGH - As Found: Febrile Neutropenia - ID: M30220 - Name: Chemotherapy-Induced Febrile Neutropenia - Relevance: LOW - As Found: Unknown - ID: M3730 - Name: Agranulocytosis - Relevance: LOW - As Found: Unknown - ID: M10973 - Name: Leukopenia - Relevance: LOW - As Found: Unknown - ID: M3170 - Name: Cytopenia - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M10963 - Name: Leukocyte Disorders - Relevance: LOW - As Found: Unknown - ID: T2606 - Name: Granulocytopenia - Relevance: HIGH - As Found: Neutropenia ### Condition Browse Module - Meshes - ID: D000009503 - Term: Neutropenia - ID: D000064147 - Term: Febrile Neutropenia ### Intervention Browse Module - Ancestors - ID: D000000276 - Term: Adjuvants, Immunologic - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1945 - Name: Lenograstim - Relevance: HIGH - As Found: 30 minutes - ID: M3628 - Name: Adjuvants, Immunologic - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000078224 - Term: Lenograstim ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT04339179 **Acronym:** INA-ORCHID **Brief Title:** Observational Research on Infectious Disease Outbreaks and Difficult Cases of Unidentified Etiology in Indonesia **Official Title:** INA-RESPOND Observational Research on Infectious Disease Outbreaks and Difficult Cases of Unidentified Etiology in Indonesia #### Organization Study ID Info **ID:** INA107 #### Organization **Class:** OTHER **Full Name:** Ina-Respond #### Secondary ID Infos **Domain:** WHO UTN Number **ID:** U1111-1263-1317 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-08-24 **Type:** ACTUAL **Last Update Submit Date:** 2022-08-23 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2020-11-18 **Type:** ACTUAL **Status Verified Date:** 2022-08 #### Study First Post Date **Date:** 2020-04-09 **Type:** ACTUAL **Study First Submit Date:** 2020-04-06 **Study First Submit QC Date:** 2020-04-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ina-Respond #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This observational study will investigate suspected infectious diseases of unknown etiology prospectively during outbreaks and at healthcare facilities, and retrospectively through historical samples where no etiology was ever determined. The study is designed to rapidly, flexibly, and consistently respond to any potential scenario in Indonesia, and the data collected will provide needed insight into the landscape of infectious diseases in the country. By better understanding the infectious causes of outbreaks and difficult hospitalized cases, the Indonesian Ministry of Health will be able to more accurately and efficiently control infectious diseases and craft healthcare policies. **Detailed Description:** This is a study to identify the causative agents and describe the clinical characteristics of infectious disease outbreaks and difficult cases of unidentified etiology in Indonesia. It is a retrospective and prospective observational study with an exploratory design. There will be no intervention to the participants that is intended to affect their SoC or clinical outcome. Retrospective study activities will be ongoing throughout the duration of the study. The INA-RESPOND Reference Lab will perform research tests on various specimens collected as part of historical outbreaks and previous difficult cases where an etiology was never identified. Prospective study activities will be initiated upon official request from health authorities and health facilities/institutions. Requests are expected to be filtered through and evaluated by the 19 active INA-RESPOND Network sites before inclusion in the study. Samples collected during outbreaks and from difficult cases of unknown etiology will be analyzed at the INA-RESPOND Reference Lab at their own pace. Results from any research tests will be shared with the requesting authorities as research-use-only and are not intended to alter standard of care. ### Conditions Module **Conditions:** - Infectious Disease **Keywords:** - Infectious Disease ### Design Module #### Bio Spec **Description:** whole blood, sputum, urine, stool, nasopharyngeal swab **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 2500 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** The etiologies (bacteria, viruses, parasites, fungi and others) of illness determined by Reference Laboratory tests expressed in percentages of enrolled subjects. **Measure:** To identify the causative agents and describe the clinical characteristics of presumptive infections reported during infectious diseases outbreaks or referred from difficult cases of unidentified etiology in Indonesia. **Time Frame:** [Time Frame: 5 years] [No Safety Issue] #### Secondary Outcomes **Description:** Signs, symptoms, and clinical laboratory data from each confirmed diagnosis calculated in percentages. **Measure:** To describe the disease course and case management of the presumptive infections **Time Frame:** [Time Frame: 5 years] [No Safety Issue] **Description:** The etiologies (bacteria, viruses, parasites, fungi and others) of illness determined by both point-of-care diagnostic tests and Reference Laboratory tests expressed as ratios. **Measure:** To assess the accuracy of diagnostic tests of the presumptive infections **Time Frame:** [Time Frame: 5 years] [No Safety Issue] **Description:** Enrolled subject condition at end of study and duration of illness from enrollment to end of study. **Measure:** To assess treatments and short-term outcomes of the presumptive infections **Time Frame:** [Time Frame: 5 years] [No Safety Issue] **Description:** The etiologies (bacteria, viruses, parasites, fungi and others) of illness determined by Reference Laboratory tests expressed in percentages of enrolled subjects. **Measure:** To generate epidemiologic data to inform ongoing and future disease control and prevention efforts **Time Frame:** [Time Frame: 5 years] [No Safety Issue] ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Adult or child of any age hospitalized with a current episode of illness with a presumed infectious disease of unidentified etiology 2. Negative for Dengue virus infection by an antigen-based and antibody-based diagnostic test (i.e. NS1 antigen test and Dengue-specific IgM test) 3. Negative for Salmonella Typhi infection by Standard of Care testing (i.e. blood culture, Widal test, or Tubex rapid test) 4. Able to provide a documented informed consent 5. Agrees to the collection and storage of specimens for laboratory testing and/or future research (participants may decline storage of specimens for future research) 6. For Ongoing patients in outbreak situations: Referral from the MoH as part of a suspected or identified outbreak of infectious disease Exclusion Criteria: * Investigators' discretion for patient safety and well being **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Adult or child of any age, both men and women hospitalized with a current episode of illness with a presumed infectious disease of unidentified etiology or referral from the MoH as part of a suspected or identified outbreak of infectious disease from 19 active INA-RESPOND Network sites across Indonesia ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Dr. Muhammad Karyana, MPH **Phone:** +62 21 42879189 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** dr. Dona Arlinda, M.Sc. **Phone:** +62 21 42879189 **Role:** CONTACT #### Locations **Location 1:** **City:** Denpasar **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Prof. Dr. Ketut Tuti Merati, SpPD-KPTI - **Phone:** +62361246274 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr. dr. Agus Somya Sp.PD (KPTI) - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 520: University of Udayana/Sanglah Hospital **State:** Bali **Status:** NOT_YET_RECRUITING **Zip:** 80114 **Location 2:** **City:** Semarang **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Prof. dr. Muhammad Hussein Gasem, PhD, SpPD-KPTI - **Phone:** +62248446757 - **Role:** CONTACT ***Contact 2:*** - **Name:** dr. Nur Farhanah Sp.PD, K-PTI, MSi.Med - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 560: University of Diponegoro/ Dr. Kariadi Hospital **State:** Central Of Java **Status:** NOT_YET_RECRUITING **Zip:** 50244 **Location 3:** **City:** Jakarta **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Prof. Dr. Pratiwi Sudarmono, PhD, SpMK (K) - **Phone:** +62 21 315 59 96 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr. dr. Evy Yunihastuti, Sp.PD-KAI - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 530: University of Indonesia/ Dr. Cipto Mangunkusumo Hospital **State:** DKI Jakarta **Status:** NOT_YET_RECRUITING **Zip:** 10430 **Location 4:** **City:** Jakarta **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dr. Vivi Lisdawati, Msi,Apt - **Phone:** +62216506559 - **Phone Ext:** 3119 - **Role:** CONTACT ***Contact 2:*** - **Name:** dr. Adria Rusli, Sp.P - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 540: Penyakit Infeksi Sulianti Saroso Hospital **State:** DKI Jakarta **Status:** NOT_YET_RECRUITING **Zip:** 14340 **Location 5:** **City:** Jakarta **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dr. dr. Erlina Burhan, SpP(K), MSc - **Phone:** +628161628471 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr. dr. Erlina Burhan, SpP(K), MSc - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 590: Persahabatan Hospital **State:** DKI Jakarta **Status:** NOT_YET_RECRUITING **Zip:** 14340 **Location 6:** **City:** Samarinda **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dr. dr. Carta Agrawanto Gunawan, Sp.PD, K-PTI - **Phone:** +62 541738118 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Dr. dr. Sunarto Ang, M.Sc - **Phone:** +62 541738118 - **Role:** CONTACT **Country:** Indonesia **Facility:** Site 660 RSUD Abdul Wahab Sjahranie **State:** East Kalimantan **Status:** NOT_YET_RECRUITING **Zip:** 75123 **Location 7:** **City:** Maumere **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** dr. Asep Purnama, Sp.PD - **Phone:** (0382) 2426133 - **Role:** CONTACT ***Contact 2:*** - **Name:** dr. Asep Purnama, Sp.PD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 700 - RSUD Dr.TC Hillers **State:** East Nusa Tenggara **Status:** NOT_YET_RECRUITING **Zip:** 86113 **Location 8:** **City:** Surabaya **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Prof. Dr.Usman Hadi SpPD-KPTI - **Phone:** +631 5035975 - **Role:** CONTACT ***Contact 2:*** - **Name:** Prof. Dr.Usman Hadi SpPD, KPT - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 570: University of Airlangga/ Dr. Soetomo Hospital **State:** East Of Java **Status:** NOT_YET_RECRUITING **Zip:** 60286 **Location 9:** **City:** Medan **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** dr. Bambang Prabowo, MARS - **Phone:** (+6261) 8360143 - **Role:** CONTACT ***Contact 2:*** - **Name:** dr. Tambar Kembaren SpPD, K-PTI - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 600 : Adam Malik Hospital **State:** North Sumatra **Status:** NOT_YET_RECRUITING **Zip:** 20136 **Location 10:** **City:** Jayapura **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dr I Made Gede Darmaja, SpPD FINASIM - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr I Made Gede Darmaja, SpPD FINASIM - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 690 - RSUD Abepura **State:** Papua **Status:** NOT_YET_RECRUITING **Zip:** 99351 **Location 11:** **City:** Batam **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dr. Bratasena, Sp.PD, M.Ked - **Phone:** (0778) 454044 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr. Bratasena, Sp.PD, M.Ked - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 650: Budi Kemuliaan Hospital **State:** Riau Islands **Status:** NOT_YET_RECRUITING **Location 12:** **City:** Banjarmasin **Contacts:** ***Contact 1:*** - **Name:** dr. Anna Martiana Afida, Sp.PK,MPH - **Phone:** +62 511 6710000 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr. Hj. Wiwit Agung SNC, SPPD.K-Ger - **Phone:** +62 511 6710000 - **Role:** CONTACT ***Contact 3:*** - **Name:** Dr. Hj. Wiwit Agung SNC, SPPD.K-Ger - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 630: M. Ansari Saleh Hospital **State:** South Kalimantan **Status:** NOT_YET_RECRUITING **Zip:** 70125 **Location 13:** **City:** Bandung **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** dr. Bachti Alisjahbana, PhD, SpPD-KPTI - **Phone:** +62222030776 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr. Rudi Wisaksana Sp.PD-KPTI.,Ph.D - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 510: University of Padjajaran/ Dr. Hasan Sadikin Hospital **State:** West Java **Status:** NOT_YET_RECRUITING **Zip:** 40161 **Location 14:** **City:** Tangerang **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** dr. Dewi Lokida, SpPK - **Phone:** +62215523507 - **Role:** CONTACT ***Contact 2:*** - **Name:** dr. I Gede Rai Kosa, SpPD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** dr. Arif Budiman, SpA - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** dr. Chakrawati Hayuningsih, SpPK - **Role:** SUB_INVESTIGATOR **Country:** Indonesia **Facility:** Site 610 : RSU Kabupaten Tangerang **State:** West Java **Status:** RECRUITING **Zip:** 15111 **Location 15:** **City:** Pontianak **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** dr. Ivan Lumban Toruan, Sp.PD - **Phone:** (0561)737701 - **Role:** CONTACT ***Contact 2:*** - **Name:** dr. Ivan Lumban Toruan, Sp.PD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 680 - RSUD dr Soedarso **State:** West Kalimantan **Status:** NOT_YET_RECRUITING **Zip:** 78111 **Location 16:** **City:** Banda Aceh **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dr. dr. Kurnia Fitri Jamil, M.Kes., Sp.PD-KPTI - **Phone:** (0651) 22616 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr. dr. Kurnia Fitri Jamil, M.Kes., Sp.PD-KPTI - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 670 - RSUD Dr. Zainoel Abidin **Status:** NOT_YET_RECRUITING **Zip:** 24415 **Location 17:** **City:** Jakarta **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Prof. dr. Emiliana Tjitra, Msc, PhD - **Phone:** (021) 3904441 - **Role:** CONTACT ***Contact 2:*** - **Name:** dr. Emon Winardi Danudirgo, SpPD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 640: St. Carolus Hospital **Status:** NOT_YET_RECRUITING **Zip:** 10440 **Location 18:** **City:** Makassar **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Prof. Dr. Mansyur Arif, PhD, SpPK (K) - **Phone:** +6411-582678 - **Role:** CONTACT ***Contact 2:*** - **Name:** dr. Sudirman Katu SpPD, K-PTI - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 550: University of Hassanudin/ Dr. Wahidin Sudirohusodo Hospital **Status:** NOT_YET_RECRUITING **Zip:** 90245 **Location 19:** **City:** Yogyakarta **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** dr. Abu Tholib Aman, MSc, PhD, SpMK(K) - **Phone:** +6274560300 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dr. Yanri Subronto PhD, Sp.PD, FINASIM - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Indonesia **Facility:** Site 580: University of Gadjah Mada/ Dr. Sardjito Hospital **Status:** NOT_YET_RECRUITING **Zip:** 55284 #### Overall Officials **Official 1:** **Affiliation:** National Institute of Health Research and Development, Ministry of Health Republic of Indonesia **Name:** Dr. Muhammad Karyana, MPH **Role:** PRINCIPAL_INVESTIGATOR ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2023-02-26 - Date Unknown: Unknown #### Event: RESET - Date: 2023-12-06 - Date Unknown: Unknown ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infectious Disease - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infectious Disease - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2023-02-26 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2023-02-26 - Reset Date: 2023-12-06 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - MCP Release N: Unknown - Release Date: 2023-12-21 - Reset Date: Unknown - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT02009579 **Brief Title:** ENGOT-cx1/BGOG-cx1: 3 Weekly Carboplatin/Paclitaxel With or Without Nintedanib in Cervix Cancer **Official Title:** BGOG-cx1/ENGOT-cx1: "Randomized Double-blind Phase II Study Comparing 3-weekly Carboplatin + Paclitaxel With or Without Concomitant and Maintenance Nintedanib (NINTEDANIB) in Advanced or Recurrent Cervical Carcinoma." #### Organization Study ID Info **ID:** BGOG-cx1/ENGOT-cx1 #### Organization **Class:** OTHER **Full Name:** Belgian Gynaecological Oncology Group ### Status Module #### Completion Date **Date:** 2023-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-27 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-26 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2021-01 **Type:** ACTUAL #### Start Date **Date:** 2014-03 **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2013-12-12 **Type:** ESTIMATED **Study First Submit Date:** 2013-10-24 **Study First Submit QC Date:** 2013-12-09 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Grupo Español de Investigación en Cáncer de Ovario **Class:** OTHER **Name:** Mario Negri Gynecologic Oncology group (MaNGO) **Class:** UNKNOWN **Name:** Multicenter Italian Trials in Ovarian Cancer (MITO) **Class:** OTHER **Name:** North Eastern German Society of Gynaecological Oncology #### Lead Sponsor **Class:** OTHER **Name:** Belgian Gynaecological Oncology Group #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Indication: Treatment of subjects with advanced (FIGO stage IVB) or recurrent cervical cancer, prior radiochemotherapy or neo-adjuvant chemotherapy is allowed. Study design: This is a phase II randomized, double blind and placebo controlled trial evaluating the efficacy of Nintedanib/placebo in combination with the standard carboplatin and paclitaxel followed by Nintedanib/placebo maintenance in the treatment of patients with advanced or recurrent cervical cancer. A total of 120 patients will be randomized between the experimental and control arm in a 1:1 ratio. Randomization will be stratified for 1previous chemotherapy for metastatic disease (yes/no) and 2disease status (Stage IVB primary versus recurrent disease). Experimental arm: Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and Nintedanib 200 mg BID followed by Nintedanib maintenance until progression or for a total maximum duration of 120 weeks. Control arm: Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and placebo 200 mg BID followed by placebo maintenance until progression or for a total maximum duration of 120 weeks. Subjects without evidence of disease progression after completion or discontinuation of the study treatment will be followed until radiographic disease progression, withdrawal of consent or death. ### Conditions Module **Conditions:** - Uterine Cervical Neoplasms **Keywords:** - Uterine Cervical Cancer - Paclitaxel - Carboplatin - Nintedanib ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 120 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Nintedanib/vargatef **Intervention Names:** - Drug: Nintedanib **Label:** Experimental arm **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Placebo **Intervention Names:** - Drug: Placebo **Label:** Comparator arm **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental arm **Description:** Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and Nintedanib 200 mg BID followed by Nintedanib maintenance until progression or for a total maximum duration of 120 weeks. **Name:** Nintedanib **Other Names:** - Vargatef **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Comparator arm **Description:** Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and placebo 200 mg BID followed by placebo maintenance until progression or for a total maximum duration of 120 weeks. **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Primary objective: The purpose of this trial is to determine if chemotherapy (carboplatin/paclitaxel) plus Nintedanib (BIBF 1120) can improve progression free survival compared to chemotherapy (carboplatin/paclitaxel) plus placebo in patients with advanced or recurrent cervical cancer. **Measure:** Progression free survival **Time Frame:** 1.5 years after LPI #### Secondary Outcomes **Description:** Secondary objectives: To evaluate the safety and toxicity reported for of the combination regimen **Measure:** Safety and toxicity **Time Frame:** 5 years after LPI **Description:** To evaluate the response rate according to RECIST 1.1 **Measure:** Overall survival **Time Frame:** 5 years after LPI **Description:** To explore the effect of Nintedanib on patient reported health status as measured by EORTC-QOL-Cx 24 and EORTCQLQ-C30 questionnaires **Measure:** Patient health status **Time Frame:** 5 years after LPI **Description:** To evaluate the overall survival **Measure:** Overall survival **Time Frame:** 5 years after LPI ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Female subjects more than 18 years of age * Histologically or cytologically confirmed advanced (\[FIGO\] stage IVB), or recurrent/persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix will be eligible. * Prior treatment with angiogenesis inhibitors is allowed * Up to one prior line of chemotherapy for metastatic cervical cancer is allowed. * Treatment of primary disease with concomitant cisplatinum chemotherapy during radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease. * Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery is allowed and does not count as a line of chemotherapy for metastatic disease. * Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiochemotherapy is allowed and does not count as a line of chemotherapy for metastatic disease. * Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease. * Life expectancy at least 3 months. * ECOG Performance status score of 0 or 1 * At least one measurable lesion according to RECIST 1.1 criteria * Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation Exclusion Criteria: * Known hypersensitivity to the trial drugs or to their excipients (including peanut or soya). * Brain or leptomeningeal metastases. * Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels. * Tumor infiltrating the mucosa of the bowel or bladder, or known fistulas between the tumor and the gastrointestinal or urinary tract. * Radiographic evidence of cavitary or necrotic tumours * Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial. * Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid \<325 mg per day). * Major injuries within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period. * History of clinically significant haemorrhagic or thromboembolic event in the past 6 months. * Known inherited predisposition to bleeding or thrombosis. * Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina within the past 6 months, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure \> NYHA II, serious cardiac arrhythmia, pericardial effusion). * History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months. * Abnormal renal, liver or bone marrow function defined as: * Proteinuria CTCAE grade 2 or greater * Creatinin \> 2 ULN or GFR \< 30 ml/min * Hepatic function: total bilirubin outside of normal limits; ALT or AST \> 1.5 ULN in pts without liver metastasis. For Pts with liver metastases: total bilirubin outside of normal limits, ALT or AST \> 2.5 ULN * Coagulation parameters: International normalised ratio (INR) \> 2, prothrombin time (PT) and partial thromboplastin time (PTT) \> 50% of deviation of institutional ULN * Absolute neutrophil count ( ANC) \< 1500/µl, platelets \< 100000/µl, haemoglobin \< 9.0 g/dl * Other malignancies within the past 3 years or other malignancy with recurrence in the past 3 years or with high risk of recurrence in the first year. In exception to this rule, the following malignancies may be included: non-melanomatous skin cancer (if adequately treated) , any premalignant (e.g. in situ) carcinoma, or basocellular carcinoma. * Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy. * Active or chronic hepatitis C and/or B infection or known HIV infection (based on medical file, only for Italy a mandatory screening test for HIV should be performed for all patients who did not have this test within the last 3 months before the study treatment start). * Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug. * Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study. * Patients of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner or sexual abstinence for participating females) during the trial and for at least three months after end of active therapy. * Pregnancy or breast feeding, female patients must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment, if applicable. * Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule. * Active alcohol or drug abuse. **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bruxelles **Country:** Belgium **Facility:** CHU Saint-Pierre **Location 2:** **City:** Bruxelles **Country:** Belgium **Facility:** Institut Jules Bordet **Location 3:** **City:** Charleroi **Country:** Belgium **Facility:** Grand Hopital de Charleroi **Location 4:** **City:** Edegem **Country:** Belgium **Facility:** UZ Antwerpen **Location 5:** **City:** Kortrijk **Country:** Belgium **Facility:** AZ Groeninge **Location 6:** **City:** Leuven **Country:** Belgium **Facility:** UZ Leuven **Zip:** 3000 **Location 7:** **City:** Liege **Country:** Belgium **Facility:** CHR Citadelle **Location 8:** **City:** Liège **Country:** Belgium **Facility:** CHU de Liège **Zip:** 4000 **Location 9:** **City:** Namur **Country:** Belgium **Facility:** Clinique et maternite St. Elisabeth **Location 10:** **City:** Yvoir **Country:** Belgium **Facility:** Cliniques Universitaires mont godinne **Location 11:** **City:** Berlin **Country:** Germany **Facility:** Charité Med Uni Berlin **Location 12:** **City:** Dresden **Country:** Germany **Facility:** Universitätsklinikum Carl Gustav Carus Dresden **Location 13:** **City:** Essen **Country:** Germany **Facility:** Kliniken Essen Mitte **Location 14:** **City:** Gottingen **Country:** Germany **Facility:** Georg-August University Göttingen **Location 15:** **City:** Greifswald **Country:** Germany **Facility:** Medical University Greifswald **Location 16:** **City:** Tubingen **Country:** Germany **Facility:** University Tübingen **Location 17:** **City:** Aviano **Country:** Italy **Facility:** Centro Riferimento Oncologico **Location 18:** **City:** Brescia **Country:** Italy **Facility:** Spedali Civili **Location 19:** **City:** Catania **Country:** Italy **Facility:** Azienda Ospedaliera Cannizzaro **Location 20:** **City:** Milano **Country:** Italy **Facility:** National Cancer Institute **Location 21:** **City:** Naples **Country:** Italy **Facility:** Istituto Nazionale Tumori-Pascale Naples **Location 22:** **City:** Padova **Country:** Italy **Facility:** Padova Istituti Oncologico Veneto **Location 23:** **City:** Pisa **Country:** Italy **Facility:** University Pisa **Location 24:** **City:** Reggio Emilia **Country:** Italy **Facility:** AUSL Reggio Emilia **Location 25:** **City:** Rome **Country:** Italy **Facility:** Poloclinico A Gemelli **Location 26:** **City:** Torino **Country:** Italy **Facility:** Mauriziano -Torino **Location 27:** **City:** Torino **Country:** Italy **Facility:** S. Anna Torino **Location 28:** **City:** Córdoba **Country:** Spain **Facility:** Hospital Provincial Reina Sofia **Zip:** 14004 **Location 29:** **City:** Madrid **Country:** Spain **Facility:** H. Ramón y Cajal **Zip:** 28034 **Location 30:** **City:** Madrid **Country:** Spain **Facility:** Hospital Clinico San Carlos **Zip:** 28040 **Location 31:** **City:** Murcia **Country:** Spain **Facility:** Hospital Universitario Morales Meseguer **Zip:** 30008 **Location 32:** **City:** Palma Mallorca **Country:** Spain **Facility:** Hospital Son Llatzer **Zip:** 07198 ### References Module #### See Also Links **Label:** ENGOT website **URL:** http://www.esgo.org/engot/Pages/AboutENGOT.aspx ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014594 - Term: Uterine Neoplasms - ID: D000005833 - Term: Genital Neoplasms, Female - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000002577 - Term: Uterine Cervical Diseases - ID: D000014591 - Term: Uterine Diseases - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5830 - Name: Uterine Cervical Neoplasms - Relevance: HIGH - As Found: Uterine Cervical Neoplasms - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M17342 - Name: Uterine Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8945 - Name: Genital Neoplasms, Female - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5825 - Name: Uterine Cervical Diseases - Relevance: LOW - As Found: Unknown - ID: M17339 - Name: Uterine Diseases - Relevance: LOW - As Found: Unknown - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002583 - Term: Uterine Cervical Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M19537 - Name: Paclitaxel - Relevance: LOW - As Found: Unknown - ID: M231 - Name: Albumin-Bound Paclitaxel - Relevance: LOW - As Found: Unknown - ID: M18650 - Name: Carboplatin - Relevance: LOW - As Found: Unknown - ID: M272925 - Name: Nintedanib - Relevance: HIGH - As Found: Group I - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000530716 - Term: Nintedanib ### Misc Info Module - Version Holder: 2024-05-24
## Protocol Section ### Identification Module **NCT ID:** NCT05432479 **Acronym:** PIXAR **Brief Title:** Study to Evaluate the Efficacy of a Probiotic in Infantile Colic Symptoms Relief **Official Title:** A Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Efficacy of a Probiotic in Infantile Colic Symptoms Relief #### Organization Study ID Info **ID:** PCTB202010 #### Organization **Class:** INDUSTRY **Full Name:** The Archer-Daniels-Midland Company ### Status Module #### Completion Date **Date:** 2023-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2022-06-30 **Type:** ACTUAL **Last Update Submit Date:** 2022-06-27 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2023-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-07 **Type:** ESTIMATED **Status Verified Date:** 2022-05 #### Study First Post Date **Date:** 2022-06-27 **Type:** ACTUAL **Study First Submit Date:** 2022-06-21 **Study First Submit QC Date:** 2022-06-21 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Atlantia Food Clinical Trials #### Lead Sponsor **Class:** INDUSTRY **Name:** The Archer-Daniels-Midland Company #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study evaluates the efficacy of single strain probiotic administered in a form of a sachet in the treatment of infant colic in infants 3-12 weeks old. ### Conditions Module **Conditions:** - Infantile Colic **Keywords:** - probiotic - Bifidobacterium ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 80 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Arm receiving investigation product (probiotic) **Intervention Names:** - Dietary Supplement: Probiotic **Label:** Active **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Arm receiving placebo **Intervention Names:** - Dietary Supplement: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Active **Description:** Single strain probiotic in a form of a sachets with a daily dose of 1.0E+9 Colony Forming Unit (CFU) per day for 4 weeks **Name:** Probiotic **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo **Name:** Placebo **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Other Outcomes **Description:** Change in maternal QoL using WHO QOL/BREF (improvement marked by increase in the total score) **Measure:** Change in maternal quality of life and mental health **Time Frame:** Day 0, Day 28 **Description:** Change in maternal QoL using MMPP/QoL (improvement marked by increase in the total score) **Measure:** Change in maternal quality of life and mental health **Time Frame:** Day 0, Day 28 #### Primary Outcomes **Description:** eDiary parent reported cry and fuss time **Measure:** Change in cry and fuss time **Time Frame:** Day 0 , Day 28 #### Secondary Outcomes **Description:** Reduction of cry and fuss time (parent reported) greater than 90% comparing to baseline **Measure:** Resolution of colic symptoms **Time Frame:** Day 0, Day 28 **Description:** eDiary parent reported cry and fuss bouts **Measure:** Change in cry and fuss time bouts **Time Frame:** Day 0, Day 28 **Description:** eDiary parent reported sleep time **Measure:** Change in sleeping time **Time Frame:** Day 0 Day 28 **Description:** Change in the proportion of participants needing to use rescue medications between the study arms **Measure:** Change in the use of rescue medications **Time Frame:** Day 0, Day 28 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Gestational age of minimum 37 weeks. * Birthweight of minimum 2500 g (5.5 lb.). * Age of greater than 3 weeks and less than 12 weeks at enrolment. * Confirmed Infantile colic defined as: parental report of crying and/or fussing ≥3 hours/day for ≥3 days/week, confirmed prior to enrolment with an infant behaviour diary recording \>3 hours of crying in a 24-hour period (eDiary App completed daily during run-in period \& for duration of study). * Participant Informed Consent form signed by parent or legal guardian. * Infant is considered healthy following physical exam. * Parents/Caregivers are willing to comply with the trial procedures, and the mother of the infant can attend all three trial visits Exclusion Criteria: * Use of antibiotics by the infant within 2-weeks prior to the screening visit or during the run-in period of the trial. * Use of probiotic supplements from child's birth to enrolment (this includes infant formulas containing probiotics). * Need for hospitalization (defined as readmission to a hospital ward after initial discharge following delivery). * Congenital disorders that, in the opinion of the investigator, would impact the gastrointestinal tract. * Failure to thrive. * Known lactose or gluten intolerance. * Known allergy to cow's milk proteins, fish, or any of the substances of the trial product or placebo. * Known other causes for abdominal pain (e.g., pyloric stenosis). * Participation in any other interventional clinical study. * Immuno-compromised participant or participant with other severe chronic disorder. * Use of probiotic supplements by breastfeeding mother from child's birth to enrolment. * Use of antibiotics by breastfeeding mother within 2-weeks prior to the screening visit or during the run-in period of the trial. * Any Participant/Parent/Caregiver who is an employee of the investigational site or an Atlantia Clinical Trials employee or their close family member or a member of their household. **Maximum Age:** 12 Weeks **Minimum Age:** 3 Weeks **Sex:** ALL **Standard Ages:** - CHILD ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007232 - Term: Infant, Newborn, Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M6313 - Name: Colic - Relevance: HIGH - As Found: Infantile Colic - ID: M10276 - Name: Infant, Newborn, Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003085 - Term: Colic ### Intervention Browse Module - Browse Branches - Abbrev: Ot - Name: Other Dietary Supplements - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T367 - Name: Bifidobacterium - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24