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## Protocol Section ### Identification Module **NCT ID:** NCT06204679 **Brief Title:** Pharmacokinetics of Fixed-Dose Combination Tablet of Bemnifosbuvir and Ruzasvir **Official Title:** A Phase 1, Open-Label Study to Assess Comparative Bioavailability and Effect of Food on a Prototype Fixed-Dose Combination of Bemnifosbuvir and Ruzasvir Versus Individual Dosage Forms Taken Concomitantly in Healthy Adult Subjects #### Organization Study ID Info **ID:** AT-01B-005 #### Organization **Class:** INDUSTRY **Full Name:** Atea Pharmaceuticals, Inc. ### Status Module #### Completion Date **Date:** 2024-02-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-12 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-11 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-02-12 **Type:** ESTIMATED #### Start Date **Date:** 2023-12-14 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2024-01-12 **Type:** ACTUAL **Study First Submit Date:** 2024-01-02 **Study First Submit QC Date:** 2024-01-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Atea Pharmaceuticals, Inc. #### 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 study will assess comparative bioavailability and effect of food on a prototype fixed-dose combination (FDC) of Bemnifosbuvir (BEM) and Ruzasvir (RZR) in healthy subjects ### Conditions Module **Conditions:** - Healthy Volunteer Study ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Day 1, Day 7, Day 13 **Intervention Names:** - Drug: Bemnifosbuvir (BEM)/Ruzasvir (RZR) FDC under fasting conditions **Label:** FDC Fasting **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Day 1, Day 7, Day 13 **Intervention Names:** - Drug: Bemnifosbuvir (BEM)/Ruzasvir (RZR) FDC under fed conditions **Label:** FDC Fed **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Day 1, Day 7, Day 13 **Intervention Names:** - Drug: Bemnifosbuvir (BEM) and Ruzasvir (RZR) as reference formulation under fasting conditions **Label:** Reference Fasting **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - FDC Fasting **Description:** A Fixed-Dose Combination of Bemnifosbuvir (BEM) and Ruzasvir (RZR) **Name:** Bemnifosbuvir (BEM)/Ruzasvir (RZR) FDC under fasting conditions **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - FDC Fed **Description:** A Fixed-Dose Combination of Bemnifosbuvir (BEM) and Ruzasvir (RZR) **Name:** Bemnifosbuvir (BEM)/Ruzasvir (RZR) FDC under fed conditions **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Reference Fasting **Description:** Bemnifosbuvir (BEM) and Ruzasvir (RZR) as separate formulations **Name:** Bemnifosbuvir (BEM) and Ruzasvir (RZR) as reference formulation under fasting conditions **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Maximum plasma concentration (Cmax) **Measure:** Pharmacokinetics (PK) of FDC compared to reference:(Cmax) **Time Frame:** Day 1, Day 7, Day 13 **Description:** Area under the plasma concentration-time curve (AUC) **Measure:** Pharmacokinetics (PK) of FDC compared to reference:(AUC) **Time Frame:** Day 1, Day 7, Day 13 **Description:** Maximum plasma concentration (Cmax) **Measure:** Food effect of Fixed Dose Combination of Bemnifosbuvir (BEM)/Ruzasvir (RZR):(Cmax) **Time Frame:** Day 1, Day 7, Day 13 **Description:** Area under the plasma concentration-time curve (AUC) **Measure:** Food effect of Fixed Dose Combination of Bemnifosbuvir (BEM)/Ruzasvir (RZR):(AUC) **Time Frame:** Day 1, Day 7, Day 13 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Must agree to use two methods of birth control from Screening through 90 days after administration of the last dose of study drug. * Minimum body weight of 50 kg and body mass index (BMI) of 18-30 kg/m2. * Willing to comply with the study requirements and to provide written informed consent. Exclusion Criteria: * Infected with hepatitis B virus, hepatitis C virus, HIV or SARS-CoV-2. * Abuse of alcohol or drugs. * Use of other investigational drugs within 28 days of dosing. * Concomitant use of prescription medications, or systemic over-the-counter medications. * Other clinically significant medical conditions or laboratory abnormalities. **Healthy Volunteers:** True **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:** Atea Study Clinical Trials Administrator **Phone:** 888-481-1607 **Role:** CONTACT #### Locations **Location 1:** **City:** Cypress **Country:** United States **Facility:** Atea Study Site **State:** California **Status:** RECRUITING **Zip:** 90630 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000998 - Term: Antiviral 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: M263854 - Name: Ruzasvir - Relevance: HIGH - As Found: Mood stabilizer - 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: C000621654 - Term: Ruzasvir ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01054079 **Brief Title:** Cinacalcet Hydrochloride in Treating Men With Recurrent Prostate Cancer **Official Title:** A Phase II Trial to Assess the Effect of Cinacalcet Hydrochloride on PSA Levels in Patients With Biochemically Recurrent Prostate Cancer After Failed Definitive Local Therapy #### Organization Study ID Info **ID:** IRB00009741 #### Organization **Class:** OTHER **Full Name:** Wake Forest University Health Sciences #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2009-01514 **Type:** REGISTRY **Domain:** Wake Forest University Health Sciences **ID:** CCCWFU 98309 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2014-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-07-05 **Type:** ACTUAL **Last Update Submit Date:** 2018-07-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2015-10-29 **Type:** ESTIMATED **Results First Submit Date:** 2015-08-14 **Results First Submit QC Date:** 2015-09-29 #### Start Date **Date:** 2011-09 **Status Verified Date:** 2018-07 #### Study First Post Date **Date:** 2010-01-22 **Type:** ESTIMATED **Study First Submit Date:** 2010-01-21 **Study First Submit QC Date:** 2010-01-21 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### 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:** False ### Description Module **Brief Summary:** This phase II trial is studying how well cinacalcet hydrochloride works in treating men with recurrent prostate cancer. Cinacalcet hydrochloride may be effective in lowering prostate-specific antigen (PSA) levels in patients with recurrent prostate cancer that has not responded to previous treatment **Detailed Description:** PRIMARY OBJECTIVES: I. To test the hypothesis that once-daily treatment with 30 mg of cinacalcet hydrochloride (Sensipar) will reduce the rate of rise of serum prostate-specific antigen (PSA) compared to pre-treatment PSA values in subjects with biochemically recurrent prostate cancer after failed definitive local therapy. OUTLINE: Patients receive cinacalcet hydrochloride orally (PO) once daily (QD) for 20 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks. ### Conditions Module **Conditions:** - Adenocarcinoma of the Prostate - Recurrent Prostate Cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. **Intervention Names:** - Other: laboratory biomarker analysis - Procedure: quality-of-life assessment - Other: questionnaire administration - Drug: cinacalcet hydrochloride **Label:** Treatment (cinacalcet hydrochloride) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment (cinacalcet hydrochloride) **Description:** Correlative study **Name:** laboratory biomarker analysis **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Treatment (cinacalcet hydrochloride) **Description:** Ancillary study **Name:** quality-of-life assessment **Other Names:** - quality of life assessment **Type:** PROCEDURE #### Intervention 3 **Arm Group Labels:** - Treatment (cinacalcet hydrochloride) **Description:** Ancillary study **Name:** questionnaire administration **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Treatment (cinacalcet hydrochloride) **Description:** Given PO **Name:** cinacalcet hydrochloride **Other Names:** - Mimpara - Sensipar **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The difference of post treatment and pre-enrollment PSA.For those with multiple PSA measures post we use the median of those measures to estimate the participant's post PSA level. **Measure:** Rate of Rise of Serum PSA **Time Frame:** 24 weeks #### Secondary Outcomes **Description:** The Brief Male Sexual Inventory is an 11 question assessment including subscales: sex drive, erections, ejaculation. The scores are totaled to produce an overall score with a range of 1-45, with higher score indicating worse outcomes. **Measure:** Change in Quality of Life (QOL) as Assessed by the Brief Male Sexual Inventory **Time Frame:** Up to 20 weeks **Description:** The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Epic produces two scores, one for function (5 items) and the other for bother (6 items). The response for each item is standardized to a 0 to 100 scale. For both scales, higher scores indicate worse outcomes. **Measure:** Change in Hormonal Assessment Scale From Expanded Prostate Cancer Index Composite (EPIC) **Time Frame:** up to 20 weeks **Description:** The FACT-P is a multidimensional, self-report QoL instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score. All subscale items are summed to a total. The score range is 0-156. Higher scores represent better quality of life. **Measure:** Change in Functional Assessment of Cancer Therapy-Prostate (FACT-P) **Time Frame:** up to 20 weeks **Description:** The detectable difference is estimated using a paired t-test approach. The lab measure will also be analyzed longitudinally using all measures with a mixed model approach adjusting for individual covariates. **Measure:** Change in Total and Free Testosterone **Time Frame:** Up to 20 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate * For patients who have recurrent disease following surgery as first line therapy ("surgical failures") * PSA requirement is 0.2 ng/ml or above * For patients who have recurrent disease following radiation as first line therapy, the eligibility follows the "Phoenix criteria", that is, a rise of 2 ng/mL over the PSA nadir * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Granulocytes \>= 1000/uL * Serum creatinine =\< 2.0 mg/dl * Total serum calcium \> 9.0 and \< 10.5 mg/dl * Total bilirubin =\< 2.0 mg/dl * Platelet count \>=100,000/uL * Hemoglobin (Hgb) \>= 9 g/dL * Total testosterone \>= 50 ng/dL * Ability to understand and the willingness to sign a written informed consent document (either directly or via a legally authorized representative) Exclusion Criteria: * Serious medical illness which would limit survival to less than 3 months * Active, uncontrolled bacterial, viral or fungal infection * Hemorrhagic disorder * Any radiographic evidence of metastatic disease including positive bone scan or computed tomography (CT) abdomen/pelvis * History of hypocalcemia or seizure disorder * Patients with known hypersensitivity to any of the components of cinacalcet (cinacalcet hydrochloride) **Minimum Age:** 18 Years **Sex:** MALE **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 #### Overall Officials **Official 1:** **Affiliation:** Wake Forest University Health Sciences **Name:** K.C. Balaji, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - 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 ### 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: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M14335 - Name: Prostatic Neoplasms - Relevance: HIGH - As Found: Prostate Cancer - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrent - ID: M22700 - Name: Disease Attributes - 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 ### Condition Browse Module - Meshes - ID: D000011471 - Term: Prostatic Neoplasms - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000077264 - Term: Calcium-Regulating Hormones and Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000057966 - Term: Calcimimetic Agents - ID: D000006727 - Term: Hormone Antagonists - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: BDCA - Name: Bone Density Conservation Agents ### Intervention Browse Module - Browse Leaves - ID: M418 - Name: Cinacalcet - Relevance: HIGH - As Found: FGFR - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M5381 - Name: Calcium - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069449 - Term: Cinacalcet ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Treatment (Cinacalcet Hydrochloride) **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Correlative study quality-of-life assessment: Ancillary study questionnaire administration: Ancillary study cinacalcet hydrochloride: Given PO **ID:** EG000 **Other Num Affected:** 16 **Other Num at Risk:** 20 **Serious Number Affected:** 3 **Serious Number At Risk:** 20 **Title:** Treatment (Cinacalcet Hydrochloride) **Frequency Threshold:** 0 #### Other Events **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Diarrhea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Neuropathy: sensory **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) **Term:** hypocalcemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (3.0) **Term:** hyponatremia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (3.0) **Term:** Pruritus/itching **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Joint **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** hypertriglyceridemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Muscle **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** hypocalcemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (3.0) #### Serious Events **Term:** Cardiac ischemia/infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** hypocalcemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Hypoxia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Atrial fibrillation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Lymphopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Pulmonary hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Cardiac troponin T increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 20 **Units:** Participants ### Group **ID:** BG000 **Title:** Treatment (Cinacalcet Hydrochloride) **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Correlative study quality-of-life assessment: Ancillary study questionnaire administration: Ancillary study cinacalcet hydrochloride: Given PO ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 12 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 8 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 7.1 **Value:** 66.6 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 20 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 20 **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 ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Comprehensive Cancer Center of Wake Forest University **Phone:** 336-618-2272 **Title:** Dr. K.C. Balaji ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.01 - **Spread:** - **Upper Limit:** 0.17 - **Value:** 0.0825 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.7 - **Upper Limit:** - **Value:** 23.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** 21.8 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.8 - **Upper Limit:** - **Value:** 86 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.1 - **Upper Limit:** - **Value:** 88 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** 92.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** 91.9 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.4 - **Upper Limit:** - **Value:** 122.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.1 - **Upper Limit:** - **Value:** 124.1 **Title:** #### Outcome Measure 5 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The difference of post treatment and pre-enrollment PSA.For those with multiple PSA measures post we use the median of those measures to estimate the participant's post PSA level. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** 24 weeks **Title:** Rate of Rise of Serum PSA **Type:** PRIMARY **Unit of Measure:** Nanograms Per Milliliter ##### Group **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Correlative study quality-of-life assessment: Ancillary study questionnaire administration: Ancillary study cinacalcet hydrochloride: Given PO **ID:** OG000 **Title:** Treatment (Cinacalcet Hydrochloride) #### Outcome Measure 2 **Description:** The Brief Male Sexual Inventory is an 11 question assessment including subscales: sex drive, erections, ejaculation. The scores are totaled to produce an overall score with a range of 1-45, with higher score indicating worse outcomes. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Up to 20 weeks **Title:** Change in Quality of Life (QOL) as Assessed by the Brief Male Sexual Inventory **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Correlative study quality-of-life assessment: Ancillary study questionnaire administration: Ancillary study cinacalcet hydrochloride: Given PO **ID:** OG000 **Title:** Treatment (Cinacalcet Hydrochloride) #### Outcome Measure 3 **Description:** The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Epic produces two scores, one for function (5 items) and the other for bother (6 items). The response for each item is standardized to a 0 to 100 scale. For both scales, higher scores indicate worse outcomes. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** up to 20 weeks **Title:** Change in Hormonal Assessment Scale From Expanded Prostate Cancer Index Composite (EPIC) **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Correlative study quality-of-life assessment: Ancillary study questionnaire administration: Ancillary study cinacalcet hydrochloride: Given PO **ID:** OG000 **Title:** Treatment (Cinacalcet Hydrochloride) #### Outcome Measure 4 **Description:** The FACT-P is a multidimensional, self-report QoL instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score. All subscale items are summed to a total. The score range is 0-156. Higher scores represent better quality of life. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** up to 20 weeks **Title:** Change in Functional Assessment of Cancer Therapy-Prostate (FACT-P) **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Correlative study quality-of-life assessment: Ancillary study questionnaire administration: Ancillary study cinacalcet hydrochloride: Given PO **ID:** OG000 **Title:** Treatment (Cinacalcet Hydrochloride) #### Outcome Measure 5 **Description:** The detectable difference is estimated using a paired t-test approach. The lab measure will also be analyzed longitudinally using all measures with a mixed model approach adjusting for individual covariates. **Population Description:** No data collected **Reporting Status:** POSTED **Time Frame:** Up to 20 weeks **Title:** Change in Total and Free Testosterone **Type:** SECONDARY ##### Group **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Correlative study quality-of-life assessment: Ancillary study questionnaire administration: Ancillary study cinacalcet hydrochloride: Given PO **ID:** OG000 **Title:** Treatment (Cinacalcet Hydrochloride) ### Participant Flow Module #### Group **Description:** Patients receive cinacalcet hydrochloride PO QD for 20 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Correlative study quality-of-life assessment: Ancillary study questionnaire administration: Ancillary study cinacalcet hydrochloride: Given PO **ID:** FG000 **Title:** Treatment (Cinacalcet Hydrochloride) #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ##### Milestone **Type:** # Recieved Proper PSA Testing ###### Achievement **Group ID:** FG000 **Number of Subjects:** 10 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00123279 **Brief Title:** Intravitreal Microplasmin in Patients Undergoing Surgical Vitrectomy **Official Title:** A Dose-escalation Clinical Trial of Intravitreal Microplasmin in Patients Undergoing Surgical Vitrectomy for Vitreomacular Traction Maculopathy #### Organization Study ID Info **ID:** TG-MV-001 #### Organization **Class:** INDUSTRY **Full Name:** ThromboGenics ### Status Module #### Completion Date **Date:** 2008-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-04-07 **Type:** ESTIMATED **Last Update Submit Date:** 2014-04-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-02 **Type:** ACTUAL #### Start Date **Date:** 2004-12 **Status Verified Date:** 2014-04 #### Study First Post Date **Date:** 2005-07-22 **Type:** ESTIMATED **Study First Submit Date:** 2005-07-21 **Study First Submit QC Date:** 2005-07-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** ThromboGenics #### Responsible Party **Old Name Title:** Edith Van Dijkman **Old Organization:** ThromboGenics ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this trial is to evaluate the safety and preliminary efficacy of different doses and several exposure times of intravitreal microplasmin in the setting of pars plana vitrectomy for vitreomacular traction maculopathy. **Detailed Description:** Study drug will be administered in the mid-vitreous by injection. Patients will be enrolled into the cohorts in a sequential dose/time-escalating fashion. To ensure that enrolment is evenly balanced across eligible conditions, enrolment of any specific underlying disease type into any cohort will be capped at five (5) patients. ### Conditions Module **Conditions:** - Vitreomacular Traction Maculopathy - Eye Diseases **Keywords:** - diabetic macular edema - macular hole - vitreomacular traction syndrome ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Microplasmin **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Microplasmin **Label:** 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Intervention Names:** - Drug: Microplasmin **Label:** 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Intervention Names:** - Drug: Microplasmin **Label:** 4 **Type:** EXPERIMENTAL #### Arm Group 5 **Intervention Names:** - Drug: Microplasmin **Label:** 5 **Type:** EXPERIMENTAL #### Arm Group 6 **Intervention Names:** - Drug: Microplasmin **Label:** 6 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 - 2 - 3 - 4 - 5 - 6 **Description:** 25ug injected 1 hr prior to PPV, 24 hr and 7 days prior to PPV, 50ug injected 24 hr prior to PPV, 75ug injected 24 hr prior to PPV and 125ug injected 24 hr prior to PPV. **Name:** Microplasmin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Grade of Posterior Vitreous Detachment (PVD) preoperatively and release of vitreomacular traction **Time Frame:** Baseline, 1,2 and 3hr, 1, 3, 14, 28, 90 and 180 Days #### Secondary Outcomes **Measure:** The occurrence of any (serious) adverse event **Time Frame:** Throught-out the study ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with vitreomacular traction maculopathy for whom vitrectomy is indicated, according to the principal investigator, including: * Macular edema associated with vitreomacular traction (DME, VMTS); * Stage II-III macular hole of \< 6 months duration since symptom onset; * Demonstration of vitreomacular adhesion (based on preoperative optic coherence tomography \[OCT\]) in the study eye; * OCT - presence of posterior hyaloid membrane inserting on to the macula, but with some area of clear separation visible between the retina and the posterior hyaloid. Exclusion Criteria: * Evidence of fibrocellular proliferation characterized by whitish epimacular tissue (surface wrinkling is not an exclusion criterion). * Patients with vitreous hemorrhage which precludes either of the following: visualization of the posterior pole by visual inspection OR adequate assessment of the macula by either OCT and/or fluorescein angiogram in the study eye. * Patients with rhegmatogenous retinal detachment, proliferative vitreoretinopathy (PVR), or retinal degenerative changes in the study eye. * Patients with high myopia or aphakia in the study eye * Patients with history of rhegmatogenous retinal detachment in the fellow eye or family history of retinal detachment * Patients who are considered likely to require intraocular surgery in the study eye for any reason other than vitreomacular traction maculopathy/macular edema in the coming three months. * Patients who have had ocular surgery in the study eye in the prior three months. * Patients who have had a vitrectomy in the study eye at any time. * Patients with a history of uveitis or significant trauma in the study eye. * Patients who are currently being treated for glaucoma in the study eye. * Patients who have had laser photocoagulation treatment in the study eye in the previous 3 months. * Intravitreal injection of any drug in the study eye in the previous 6 months or during the study. * Patients who are pregnant or of child-bearing potential not utilizing a form of contraception acceptable to the investigator. * Patients who, in the investigator's view, will not complete all visits and investigations, including the exit visit at 6 months. * Patients who have participated in an investigational drug study within the past 30 days. * HgA1c \> 9%. * Patients with hypertension (either systolic blood pressure \[SBP\] \> 170 or diastolic blood pressure \[DBP\] \> 100 mm Hg). * Patients with a life-expectancy less than 6 months. * Patients who have previously participated in this trial. **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Leuven **Country:** Belgium **Facility:** University Hospital Gasthuisberg **Zip:** B-3000 **Location 2:** **City:** Amsterdam **Country:** Netherlands **Facility:** Academic Medical Center, University of Amsterdam **Zip:** 1105 AZ **Location 3:** **City:** Rotterdam **Country:** Netherlands **Facility:** Oogziekenhuis Rotterdam **Zip:** 3011 BH #### Overall Officials **Official 1:** **Affiliation:** Amsterdam UMC, location VUmc **Name:** Marc deSmet, Prof. Dr **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012162 - Term: Retinal Degeneration - ID: D000012164 - Term: Retinal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC11 - Name: Eye Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: HIGH - As Found: Eye Disease - ID: M11261 - Name: Macular Edema - Relevance: LOW - As Found: Unknown - ID: M7657 - Name: Edema - Relevance: LOW - As Found: Unknown - ID: M11260 - Name: Macular Degeneration - Relevance: HIGH - As Found: Maculopathy - ID: M14997 - Name: Retinal Degeneration - Relevance: LOW - As Found: Unknown - ID: M14999 - Name: Retinal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005128 - Term: Eye Diseases - ID: D000008268 - Term: Macular Degeneration ### Intervention Browse Module - Ancestors - ID: D000005343 - Term: Fibrinolytic Agents - ID: D000050299 - Term: Fibrin Modulating Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: FiAg - Name: Fibrinolytic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M13848 - Name: Plasminogen - Relevance: HIGH - As Found: Flower - ID: M8473 - Name: Fibrinolytic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000010958 - Term: Plasminogen ### Misc Info Module #### Removed Countries - Country: Germany - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05479279 **Brief Title:** Effectiveness of Neck Stabilization Training Program With Conventional Therapy in Management of Text Neck Syndrome **Official Title:** Effectiveness of Neck Stabilization Training Program in Management of Text Neck Syndrome Among Smart Gadget Users #### Organization Study ID Info **ID:** Zainab Noor Qazi #### Organization **Class:** OTHER **Full Name:** Riphah International University ### Status Module #### Completion Date **Date:** 2022-07-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-29 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-07-15 **Type:** ACTUAL #### Start Date **Date:** 2021-09-30 **Type:** ACTUAL **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2022-07-29 **Type:** ACTUAL **Study First Submit Date:** 2022-07-27 **Study First Submit QC Date:** 2022-07-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Riphah International University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** 1. To compare the effectiveness of neck stabilization training program with conventional physical therapy in management of neck pain and disability in individuals with text neck syndrome. 2. To compare the effectiveness of neck stabilization training program with conventional physical therapy in improving muscle strength and range of motion of cervical spine in individuals with text neck syndrome. **Detailed Description:** The text neck syndrome was described as a compilation of signs and symptoms due to the repetitive load, stress and pain in the body regions including; neck, shoulder joints, shoulder muscles, and thoracic region initiated by the excessive usage of smartphones for the prolonged time. The text neck syndrome is also called as 'Turtle neck neck syndrome' or 'anterior head syndrome. Neck flexion in forward direction for using any smart phone could directly affects the cervical and upper thoracic spine. It is stated that increased tilt of the head forward to fifteen degrees exaggerate about 13 Kgs of mechanical force on the cervical spine. Likewise it progresses to 18 Kgs at 30 degrees, 23 Kgs at 45 degrees and 28 Kgs at 60 degrees of forward neck flexion. The pathological consequences caused by incase of not managing the text neck could be alike to occupational overuse disease or repetitive stress and strain pathology. ### Conditions Module **Conditions:** - Neck Syndrome ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 26 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patient education Tens Hot pack Cervical muscle stretching trigger/ tender point release postural re-education cranio-cervical isometrics training of intrascapular, shoulder and upper extremity musculature resistance training with theraband **Intervention Names:** - Other: Neck Stabilization Training Program **Label:** Neck Stabilization Training Program **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patient education Tens Hot pack Cervical muscle stretching trigger/ tender point release **Intervention Names:** - Other: Conventional physical therapy **Label:** Conventional physical therapy **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Neck Stabilization Training Program **Description:** 3 times a week stretching exercises approximately 10 mins dumb bell exercises - 2 sets of 15 reps with weights varying from 1 to 2 kg cranio-cervical isometrics for 10 sec with 15 sec breaks between holds with 10-15 reps Tens 5-10 mins Hotpack 5-10 mins neck stretches home plan - 5 reps/set, 3 sets/ day **Name:** Neck Stabilization Training Program **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Conventional physical therapy **Description:** Tens 5-10 mins Hotpack 5-10 mins neck stretches home plan - 5 reps/set, 3 sets/ day **Name:** Conventional physical therapy **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** It is a functional status questionnaire with 10 items including pain, personal care, lifting, reading, headaches, concentration, work, driving, sleeping and recreation. The test can be interpreted as a raw score, with a maximum score of 50, or as percentage. Highest the score or percentage, higher will be disability. **Measure:** Neck disability index **Time Frame:** 6th week **Description:** It is a segmented numeric scale in which respondent selects a whole number (0-10). The best reflects the intensity of pain. **Measure:** NPRS **Time Frame:** 6th week **Description:** ROM of cervical flexion, extension, lateral rotation and side bending will be measured by universal goniometer. **Measure:** Range of motion **Time Frame:** 6th Week **Description:** This angle is identified as intersection of a horizontal line passing through the C7 spinous process and a line joining the midpoint of the tragus of the ear to the skin overlying the C7 spinous process. **Measure:** Cranio-vertebral angle **Time Frame:** 6th Week ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Gender (both men and women) * Age: 18-30 years * Participants using smart phones, laptops and tablets with screen time \>3 hours daily, for \>6 months. * Patient diagnosed with text neck syndrome * Trigger points in cervical muscles (trapezius, levator scapulae and scalene muscles) Exclusion Criteria: * Patient diagnosed with neck pain other than text neck syndrome **Maximum Age:** 30 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Rawalpindi **Country:** Pakistan **Facility:** Railway General Hospital **State:** Punjab #### Overall Officials **Official 1:** **Affiliation:** Riphah International University **Name:** maria Khalid, MSOMPT **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - 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: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome ### Condition Browse Module - Meshes - ID: D000013577 - Term: Syndrome ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02040779 **Brief Title:** A 12-week Safety and Efficacy Study of Beclomethasone Dipropionate (80 and 160 mcg/Day) Delivered Via Breath-Actuated Inhaler (BAI) in Patients >=12 Years Old With Persistent Asthma **Official Title:** A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 12-Week Clinical Study to Assess the Efficacy and Safety of Beclomethasone Dipropionate (80 and 160 mcg/Day) Delivered Via Breath-Actuated Inhaler (BAI) in Adolescent and Adult Patients 12 Years of Age and Older With Persistent Asthma #### Organization Study ID Info **ID:** BDB-AS-304 #### Organization **Class:** INDUSTRY **Full Name:** Teva Branded Pharmaceutical Products R&D, Inc. ### Status Module #### Completion Date **Date:** 2014-12-24 **Type:** ACTUAL #### Disp First Post Date **Date:** 2015-06-19 **Type:** ESTIMATED **Disp First Submit Date:** 2015-05-21 **Disp First Submit QC Date:** 2015-05-21 #### Expanded Access Info #### Last Update Post Date **Date:** 2021-11-09 **Type:** ACTUAL **Last Update Submit Date:** 2021-11-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-12-24 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-12-11 **Type:** ACTUAL **Results First Submit Date:** 2017-10-10 **Results First Submit QC Date:** 2017-11-07 #### Start Date **Date:** 2013-12-26 **Status Verified Date:** 2021-11 #### Study First Post Date **Date:** 2014-01-20 **Type:** ESTIMATED **Study First Submit Date:** 2014-01-16 **Study First Submit QC Date:** 2014-01-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Teva Branded Pharmaceutical Products R&D, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a randomized, double-blind, placebo-controlled parallel-group study. Participants will be randomly assigned to receive treatment with beclomethasone dipropionate at a dosage of 80 or 160 mcg/day delivered via a Breath-Actuated Inhaler (BAI); or a matching BAI placebo, in a 1:1:1 ratio after a 14- to 21-day run-in period. Participants and investigators will remain blinded to randomized treatment assignment during the study ### Conditions Module **Conditions:** - Persistent Asthma **Keywords:** - asthma - breath-actuated inhaler - beclomethasone ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 273 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **Intervention Names:** - Drug: Beclomethasone dipropionate breath-actuated inhaler - Drug: albuterol/salbutamol **Label:** BDP 80 mcg BAI **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **Intervention Names:** - Drug: Beclomethasone dipropionate breath-actuated inhaler - Drug: albuterol/salbutamol **Label:** BDP 160 mcg BAI **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **Intervention Names:** - Drug: Placebo breath-actuated inhaler - Drug: albuterol/salbutamol **Label:** Placebo BAI **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - BDP 160 mcg BAI - BDP 80 mcg BAI **Description:** Beclomethasone dipropionate (BDP) breath-actuated inhaler (BAI) given in dosages of either 40 mcg/inhalation or 80 mcg/inhalation. Study drug was administered twice each day, in the morning and in the evening, after the completion of the asthma symptom score and the PEF measurements, in that order. **Name:** Beclomethasone dipropionate breath-actuated inhaler **Other Names:** - BDP **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo BAI **Description:** Placebo was provided in matching breath-actuated inhaler (BAI) devices. The placebo devices were identical to the devices used to deliver active drug. Placebo was administered twice each day, in the morning and in the evening, after the completion of the asthma symptom score and the PEF measurements, in that order. **Name:** Placebo breath-actuated inhaler **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - BDP 160 mcg BAI - BDP 80 mcg BAI - Placebo BAI **Description:** Rescue medication (albuterol/salbutamol hydrofluoroalkane (HFA) MDI \[90 mcg ex-actuator\] or equivalent) for use on an as-needed basis for the immediate relief of asthma symptoms throughout the treatment period **Name:** albuterol/salbutamol **Other Names:** - bronchodilators **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The primary efficacy variable was the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) FEV1 AUEC(0-12wk). Pulmonary function measurements such as FEV1 were obtained electronically by spirometry at the randomization visit (Day 1), each treatment visit (Weeks 2, 4, 8 and 12) and any unscheduled visit (such as the early termination visit). This summary is based on observed values recorded as 'best attempt'. The least-square (LS) means, difference of LS means and its 95% confidence interval (CI), and p-value represent the results obtained from the analysis of covariance with covariate adjustment for baseline, sex, age, current asthma therapy, and treatment. **Measure:** Standardized Baseline-Adjusted Trough Morning Forced Expiratory Volume in One Minute (FEV1) Area Under the Effect Curve From Time Zero to 12 Weeks (AUEC(0-12wk)) by Actual Treatment Received **Time Frame:** Baseline (Day 1 predose), weeks 2, 4, 8 and 12 #### Secondary Outcomes **Description:** Change from baseline in the weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF by handheld spirometer over the 12-week treatment period. PEF were determined twice daily, in the morning and in the evening, before administration of study drug or rescue medications. A handheld spirometer was provided to patients and used to determine the morning and evening PEF throughout the study. The spirometer was programmed to record the highest PEF obtained from 3 valid attempts. Baseline was defined as the average of recorded trough morning PEF assessments over the 7 days prior to the first dose of double-blind study treatment, including the morning assessment at the randomization visit. The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction. **Measure:** Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Rate Over the 12-Week Treatment Period **Time Frame:** Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 **Description:** A hand-held peak flow meter was provided to patients at the screening visit and used to determine the morning and evening PEF throughout the course of the study. The patient recorded the highest value of 3 measurements obtained in the morning and evening in the patient diary. Baseline in evening PEF is defined as the average of recorded evening PEF assessments over the 7-day window before randomization. The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction. **Measure:** Change From Baseline in Weekly Average of Daily Evening Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period **Time Frame:** Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 **Description:** Change from baseline in the use of rescue medication, albuterol/salbutamol, during the treatment period offers an indication of asthma control. The LS means, difference of LS means and its 95% CI, and p-value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week and treatment by week interaction. Baseline was defined as the average of recorded daily usage of albuterol/salbutamol inhalation aerosol over the 7 days prior to the first dose of double-blind study treatment, including morning usage at the randomization visit. **Measure:** Change From Baseline in Weekly Average of Total Daily Use of Albuterol/Salbutamol Inhalation Aerosol Over Weeks 1-12 **Time Frame:** Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 **Description:** Asthma symptom scores were recorded in the patient's diary each morning and evening before determining FEV1 and PEF and before administration of study or rescue medications. The Daytime Symptom Score was recorded in the evening on a scale of 0 (No symptoms during the day) to 5 (Symptoms so severe that I could not go to work or perform normal daily activities) plus the Nighttime Symptom Score in the morning on a scale of 0 (No symptoms during the night) to 4 (Symptoms so severe that I did not sleep at all) for a total score range of 0-9. Baseline was defined as the average of recorded daily asthma symptom scores (average of daytime and nighttime score) over the 7 days prior to the first dose of study treatment, including the morning assessment at the randomization visit. The LS means, difference of LS means and its 95% CI, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, **Measure:** Change From Baseline in Weekly Average of Total Daily Asthma Symptom Score Over the 12-Week Treatment Period **Time Frame:** Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 **Description:** The time to patient study drug treatment withdrawal due to worsening asthma was defined as the number of days elapsed from the date of randomization to the date of withdrawal due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety. An example of alert criteria is: * FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1). * Other criteria as defined in the protocol. **Measure:** Kaplan-Meier Estimates of Time to Study Drug Treatment Withdrawal Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period **Time Frame:** Treatment period: daily from Day 1 up to Week 12 **Description:** A count of participants who were withdrawn from the study due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety. An example of alert criteria is: * FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1). * Other criteria as defined in the protocol. **Measure:** Number of Participants Withdrawn From Study Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period **Time Frame:** Treatment period: Day 1 up to Week 12 **Description:** An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent 1 of the outcomes listed in this definition. **Measure:** Participants With Treatment-Emergent Adverse Events (TEAEs) **Time Frame:** Day 1 up to Week 12 **Description:** Criteria for the select vital signs that showed a potentially clinically relevant abnormal result are: * Sitting systolic BP (low); \<=90 mm Hg and decrease of \>=20 mm Hg from baseline * Sitting diastolic BP (high): \>=105 mm Hg and increase of \>=15 mm Hg from baseline Baseline is defined as the last available assessment prior to the first dose of double-blind study treatment (usually Day 1 predose). **Measure:** Participants With Potentially Clinically Relevant Abnormal Vital Sign Results During the Treatment Period **Time Frame:** Baseline (Day 1 predose), Visits at weeks 2, 4, 8, 12 **Description:** Oropharyngeal examinations were performed at every visit by a qualified healthcare professional: during treatment visits are summarized. Any visual evidence of oral candidiasis during the treatment period of the study was evaluated by obtaining and analyzing a swab of the suspect area for culturing. Appropriate therapy was to be initiated immediately at the discretion of the investigator and was not to be delayed for culture confirmation. **Measure:** Participants With Findings During Oropharyngeal Examination During Treatment **Time Frame:** Visits at weeks 2, 4, 8, 12 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Severity of Disease: The patient has persistent asthma, with an forced expiratory volume in 1 second (FEV1) 40%-85% of the value predicted for age, height, sex, and race as per the National Health and Nutrition Examination Survey (NHANES III) reference values at screening visit (SV) (Hankinson et al 1999). * Current asthma therapy: The patient is currently being treated with 1 of the following: 1) inhaled corticosteroids (ICSs) at a stable daily dose of less than or equal to 220 mcg/day fluticasone propionate via metered dose inhaler (MDI) or equivalent for a minimum of 4 weeks (28 days) before screening visit, or 2) a stable daily dosage of non-corticosteroid therapy, including leukotriene modifiers, theophylline, chromones, or short-acting beta-2 agonists (SABAs) alone or in combination for a minimum of 4 weeks (28 days) before screening visit (SV). * Reversibility of disease: The patient has demonstrated at least 15% and at least 200 mL increase from baseline FEV1 (patients age 18 and older) within 30 minutes after 2-4 inhalations of albuterol/salbutamol hydrofluoroalkane (HFA) MDI (90 mcg ex-actuator) or equivalent at SV or on retesting. - Other criteria apply, please contact the investigator for more information Exclusion Criteria: * The patient has a history of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures. * The patient is a pregnant or lactating female or plans to become pregnant. * The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation. * The patient currently smokes or has a smoking history of 10 pack-years or more (a pack-year is defined as smoking 1 pack of cigarettes/day for 1 year). The patient may not have used tobacco products within the past year. * The patient has had an asthma exacerbation requiring oral corticosteroids within 1 month before SV, or has had any hospitalization for asthma within 2 months before SV. * The patient has historical or current evidence of a clinically significant disease. Significant disease is defined as any disease that in the medical judgment of the investigator would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study. * Other criteria apply, please contact the investigator for more information **Minimum Age:** 12 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Huntington Beach **Country:** United States **Facility:** Teva Investigational Site 12813 **State:** California **Location 2:** **City:** Mission Viejo **Country:** United States **Facility:** Teva Investigational Site 10944 **State:** California **Location 3:** **City:** Orange **Country:** United States **Facility:** Teva Investigational Site 10946 **State:** California **Location 4:** **City:** Rolling Hills Estates **Country:** United States **Facility:** Teva Investigational Site 10963 **State:** California **Location 5:** **City:** San Diego **Country:** United States **Facility:** Teva Investigational Site 10960 **State:** California **Location 6:** **City:** San Diego **Country:** United States **Facility:** Teva Investigational Site 10973 **State:** California **Location 7:** **City:** San Jose **Country:** United States **Facility:** Teva Investigational Site 10975 **State:** California **Location 8:** **City:** Centennial **Country:** United States **Facility:** Teva Investigational Site 10948 **State:** Colorado **Location 9:** **City:** Centennial **Country:** United States **Facility:** Teva Investigational Site 10958 **State:** Colorado **Location 10:** **City:** Colorado Springs **Country:** United States **Facility:** Teva Investigational Site 10957 **State:** Colorado **Location 11:** **City:** Sarasota **Country:** United States **Facility:** Teva Investigational Site 12814 **State:** Florida **Location 12:** **City:** Tallahassee **Country:** United States **Facility:** Teva Investigational Site 10962 **State:** Florida **Location 13:** **City:** Savannah **Country:** United States **Facility:** Teva Investigational Site 12809 **State:** Georgia **Location 14:** **City:** Indianapolis **Country:** United States **Facility:** Teva Investigational Site 10947 **State:** Indiana **Location 15:** **City:** Iowa City **Country:** United States **Facility:** Teva Investigational Site 10943 **State:** Iowa **Location 16:** **City:** Baltimore **Country:** United States **Facility:** Teva Investigational Site 10954 **State:** Maryland **Location 17:** **City:** Bethesda **Country:** United States **Facility:** Teva Investigational Site 12940 **State:** Maryland **Location 18:** **City:** North Dartmouth **Country:** United States **Facility:** Teva Investigational Site 10955 **State:** Massachusetts **Location 19:** **City:** Minneapolis **Country:** United States **Facility:** Teva Investigational Site 10941 **State:** Minnesota **Location 20:** **City:** Columbia **Country:** United States **Facility:** Teva Investigational Site 10970 **State:** Missouri **Location 21:** **City:** Rolla **Country:** United States **Facility:** Teva Investigational Site 10968 **State:** Missouri **Location 22:** **City:** Bozeman **Country:** United States **Facility:** Teva Investigational Site 10972 **State:** Montana **Location 23:** **City:** Missoula **Country:** United States **Facility:** Teva Investigational Site 12941 **State:** Montana **Location 24:** **City:** Bellevue **Country:** United States **Facility:** Teva Investigational Site 10942 **State:** Nebraska **Location 25:** **City:** Skillman **Country:** United States **Facility:** Teva Investigational Site 10959 **State:** New Jersey **Location 26:** **City:** Raleigh **Country:** United States **Facility:** Teva Investigational Site 10945 **State:** North Carolina **Location 27:** **City:** Cincinnati **Country:** United States **Facility:** Teva Investigational Site 12810 **State:** Ohio **Location 28:** **City:** Sylvania **Country:** United States **Facility:** Teva Investigational Site 10974 **State:** Ohio **Location 29:** **City:** Oklahoma City **Country:** United States **Facility:** Teva Investigational Site 12805 **State:** Oklahoma **Location 30:** **City:** Oklahoma City **Country:** United States **Facility:** Teva Investigational Site 12942 **State:** Oklahoma **Location 31:** **City:** Tulsa **Country:** United States **Facility:** Teva Investigational Site 10951 **State:** Oklahoma **Location 32:** **City:** Lake Oswego **Country:** United States **Facility:** Teva Investigational Site 10940 **State:** Oregon **Location 33:** **City:** Medford **Country:** United States **Facility:** Teva Investigational Site 10952 **State:** Oregon **Location 34:** **City:** Portland **Country:** United States **Facility:** Teva Investigational Site 10956 **State:** Oregon **Location 35:** **City:** Pittsburgh **Country:** United States **Facility:** Teva Investigational Site 12939 **State:** Pennsylvania **Location 36:** **City:** Orangeburg **Country:** United States **Facility:** Teva Investigational Site 12806 **State:** South Carolina **Location 37:** **City:** Knoxville **Country:** United States **Facility:** Teva Investigational Site 12811 **State:** Tennessee **Location 38:** **City:** Austin **Country:** United States **Facility:** Teva Investigational Site 10969 **State:** Texas **Location 39:** **City:** Boerne **Country:** United States **Facility:** Teva Investigational Site 12812 **State:** Texas **Location 40:** **City:** Dallas **Country:** United States **Facility:** Teva Investigational Site 10949 **State:** Texas **Location 41:** **City:** El Paso **Country:** United States **Facility:** Teva Investigational Site 10953 **State:** Texas **Location 42:** **City:** Houston **Country:** United States **Facility:** Teva Investigational Site 12807 **State:** Texas **Location 43:** **City:** New Braunfels **Country:** United States **Facility:** Teva Investigational Site 10950 **State:** Texas **Location 44:** **City:** San Antonio **Country:** United States **Facility:** Teva Investigational Site 10961 **State:** Texas **Location 45:** **City:** Waco **Country:** United States **Facility:** Teva Investigational Site 12808 **State:** Texas **Location 46:** **City:** Seattle **Country:** United States **Facility:** Teva Investigational Site 10967 **State:** Washington **Location 47:** **City:** Greenfield **Country:** United States **Facility:** Teva Investigational Site 10964 **State:** Wisconsin #### Overall Officials **Official 1:** **Affiliation:** Teva Branded Pharmaceutical Products R&D, Inc. **Name:** Medical Director, MD **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Hampel FC Jr, Carr W, Gillespie M, Small CJ. Evaluation of beclomethasone dipropionate (80 and 160 micrograms/day) delivered via a breath-actuated inhaler for persistent asthma. Allergy Asthma Proc. 2017 Nov 8;38(6):419-430. doi: 10.2500/aap.2017.38.4089. Epub 2017 Sep 8. **PMID:** 28886758 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001982 - Term: Bronchial Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000008173 - Term: Lung Diseases, Obstructive - ID: D000008171 - Term: Lung Diseases - ID: D000012130 - Term: Respiratory Hypersensitivity - ID: D000006969 - Term: Hypersensitivity, Immediate - ID: D000006967 - Term: Hypersensitivity - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4556 - Name: Asthma - Relevance: HIGH - As Found: Asthma - 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: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M14967 - Name: Respiratory Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M10020 - Name: Hypersensitivity, Immediate - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001249 - Term: Asthma ### Intervention Browse Module - Ancestors - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018927 - Term: Anti-Asthmatic Agents - ID: D000019141 - Term: Respiratory System Agents - ID: D000015149 - Term: Tocolytic Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000058666 - Term: Adrenergic beta-2 Receptor Agonists - ID: D000000318 - Term: Adrenergic beta-Agonists - ID: D000000322 - Term: Adrenergic Agonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists ### Intervention Browse Module - Browse Branches - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infl - Name: Anti-Inflammatory Agents ### Intervention Browse Module - Browse Leaves - ID: M3767 - Name: Albuterol - Relevance: HIGH - As Found: Diameter - ID: M4800 - Name: Beclomethasone - Relevance: HIGH - As Found: Timed - ID: M5269 - Name: Bronchodilator Agents - Relevance: HIGH - As Found: Pain level - ID: M20963 - Name: Anti-Asthmatic Agents - Relevance: LOW - As Found: Unknown - ID: M21137 - Name: Respiratory System Agents - Relevance: LOW - As Found: Unknown - ID: M17869 - Name: Tocolytic Agents - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M3670 - Name: Adrenergic beta-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 - 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 ### Intervention Browse Module - Meshes - ID: D000001507 - Term: Beclomethasone - ID: D000000420 - Term: Albuterol - ID: D000001993 - Term: Bronchodilator Agents ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Placebo BAI **Deaths Num At Risk:** 91 **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** EG000 **Other Num at Risk:** 91 **Serious Number Affected:** 1 **Serious Number At Risk:** 91 **Title:** Placebo BAI **Group ID:** EG001 **Title:** BDP 80 mcg BAI **Deaths Num At Risk:** 90 **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** EG001 **Other Num at Risk:** 90 **Serious Number At Risk:** 90 **Title:** BDP 80 mcg BAI **Group ID:** EG002 **Title:** BDP 160 mcg BAI **Deaths Num At Risk:** 92 **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** EG002 **Other Num at Risk:** 92 **Serious Number At Risk:** 92 **Title:** BDP 160 mcg BAI **Frequency Threshold:** 5 #### Serious Events **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (16.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 91 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 90 **Group ID:** EG002 **Num At Risk:** 92 **Term:** Asthma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (16.1) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 91 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 90 **Group ID:** EG002 **Num At Risk:** 92 **Time Frame:** Day 1 to Week 12 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 91 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 273 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo BAI **Description:** Placebo breath-actuated inhaler (BAI) twice daily. ### Group **ID:** BG001 **Title:** BDP 80 mcg BAI **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. ### Group **ID:** BG002 **Title:** BDP 160 mcg BAI **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. ### Group **ID:** BG003 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 14.82 **Value:** 37.2 #### Measurement **Group ID:** BG001 **Spread:** 15.02 **Value:** 38.8 #### Measurement **Group ID:** BG002 **Spread:** 16.05 **Value:** 37.4 #### Measurement **Group ID:** BG003 **Spread:** 15.27 **Value:** 37.8 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 91 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 273 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 46 #### Measurement **Group ID:** BG001 **Value:** 54 #### Measurement **Group ID:** BG002 **Value:** 56 #### Measurement **Group ID:** BG003 **Value:** 156 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 45 #### Measurement **Group ID:** BG001 **Value:** 36 #### Measurement **Group ID:** BG002 **Value:** 36 #### Measurement **Group ID:** BG003 **Value:** 117 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 91 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 273 **Class Title:** ### 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 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 6 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 13 #### Measurement **Group ID:** BG001 **Value:** 17 #### Measurement **Group ID:** BG002 **Value:** 14 #### Measurement **Group ID:** BG003 **Value:** 44 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 73 #### Measurement **Group ID:** BG001 **Value:** 64 #### Measurement **Group ID:** BG002 **Value:** 72 #### Measurement **Group ID:** BG003 **Value:** 209 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 5 #### Measurement **Group ID:** BG003 **Value:** 13 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 91 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 273 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 23.848 **Value:** 82.27 #### Measurement **Group ID:** BG001 **Spread:** 22.382 **Value:** 85.30 #### Measurement **Group ID:** BG002 **Spread:** 20.577 **Value:** 80.29 #### Measurement **Group ID:** BG003 **Spread:** 22.316 **Value:** 82.60 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 91 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 273 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.473 **Value:** 169.28 #### Measurement **Group ID:** BG001 **Spread:** 10.447 **Value:** 170.88 #### Measurement **Group ID:** BG002 **Spread:** 8.657 **Value:** 168.78 #### Measurement **Group ID:** BG003 **Spread:** 9.554 **Value:** 169.64 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 90 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 272 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 6.9051 **Value:** 28.383 #### Measurement **Group ID:** BG001 **Spread:** 7.9371 **Value:** 29.266 #### Measurement **Group ID:** BG002 **Spread:** 6.7751 **Value:** 28.136 #### Measurement **Group ID:** BG003 **Spread:** 7.2109 **Value:** 28.591 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 90 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 272 **Class Title:** ### 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 **Category Title:** <3 months #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 **Category Title:** 3 months to <6 months #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 2 **Category Title:** 6 months to <1 year #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 10 **Category Title:** 1 year to < 5 years #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 10 #### Measurement **Group ID:** BG003 **Value:** 27 **Category Title:** 5 years to <10 years #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 16 #### Measurement **Group ID:** BG002 **Value:** 18 #### Measurement **Group ID:** BG003 **Value:** 46 **Category Title:** 10 years to <15 years #### Measurement **Group ID:** BG000 **Value:** 65 #### Measurement **Group ID:** BG001 **Value:** 60 #### Measurement **Group ID:** BG002 **Value:** 62 #### Measurement **Group ID:** BG003 **Value:** 187 **Category Title:** >=15 years #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 91 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 273 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 35 #### Measurement **Group ID:** BG001 **Value:** 34 #### Measurement **Group ID:** BG002 **Value:** 35 #### Measurement **Group ID:** BG003 **Value:** 104 **Category Title:** Inhaled corticosteroid #### Measurement **Group ID:** BG000 **Value:** 56 #### Measurement **Group ID:** BG001 **Value:** 56 #### Measurement **Group ID:** BG002 **Value:** 57 #### Measurement **Group ID:** BG003 **Value:** 169 **Category Title:** Non-corticosteroid #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 91 **Group ID:** BG001 **Value:** 90 **Group ID:** BG002 **Value:** 92 **Group ID:** BG003 **Value:** 273 **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:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Weight **Unit of Measure:** kg ### Measure 5 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** One participant did not have a height recorded **Title:** Height **Unit of Measure:** cm ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** One participant did not have a height recorded, therefore BMI could not be calculated. **Title:** Body Mass Index **Unit of Measure:** kg/m^2 ### Measure 7 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Duration of Asthma **Unit of Measure:** Participants ### Measure 8 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Current Asthma Therapy **Unit of Measure:** Participants **Population Description:** Intent-to-treat (ITT) Population ## Results Section - More Information Module ### Certain Agreement **Other Details:** Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Teva Branded Pharmaceutical Products R&D **Phone:** 215-591-3000 **Title:** Director, Clinical Research ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.048 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.185 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 160 mcg BAI - Placebo BAI **Group Description:** A fixed-sequence multiple testing procedure was used while controlling the family-wise error rate at 5%. If the 2-sided p-value resulting from the ANCOVA model for comparing beclomethasone dipropionate BAI 160 mcg/day versus placebo was less than 0.05, then the comparison of the 80 mcg/day versus placebo was to be interpreted inferentially. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0010 **P-Value Comment:** ANCOVA model with effects due to baseline trough morning FEV1, sex, age, current protocol-allowed asthma therapy (ICS or non-corticosteroid therapy) at the time of screening visit and during the run-in period and treatment. **Parameter Type:** LSM difference **Parameter Value:** 0.116 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.054 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.193 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 80 mcg BAI - Placebo BAI **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0005 **P-Value Comment:** ANCOVA model with effects due to baseline trough morning FEV1, sex, age, current protocol-allowed asthma therapy (ICS or non-corticosteroid therapy) at the time of screening visit and during the run-in period and treatment. **Parameter Type:** LSM difference **Parameter Value:** 0.124 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 0.202 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 15.621 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 160 mcg BAI - Placebo BAI **Group Description:** Treatment comparisons began with am PEF for BDP 160 mcg BAI vs placebo. If the p-value was ≤0.05, the next comparisons of interest were made 1) the next secondary outcome comparison for BDP 160 mcg BAI vs placebo and 2) the am PEF for BDP 80 mcg BAI vs placebo. This procedure allowed for control of the Type I error for comparisons at a particular BAI treatment over the 5 secondary endpoints, as well as comparisons within an endpoint. It did not control the overall Type I error. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0443 **P-Value Comment:** a priori threshold for significance of 0.05. **Parameter Type:** LSM difference **Parameter Value:** 7.911 **Statistical Comment:** **Statistical Method:** mixed model for repeated measures **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 5.843 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 21.446 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 160 mcg BAI - Placebo BAI **Group Description:** Treatment comparisons began with am PEF for BDP 160 mcg BAI vs placebo. If the p-value was ≤0.05, the next comparisons of interest were made 1) the next secondary outcome comparison for BDP 160 mcg BAI vs placebo and 2) the am PEF for BDP 80 mcg BAI vs placebo. This procedure allowed for control of the Type I error for comparisons at a particular BAI treatment over the 5 secondary endpoints, as well as comparisons within an endpoint. It did not control the overall Type I error. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0007 **P-Value Comment:** a priori threshold for significance of 0.05. **Parameter Type:** LSM difference **Parameter Value:** 13.645 **Statistical Comment:** **Statistical Method:** mixed model for repeated measures **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -2.905 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 13.715 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 160 mcg BAI - Placebo BAI **Group Description:** Treatment comparisons began with am PEF for BDP 160 mcg BAI vs placebo. If the p-value was ≤0.05, the next comparisons of interest were made 1) the next secondary outcome comparison for BDP 160 mcg BAI vs placebo and 2) the am PEF for BDP 80 mcg BAI vs placebo. This procedure allowed for control of the Type I error for comparisons at a particular BAI treatment over the 5 secondary endpoints, as well as comparisons within an endpoint. It did not control the overall Type I error. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.2014 **P-Value Comment:** a priori threshold for significance of 0.05. **Parameter Type:** LSM difference **Parameter Value:** 5.405 **Statistical Comment:** **Statistical Method:** mixed model for repeated measures **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 2.500 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 19.303 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 160 mcg BAI - Placebo BAI **Group Description:** Treatment comparisons began with am PEF for BDP 160 mcg BAI vs placebo. If the p-value was ≤0.05, the next comparisons of interest were made 1) the next secondary outcome comparison for BDP 160 mcg BAI vs placebo and 2) the am PEF for BDP 80 mcg BAI vs placebo. This procedure allowed for control of the Type I error for comparisons at a particular BAI treatment over the 5 secondary endpoints, as well as comparisons within an endpoint. It did not control the overall Type I error. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0112 **P-Value Comment:** a priori threshold for significance of 0.05. **Parameter Type:** LSM difference **Parameter Value:** 10.902 **Statistical Comment:** **Statistical Method:** mixed model for repeated measures **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -0.708 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.068 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 160 mcg BAI - Placebo BAI **Group Description:** Treatment comparisons began with am PEF for BDP 160 mcg BAI vs placebo. If the p-value was ≤0.05, the next comparisons of interest were made 1) the next secondary outcome comparison for BDP 160 mcg BAI vs placebo and 2) the am PEF for BDP 80 mcg BAI vs placebo. This procedure allowed for control of the Type I error for comparisons at a particular BAI treatment over the 5 secondary endpoints, as well as comparisons within an endpoint. It did not control the overall Type I error. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0175 **P-Value Comment:** a priori threshold for significance of 0.05. **Parameter Type:** LSM difference **Parameter Value:** -0.388 **Statistical Comment:** **Statistical Method:** mixed model for repeated measures **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.678 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.038 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 80 mcg BAI - Placebo BAI **Group Description:** Treatment comparisons began with am PEF for BDP 160 mcg BAI vs placebo. If the p-value was ≤0.05, the next comparisons of interest were made 1) the next secondary outcome comparison for BDP 160 mcg BAI vs placebo and 2) the am PEF for BDP 80 mcg BAI vs placebo. This procedure allowed for control of the Type I error for comparisons at a particular BAI treatment over the 5 secondary endpoints, as well as comparisons within an endpoint. It did not control the overall Type I error. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0285 **P-Value Comment:** a priori threshold for significance of 0.05. **Parameter Type:** LSM difference **Parameter Value:** -0.358 **Statistical Comment:** **Statistical Method:** mixed model for repeated measures **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -0.263 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.011 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 160 mcg BAI - Placebo BAI **Group Description:** Treatment comparisons began with am PEF for BDP 160 mcg BAI vs placebo. If the p-value was ≤0.05, the next comparisons of interest were made 1) the next secondary outcome comparison for BDP 160 mcg BAI vs placebo and 2) the am PEF for BDP 80 mcg BAI vs placebo. This procedure allowed for control of the Type I error for comparisons at a particular BAI treatment over the 5 secondary endpoints, as well as comparisons within an endpoint. It did not control the overall Type I error. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0335 **P-Value Comment:** a priori threshold for significance of 0.05. **Parameter Type:** LSM difference **Parameter Value:** -0.137 **Statistical Comment:** **Statistical Method:** mixed model for repeated measures **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.255 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.001 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** BDP 80 mcg BAI - Placebo BAI **Group Description:** Treatment comparisons began with am PEF for BDP 160 mcg BAI vs placebo. If the p-value was ≤0.05, the next comparisons of interest were made 1) the next secondary outcome comparison for BDP 160 mcg BAI vs placebo and 2) the am PEF for BDP 80 mcg BAI vs placebo. This procedure allowed for control of the Type I error for comparisons at a particular BAI treatment over the 5 secondary endpoints, as well as comparisons within an endpoint. It did not control the overall Type I error. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0509 **P-Value Comment:** a priori threshold for significance of 0.05. **Parameter Type:** LSM difference **Parameter Value:** -0.127 **Statistical Comment:** **Statistical Method:** mixed model for repeated measures **Tested Non-Inferiority:** ### Outcome Measure 6 ### Outcome Measure 7 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.2384 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0208 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0252 - **Upper Limit:** - **Value:** 0.048 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0254 - **Upper Limit:** - **Value:** 0.171 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.0248 - **Upper Limit:** - **Value:** 0.164 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.8224 - **Upper Limit:** - **Value:** -0.795 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.8241 - **Upper Limit:** - **Value:** 12.849 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.7735 - **Upper Limit:** - **Value:** 7.116 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.0380 - **Upper Limit:** - **Value:** -0.797 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 35.0507 - **Upper Limit:** - **Value:** 10.105 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.9908 - **Upper Limit:** - **Value:** 4.608 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1162 - **Upper Limit:** - **Value:** -0.010 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.1155 - **Upper Limit:** - **Value:** -0.368 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.1153 - **Upper Limit:** - **Value:** -0.398 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0460 - **Upper Limit:** - **Value:** -0.166 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0463 - **Upper Limit:** - **Value:** -0.293 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.0454 - **Upper Limit:** - **Value:** -0.304 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** Insufficient number of participants withdrawn - **Group ID:** OG000 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Insufficient number of participants withdrawn - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Insufficient number of participants withdrawn - **Group ID:** OG002 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 **Title:** **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 - **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:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **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:** 1 - **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 9 **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **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:** **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:** 1 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The primary efficacy variable was the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) FEV1 AUEC(0-12wk). Pulmonary function measurements such as FEV1 were obtained electronically by spirometry at the randomization visit (Day 1), each treatment visit (Weeks 2, 4, 8 and 12) and any unscheduled visit (such as the early termination visit). This summary is based on observed values recorded as 'best attempt'. The least-square (LS) means, difference of LS means and its 95% confidence interval (CI), and p-value represent the results obtained from the analysis of covariance with covariate adjustment for baseline, sex, age, current asthma therapy, and treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** The full analysis set (FAS) included all patients in the intent to treat (ITT) population who received at least 1 dose of study drug and had at least 1 postbaseline trough morning (pre-dose and pre-rescue bronchodilator) assessment of FEV1. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 1 predose), weeks 2, 4, 8 and 12 **Title:** Standardized Baseline-Adjusted Trough Morning Forced Expiratory Volume in One Minute (FEV1) Area Under the Effect Curve From Time Zero to 12 Weeks (AUEC(0-12wk)) by Actual Treatment Received **Type:** PRIMARY **Unit of Measure:** liters ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 2 **Description:** Change from baseline in the weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF by handheld spirometer over the 12-week treatment period. PEF were determined twice daily, in the morning and in the evening, before administration of study drug or rescue medications. A handheld spirometer was provided to patients and used to determine the morning and evening PEF throughout the study. The spirometer was programmed to record the highest PEF obtained from 3 valid attempts. Baseline was defined as the average of recorded trough morning PEF assessments over the 7 days prior to the first dose of double-blind study treatment, including the morning assessment at the randomization visit. The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Full analysis set (FAS) **Reporting Status:** POSTED **Time Frame:** Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 **Title:** Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Rate Over the 12-Week Treatment Period **Type:** SECONDARY **Unit of Measure:** L/minute ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 3 **Description:** A hand-held peak flow meter was provided to patients at the screening visit and used to determine the morning and evening PEF throughout the course of the study. The patient recorded the highest value of 3 measurements obtained in the morning and evening in the patient diary. Baseline in evening PEF is defined as the average of recorded evening PEF assessments over the 7-day window before randomization. The LS means, difference of LS means and its 95% confidence interval, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week, and treatment by week interaction. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Full analysis set **Reporting Status:** POSTED **Time Frame:** Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 **Title:** Change From Baseline in Weekly Average of Daily Evening Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period **Type:** SECONDARY **Unit of Measure:** L/minute ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 4 **Description:** Change from baseline in the use of rescue medication, albuterol/salbutamol, during the treatment period offers an indication of asthma control. The LS means, difference of LS means and its 95% CI, and p-value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, treatment, week and treatment by week interaction. Baseline was defined as the average of recorded daily usage of albuterol/salbutamol inhalation aerosol over the 7 days prior to the first dose of double-blind study treatment, including morning usage at the randomization visit. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** FAS **Reporting Status:** POSTED **Time Frame:** Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 **Title:** Change From Baseline in Weekly Average of Total Daily Use of Albuterol/Salbutamol Inhalation Aerosol Over Weeks 1-12 **Type:** SECONDARY **Unit of Measure:** inhalations ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 5 **Description:** Asthma symptom scores were recorded in the patient's diary each morning and evening before determining FEV1 and PEF and before administration of study or rescue medications. The Daytime Symptom Score was recorded in the evening on a scale of 0 (No symptoms during the day) to 5 (Symptoms so severe that I could not go to work or perform normal daily activities) plus the Nighttime Symptom Score in the morning on a scale of 0 (No symptoms during the night) to 4 (Symptoms so severe that I did not sleep at all) for a total score range of 0-9. Baseline was defined as the average of recorded daily asthma symptom scores (average of daytime and nighttime score) over the 7 days prior to the first dose of study treatment, including the morning assessment at the randomization visit. The LS means, difference of LS means and its 95% CI, and p value are obtained from the mixed model for repeated measures analysis with covariate adjustment for baseline, sex, age, current asthma therapy, **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Full analysis set **Reporting Status:** POSTED **Time Frame:** Baseline (Days -6 to Day 1 pre-dose), daily up to Week 12 **Title:** Change From Baseline in Weekly Average of Total Daily Asthma Symptom Score Over the 12-Week Treatment Period **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 6 **Description:** The time to patient study drug treatment withdrawal due to worsening asthma was defined as the number of days elapsed from the date of randomization to the date of withdrawal due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety. An example of alert criteria is: * FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1). * Other criteria as defined in the protocol. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Full analysis set **Reporting Status:** POSTED **Time Frame:** Treatment period: daily from Day 1 up to Week 12 **Title:** Kaplan-Meier Estimates of Time to Study Drug Treatment Withdrawal Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period **Type:** SECONDARY **Unit of Measure:** days ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 7 **Description:** A count of participants who were withdrawn from the study due to meeting stopping criteria. Alert criteria for individual patients with worsening asthma were designed to ensure patient safety. The investigator determined whether the patient's overall clinical picture is consistent with worsening asthma and if the patient should be withdrawn from study drug treatment (but not the study) and be placed on appropriate asthma therapy in the interest of patient safety. An example of alert criteria is: * FEV1 as measured at the study center is below the FEV1 stability limit value calculated at randomization visit (Day 1). * Other criteria as defined in the protocol. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Full analysis set **Reporting Status:** POSTED **Time Frame:** Treatment period: Day 1 up to Week 12 **Title:** Number of Participants Withdrawn From Study Due to Meeting Stopping Criteria for Worsening Asthma During the 12-Week Treatment Period **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 8 **Description:** An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent 1 of the outcomes listed in this definition. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The safety population included all randomly assigned patients (ITT population) who took 1 or more doses of study drug. In this population, treatment was assigned based upon the treatment patients actually received, regardless of the treatment to which they were randomized. **Reporting Status:** POSTED **Time Frame:** Day 1 up to Week 12 **Title:** Participants With Treatment-Emergent Adverse Events (TEAEs) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 9 **Description:** Criteria for the select vital signs that showed a potentially clinically relevant abnormal result are: * Sitting systolic BP (low); \<=90 mm Hg and decrease of \>=20 mm Hg from baseline * Sitting diastolic BP (high): \>=105 mm Hg and increase of \>=15 mm Hg from baseline Baseline is defined as the last available assessment prior to the first dose of double-blind study treatment (usually Day 1 predose). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety population **Reporting Status:** POSTED **Time Frame:** Baseline (Day 1 predose), Visits at weeks 2, 4, 8, 12 **Title:** Participants With Potentially Clinically Relevant Abnormal Vital Sign Results During the Treatment Period **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI #### Outcome Measure 10 **Description:** Oropharyngeal examinations were performed at every visit by a qualified healthcare professional: during treatment visits are summarized. Any visual evidence of oral candidiasis during the treatment period of the study was evaluated by obtaining and analyzing a swab of the suspect area for culturing. Appropriate therapy was to be initiated immediately at the discretion of the investigator and was not to be delayed for culture confirmation. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety population **Reporting Status:** POSTED **Time Frame:** Visits at weeks 2, 4, 8, 12 **Title:** Participants With Findings During Oropharyngeal Examination During Treatment **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** OG000 **Title:** Placebo BAI ##### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** OG001 **Title:** BDP 80 mcg BAI ##### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** OG002 **Title:** BDP 160 mcg BAI ### Participant Flow Module #### Group **Description:** Placebo breath-actuated inhaler (BAI) twice daily. **ID:** FG000 **Title:** Placebo BAI #### Group **Description:** 40 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 80 mcg/day. **ID:** FG001 **Title:** BDP 80 mcg BAI #### Group **Description:** 80 mcg beclomethasone dipropionate (BDP) via breath-actuated inhaler (BAI) twice daily for a total of 160 mcg/day. **ID:** FG002 **Title:** BDP 160 mcg BAI #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ##### Withdraw **Type:** Non-compliance ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 91 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 90 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 92 ##### Milestone **Type:** Full Analysis Set (FAS) ###### Achievement **Group ID:** FG000 **Number of Subjects:** 90 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 88 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 92 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 79 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 83 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 88 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 12 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 7 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 4 **Recruitment Details:** For this study, 47 sites were activated and screened at least 1 patient, 44 sites screened at least 1 patient who entered the run-in period, and 43 sites randomly assigned a patient. Overall, 273 patients were randomly assigned to treatment **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT06190379 **Brief Title:** Aromatherapy for Upper Respiratory Health **Official Title:** Aromatherapy for Upper Respiratory Health: A Randomized, Placebo Controlled, Triple-Blind Clinical Trial #### Organization Study ID Info **ID:** 22-12-500 #### Organization **Class:** OTHER **Full Name:** Franklin Health Research ### Status Module #### Completion Date **Date:** 2023-04-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-05 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-02-28 **Type:** ACTUAL #### Start Date **Date:** 2022-12-01 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2024-01-05 **Type:** ACTUAL **Study First Submit Date:** 2022-12-05 **Study First Submit QC Date:** 2024-01-03 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Prodeco Pharma #### Lead Sponsor **Class:** OTHER **Name:** Franklin Health Research #### 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 confirm and quantify the effects of aromatherapy on respiratory health. **Detailed Description:** Participants will inhale the scent from an aroma stick every waking hour for the entire duration of a period of respiratory symptoms or 14 days, whichever is shorter. As it is a randomized, placebo-controlled study, some participants will inhale the scent from an aroma stick containing active essential oils while other participants will inhale from an aroma stick containing no essential oils. ### Conditions Module **Conditions:** - Immune System ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 45 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Essential oil blend in an inhaler stick **Intervention Names:** - Other: Essential oil blend **Label:** Intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** blank inhaler stick **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention **Description:** an aroma stick containing a blend of essential oils **Name:** Essential oil blend **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** an aroma stick containing an inert blend of oils **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Respiratory symptoms are measured using the Franklin Immune Scale, Respiratory Subdomain, which documents the presence of over 20 symptoms, then rates them by severity. Lower scores mean lesser severity. **Measure:** severity of respiratory symptoms **Time Frame:** 14 days **Description:** Respiratory symptoms are measured daily; total number of days with symptoms will be calculated to produce a duration score **Measure:** duration of respiratory symptoms **Time Frame:** daily up to 14 days #### Secondary Outcomes **Description:** The Franklin Health Sleep Scale measures the quantity and quality of sleep across 6 subdomains. Scores are ranked on a likert scale, with higher scores indicating greater sleep quality. **Measure:** sleep scores using the Franklin Health Sleep Scale **Time Frame:** 14 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Provision of signed and dated informed consent form * Stated willingness and demonstrated ability to comply with all study procedures and availability for the duration of the study * Gender expression: female * Aged 20-65 * In good general health * Exhibiting routine upper respiratory symptoms such as: sneezing, coughing, running nose, headache, general fatigue, or dry or sore throat, etc. * Ability to utilize the inhaler and be willing to adhere to the regimen Exclusion Criteria: * Current use of bronchodilators or asthma medications * Presence of asthma diagnosis or other severe breathing disorder * Pregnant or trying to conceive * Known allergic reactions to components of the inhaler, specifically plants in the following families: rutaceae, pinaceae, labiatae, and myrtaceae. * Treatment with another investigational drug or other intervention within 30 days * Current smoker * COVID-19 diagnosis **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 20 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Franklin **Country:** United States **Facility:** Franklin Health Research **State:** Tennessee **Zip:** 37067 #### Overall Officials **Official 1:** **Affiliation:** Franklin Health Research **Name:** Jessie Hawkins, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03755479 **Brief Title:** Evaluation of Minimed 670G in T1D Patients on Multiple Daily Injection **Official Title:** Evaluation of Minimed 670G Hybrid Closed Loop System On-Boarding Protocol, for Patients With Type 1 Diabetes on Multiple Daily Insulin Injection Therapy #### Organization Study ID Info **ID:** 1810033883 #### Organization **Class:** OTHER **Full Name:** Sidra Medicine ### Status Module #### Completion Date **Date:** 2019-08-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-09-06 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-08-08 **Type:** ACTUAL #### Start Date **Date:** 2019-02-01 **Type:** ACTUAL **Status Verified Date:** 2019-09 #### Study First Post Date **Date:** 2018-11-28 **Type:** ACTUAL **Study First Submit Date:** 2018-11-25 **Study First Submit QC Date:** 2018-11-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Sidra Medicine #### Responsible Party **Investigator Affiliation:** Sidra Medicine **Investigator Full Name:** Goran Petrovski **Investigator Title:** Goran Petrovski, MD PhD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** Introduction. Sensor Augmented Pump has demonstrated superiority over insulin pump and Multiple Daily Injection (MDI) in achieving optimal glucose control and can improve quality of life in Type 1 Diabetes (T1D) patients. Hybrid closed loop (HCL) insulin pump Minimed 670G is a FDA approved device and European Conformity (CE) mark with SmartGuard technology and closed loop algorithm, which will allow the patients to improve their diabetes management. Hybrid closed loop insulin pump Minimed 670G monitors glucose in the subcutaneous tissues and automatically adjusts the delivery of rapid acting insulin as basal rate based on the user's glucose reading. SmartGuard technology in insulin pump, based on user's sensor glucose values can predict when glucose is approaching low levels, 30 minutes in advance and automatically stop insulin delivery. When user's glucose levels recover, SmartGuard will automatically resume insulin delivery. CareLink is personal software, which downloads the data from insulin pump, glucose sensor and glucometer to visualize diabetes information with charts, statistics and events that help patient and health provider to identify and understand patterns and trends The objective of this study is to assess structured group education on boarding protocol of the HCL Minimed 670 G in achieving glucose control of patients on MDI. Methods. This study is a single-arm, single-center, clinical investigation in subjects with type 1 diabetes on HCL insulin pump (Minimed 670G) in a period of 3 months. A total of 30 subjects (age 6 - 17) will be enrolled in order to reach 26 subjects who will complete the HCL study. The investigators will start the clinical process for initiating an insulin pump, which is typically done with pre-pump classes. HbA1c, derived from CGM will be performed at baseline and 3 months during the study. The following parameters will be analyzed: % patients achieving Time in Range (TIR) \> 67% from 70 mg/dl to 180 mg/dl; % patients achieving TIR \<3%, below time in range (\<70 mg/dl) and % patients achieving both TIR \> 67% and \<3% time below Range. Collection of demographics and medical history, data for diabetes devices (eg meters, sensors, pumps) and brief clinical physical exam including vital signs and skin assessment will be obtained via Hospital Electronic Medical File (Cerner Millennium, North Kansas City, US) and will be kept as electronic data on a separate research server. **Detailed Description:** This study is a single-arm, single-center, clinical investigation in subjects with Type 1 Diabetes (T1D) on Hybrid Closed Loop (HCL) insulin pump Minimed 670G in a period of 3 months. A total of 30 subjects (age 6 - 17) will be enrolled in order to reach 26 subjects who will complete the HCL study. After reviewing the patient's eligibility and interest, the investigators will obtain informed consent and assent as appropriate. The investigators will start the clinical process for initiating an insulin pump, which is typically done with pre-pump classes. HbA1c, derived from Continuous Glucose Monitoring (CGM) device will be analyzed at baseline and 3 months during the study. Collection of demographics and medical history, data for diabetes devices (eg meters, sensors, pumps) and brief clinical physical exam including vital signs and skin assessment will be obtained via Hospital Electronic Medical File (Cerner Millennium, North Kansas City) and will be kept as electronic data on a separate research server. Base line assessment The main variables checked at baseline: * Age * Duration of diabetes * Total daily insulin (TDI) dose * HbA1c, derived from CGM device Recruitment process All patients will be recruited during the regular clinic visits at Diabetes Clinics at Sidra Medicine in Doha. The Principal investigator will evaluate the patient if meets the inclusion criteria during the regular clinic visits. A research assistant will take patient and family in other room to explain the study protocol and give patient information. Parents and patients can ask questions about the study. After the explanation of the study protocol, if parents and child agree to participate, they can sign the documents for including in the study. Parents can also take the documents home to consider the possible inclusion in the study. They can also talk to principal investigator before including the child in the study. If parents agree to be a part of the study, they can call research assistant to include the child in the study. The research assistant will arrange a separate meeting to start the process. Run in period The 2-week run-in period will be used for education and training for the new devices. Week 1: Pump school (Sunday to Thursday) A group session of 2-3 patients/families will be performed to allow subject to become familiar with new insulin pump. Five sessions in a row (each two hours) will be performed during a week. Glucose sensor (Suspend before low and suspend on low will be off) will be started on the first day (Same protocol which is currently used in Sidra Medicine). Topics and education Sunday: Basal Bolus Concept; Operational modes of the pump; Understanding the pump; Pump buttons; Glucose readings; Reading the display; Sensor alerts and alarms; How to insert a sensor; Pump menus Monday: Carelink personal; Battery change; Setting date and time; Basal rates; Pump suspend; Bolus wizard, Bayer Contour Next Link 2.4 Tuesday: Infusion set change; Alarms and alerts; Suspend before low and Suspend of low; Advanced carbs counting Wednesday: Temporary basal; Emergency kit; Low blood sugar; High Blood Sugar; Sick day's management for pump; Diabetic Ketoacidosis (DKA)' Blood glucose Blood ketones; Exercise; Travel Thursday: Auto Mode; Using Auto Mode for the first time Checking Auto Mode Readiness; sensor graph in Auto Mode' Using pump in Auto Mode; Entering a Blood Glucose value in Auto Mode; Suspending and Resuming Delivery in Auto Mode Evaluation Check List; Pump Care; Setting the pump; Sensor start by patient The sensor will be started the first day for teaching and observational purposes only. CareLink account creation and sharing of access is mandatory in the first week. Week 2: Pump start (Sunday to Sunday) Sensor Augmented Pump will be initiated with both Smart Guard and HCL turned off, to allow the investigators, subjects and device to get more information before starting the HCL. This week will be used as a warm up period for Auto Mode. Study Period 3 Months Following the two week run-in period using the Minimed 670G, Auto Mode will be activated and all subjects will participate in a 3-month study period. The patient/family will upload data into the CareLink system and the data will be reviewed by a member of the clinical team. Adjustments to system settings will be suggested to the family as clinically appropriate. Visit 1- Day 1 In-Clinic visit. Insulin pump will be started in Auto mode. Carelink download for initial pump settings. HbA1c will be obtained. Visit 2- Day 3 Remote visit. Download pump at home, phone call to patient. Check the Auto Mode, pump settings and fine tune. Visit 3- Day 7 In-Clinic visit. Download pump. Check the Auto Mode, pump settings and fine tune. Visit 4- Day 14 Remote visit. Download pump at home, phone call the patient. Check the Auto Mode, pump settings and fine tune. Visit 5- Day 28 In-Clinic visit. Month 1 Download pump. Check the Auto Mode, pump settings and fine tune. Visit 6- Day 42 Remote visit. Download pump at home, phone call to patient. Check the Auto Mode, pump settings and fine tune. Visit 7- Day 84 In-Clinic visit. Month 3 Download pump. HbA1c will be obtained. Data Analysis The analysis of the main endpoint 3 month Time in Range, post intervention will be tested by the paired student t-test or paired Wilcoxon test, in case of non-normality of the end point. Evident outliers will be excluded from the main analysis but data on the complete analysis will be provided as well. The different continuous baseline values will be checked for normality of distribution using the mean-median comparison, skewness and kurtosis (-3 to +3), spread, Kolmogorov-Smirnow and Shapiro-Wild tests, outliers, histograms and Q-Q-plots. ### Conditions Module **Conditions:** - Diabetes Mellitus, Type 1 **Keywords:** - Diabetes Mellitus Type 1 - Insulin Pump - Hybrid closed Loop System - Minimed 670G ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patient on multiple daily injections will start Hybrid Closed Loop System Insulin Pump Minimed 670G **Intervention Names:** - Device: Hybrid Closed Loop Insulin Pump Minimed 670G **Label:** Single Arm Group ### Interventions #### Intervention 1 **Arm Group Labels:** - Single Arm Group **Description:** Five Day Group Education on Minimed 670G **Name:** Hybrid Closed Loop Insulin Pump Minimed 670G **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Primary outcome is to achieve glucose levels more than 67% in range between 70mg and 180 mg/dl using Minimed 670G **Measure:** Achieving glucose values more than 67% in Time in Range (70-180 mg/dl) **Time Frame:** 3 months #### Secondary Outcomes **Description:** Change in HbA1c levels from previous treatment (multiple daily injections) compared to Minimed 670G treatment **Measure:** Change in HbA1c **Time Frame:** 3 months **Description:** Percentage of glucose values more than 180 mg/dl on Minimed 670G **Measure:** Glucose values above Range (>180 mg/dl) **Time Frame:** 3 months **Description:** Percentage of time in Auto Mode, where Minimed 670G automatic adjusts the basal insulin dose according glucose levels **Measure:** Time spend in Auto Mode **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Clinical diagnosis of Type 1 Diabetes. Diagnosis of Type 1 Diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not required. 2. HbA1c \< 12.5% 3. Age 6-17 years at the initiation of the 670G system 4. Multiple Daily Injections (Basal Bolus therapy) with Total Daily Insulin use of great than 8.0 units per day over a 1 week period 5. Willing and able (access to internet from home) to download information into the Medtronic CareLink software 6. Clinically planning to and be able to start the Medtronic 670G HCL system 7. History of 3 clinic visits in the last year Exclusion Criteria: 1. DKA in the 6 months prior to screening visit **Maximum Age:** 17 Years **Minimum Age:** 6 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** Patients with Type 1 Diabetes on Multiple Daily Injections, motivated and willing to switch Hybrid Closed Loop Minimed 670G. ### Contacts Locations Module #### Locations **Location 1:** **City:** Doha **Country:** Qatar **Facility:** Sidra Medicine **State:** Qa **Zip:** 26999 #### Overall Officials **Official 1:** **Affiliation:** Sidra Medicine **Name:** Goran Petrovski, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Ly TT, Roy A, Grosman B, Shin J, Campbell A, Monirabbasi S, Liang B, von Eyben R, Shanmugham S, Clinton P, Buckingham BA. Day and Night Closed-Loop Control Using the Integrated Medtronic Hybrid Closed-Loop System in Type 1 Diabetes at Diabetes Camp. Diabetes Care. 2015 Jul;38(7):1205-11. doi: 10.2337/dc14-3073. Epub 2015 Jun 6. **PMID:** 26049550 **Citation:** Ly TT, Weinzimer SA, Maahs DM, Sherr JL, Roy A, Grosman B, Cantwell M, Kurtz N, Carria L, Messer L, von Eyben R, Buckingham BA. Automated hybrid closed-loop control with a proportional-integral-derivative based system in adolescents and adults with type 1 diabetes: individualizing settings for optimal performance. Pediatr Diabetes. 2017 Aug;18(5):348-355. doi: 10.1111/pedi.12399. Epub 2016 May 18. **PMID:** 27191182 **Citation:** de Bock MI, Roy A, Cooper MN, Dart JA, Berthold CL, Retterath AJ, Freeman KE, Grosman B, Kurtz N, Kaufman F, Jones TW, Davis EA. Feasibility of Outpatient 24-Hour Closed-Loop Insulin Delivery. Diabetes Care. 2015 Nov;38(11):e186-7. doi: 10.2337/dc15-1047. Epub 2015 Aug 27. No abstract available. **PMID:** 26316630 **Citation:** Bergenstal RM, Garg S, Weinzimer SA, Buckingham BA, Bode BW, Tamborlane WV, Kaufman FR. Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. JAMA. 2016 Oct 4;316(13):1407-1408. doi: 10.1001/jama.2016.11708. No abstract available. **PMID:** 27629148 **Citation:** Ruiz JL, Sherr JL, Cengiz E, Carria L, Roy A, Voskanyan G, Tamborlane WV, Weinzimer SA. Effect of insulin feedback on closed-loop glucose control: a crossover study. J Diabetes Sci Technol. 2012 Sep 1;6(5):1123-30. doi: 10.1177/193229681200600517. **PMID:** 23063039 **Citation:** de Bock M, Dart J, Roy A, Davey R, Soon W, Berthold C, Retterath A, Grosman B, Kurtz N, Davis E, Jones T. Exploration of the Performance of a Hybrid Closed Loop Insulin Delivery Algorithm That Includes Insulin Delivery Limits Designed to Protect Against Hypoglycemia. J Diabetes Sci Technol. 2017 Jan;11(1):68-73. doi: 10.1177/1932296816668876. Epub 2016 Sep 25. **PMID:** 27621143 **Citation:** Bailey TS, Ahmann A, Brazg R, Christiansen M, Garg S, Watkins E, Welsh JB, Lee SW. Accuracy and acceptability of the 6-day Enlite continuous subcutaneous glucose sensor. Diabetes Technol Ther. 2014 May;16(5):277-83. doi: 10.1089/dia.2013.0222. Epub 2014 Apr 7. **PMID:** 24758729 **Citation:** Tauschmann M, Allen JM, Wilinska ME, Thabit H, Acerini CL, Dunger DB, Hovorka R. Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Suboptimally Controlled Adolescents With Type 1 Diabetes: A 3-Week, Free-Living, Randomized Crossover Trial. Diabetes Care. 2016 Nov;39(11):2019-2025. doi: 10.2337/dc16-1094. Epub 2016 Sep 9. **PMID:** 27612500 ## 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 Mellitus - ID: M7117 - Name: Diabetes Mellitus, Type 1 - Relevance: HIGH - As Found: Diabetes Mellitus, Type 1 - 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 ### 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 ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: HIGH - As Found: Day 1 - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000007328 - Term: Insulin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00758979 **Brief Title:** [Trial of device that is not approved or cleared by the U.S. FDA] **Official Title:** [Trial of device that is not approved or cleared by the U.S. FDA] #### Organization Study ID Info **ID:** BMET UK 01 #### Organization **Full Name:** [Redacted] ### Status Module **Delayed Posting:** True #### Expanded Access Info #### Last Update Post Date **Date:** 2017-06-19 **Type:** ACTUAL **Last Update Submit Date:** 2017-06-16 **Overall Status:** WITHHELD #### Study First Post Date **Date:** 2008-09-25 **Type:** ESTIMATED **Study First Submit Date:** 2008-09-23 **Study First Submit QC Date:** 2008-09-23 ### Sponsor Collaborators Module #### Lead Sponsor **Name:** [Redacted] #### Responsible Party **Old Name Title:** [Redacted] **Old Organization:** [Redacted] ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06302179 **Brief Title:** Risk Factors of Venous Thromboembolism After Colorectal Cancer Surgery **Official Title:** Risk Factors of Venous Thromboembolism After Colorectal Cancer Surgery #### Organization Study ID Info **ID:** 140-14/24 #### Organization **Class:** OTHER **Full Name:** Pirogov Russian National Research Medical University ### Status Module #### Completion Date **Date:** 2023-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-08 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-12 **Type:** ACTUAL #### Start Date **Date:** 2015-01 **Type:** ACTUAL **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2024-03-08 **Type:** ACTUAL **Study First Submit Date:** 2024-03-04 **Study First Submit QC Date:** 2024-03-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Pirogov Russian National Research Medical 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:** Aim of our study is to find frequency and identify risk factors for venous thromboembolism development in patients who underwent surgery for colorectal cancer. There were 137 patients enrolled in our retrospective observational cohort study. Included patients were operated for incisional hernia in Saveljev University Surgery Clinic from January 2016 to December 2017. Compression duplex ultrasound of lower legs veins was performed in 2-14 days after surgery for all participants. The primary endpoint was the occurrence of the venous thromboembolism event, including pulmonary embolism. ### Conditions Module **Conditions:** - Colorectal Cancer - Venous Thromboembolism **Keywords:** - colorectal cancer surgery - thromboprophylaxis ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 137 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Screening ultrasound in the postoperative period was aimed at looking for signs of deep vein thrombosis. The imaged vessels included the common femoral, great saphenous, superficial femoral, deep femoral, popliteal, posterior tibial, and peroneal veins of both lower extremities. The presence of a thrombotic process in the vein was evidenced by the rigidity of its walls during compression by the sensor, the presence of hyperechoic inclusions, and the impossibility of visualizing blood flow during color mapping. **Measure:** Venous Thromboembolism **Time Frame:** was performed with median 4 days (min 2 day, max 14 days, interquartile range 2-5 days) after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: operated for incisional hernia in Saveljev University Surgery Clinic. No Exclusion Criteria **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Moscow **Country:** Russian Federation **Facility:** Pirogov Russian National Research Medical University **Zip:** 117997 ## 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 - ID: D000016769 - Term: Embolism and Thrombosis - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M16682 - Name: Thromboembolism - Relevance: HIGH - As Found: Thromboembolism - ID: M27780 - Name: Venous Thromboembolism - Relevance: HIGH - As Found: Venous Thromboembolism - 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 - ID: M16686 - Name: Thrombosis - Relevance: LOW - As Found: Unknown - ID: M7784 - Name: Embolism - 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 ### Condition Browse Module - Meshes - ID: D000015179 - Term: Colorectal Neoplasms - ID: D000013923 - Term: Thromboembolism - ID: D000054556 - Term: Venous Thromboembolism ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05269979 **Acronym:** HIP22 **Brief Title:** Hip Fracture Prevention Follow-up of Elderly Women in Primary Health Care **Official Title:** Hip Fracture Prevention by Screening and Intervention of Elderly Women in Primary Health Care. 2001 - 2022 #### Organization Study ID Info **ID:** LU40600 #### Organization **Class:** OTHER_GOV **Full Name:** Kronoberg County Council ### Status Module #### Completion Date **Date:** 2022-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2022-03-08 **Type:** ACTUAL **Last Update Submit Date:** 2022-02-25 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2005-12 **Type:** ACTUAL #### Start Date **Date:** 2001-11 **Type:** ACTUAL **Status Verified Date:** 2022-02 #### Study First Post Date **Date:** 2022-03-08 **Type:** ACTUAL **Study First Submit Date:** 2022-02-05 **Study First Submit QC Date:** 2022-02-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Kronoberg County Council #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Researchers plan a 2022 follow-up of medical records data to investigate fracture incidence and survival for 1248 women, born 1902-1931, in a comparative fracture prevention study with 435 participants from an intervention area and 813 participants from two control areas. In 2022 researchers want to assess patient records data in intervention and control areas and compare A) Survival B) Risk factors for osteoporotic fractures (wrist, upper arm, vertebral, pelvic, hip) C) physical activity, exercise and drugs that affect fracture risk. **Detailed Description:** Researchers plan a 2022 follow-up of medical records data to investigate fracture incidence and survival for 1248 women, born 1902-1931, in a comparative fracture prevention study with participants from an intervention area (Vislanda, n=435) and control areas (Emmaboda n=395 and Tingsryd (n=418). Fragility fracture prevalence after 40 years of age was 33% in the 1248 participants with mean age 79 years at baseline 2001. Participants with 2-4 risk factors (age ≥80, body weight \<60kg, previous fragility fracture or impaired rise-up ability) provided prospective data with FRAMO (FRActure and Mortality) Index as an outcome measure and this index identified 80% of hip, fragility fractures or death within a 2-year follow-up period. Hip fracture incidence 2004-2005 was not significantly lower in the intervention area but the trend of the odds ratio (0.33) was in line with significantly fewer falls and improved recovery in the intervention area. In 2022 researchers want to assess patient records data in intervention and control areas and compare A) Survival B) Risk factors for osteoporotic fractures (wrist, upper arm, vertebral, pelvic, hip) C) physical activity, exercise and drugs that affect fracture risk. Data analysis will be blinded for participation in intervention or control groups and statistical methods include Cox regression and Kaplan-Meier's survival analyzes. Birth cohort differences in outcomes will be analysed by using Lexi's diagrams. ### Conditions Module **Conditions:** - Fragility Fracture **Keywords:** - Osteoporosis ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1248 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 435 women living in Vislanda responded to a detailed survey and participated in physical exercise and received lifestyle advice on diet, smoking, walking and outdoor activities. Recommendations to use calcium and Vitamin D and do exercise at home by written instructions. Home visit by rehab team when needed. Group training with a physiotherapist. Gymnastics group and walking group. Walking aides and instructions of anti-slip protection. Home environment risk reduction was offered. **Intervention Names:** - Behavioral: Prevention of hip fractures **Label:** Intervention (the Vislanda district) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 415 women living in Tingsryd and 395 women living in Emmaboda responded to the same detailed survey as the 435 women living in Vislanda. **Label:** Control (the Tingsryd/Emmaboda districts) **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention (the Vislanda district) **Description:** Physical exercise and lifestyle advice on diet, smoking, walking and outdoor activities. Recommendations to use calcium and Vitamin D and do exercise at home by written instructions. Home visit by rehab team when needed. Group training with a physiotherapist. Gymnastics group and walking group. Walking aides and instructions of anti-slip protection. Home environment risk reduction was offered. **Name:** Prevention of hip fractures **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Days **Measure:** Survival **Time Frame:** Maximum 21 years of follow up (Participants were on average 79 years old (70 to 100 years) at study start) **Description:** Dates **Measure:** Fragility fractures **Time Frame:** Maximum 21 years follow up **Description:** Dates **Measure:** Hip fractures **Time Frame:** Maximum 21 years follow up #### Secondary Outcomes **Description:** Days **Measure:** Time from fragility fractures until death **Time Frame:** Maximum 21 years follow up ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Invitation letter was sent out to all women in three predefined geographical areas of south Sweden born 1902-1931 Exclusion Criteria: Participants who themselves or their significant others did not read or understand Swedish were excluded. **Healthy Volunteers:** True **Maximum Age:** 100 Years **Minimum Age:** 70 Years **Sex:** FEMALE **Standard Ages:** - OLDER_ADULT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014947 - Term: Wounds and Injuries - ID: D000005264 - Term: Femoral Fractures - ID: D000025981 - Term: Hip Injuries - ID: D000007869 - Term: Leg Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M26370 - Name: Fractures, Bone - Relevance: HIGH - As Found: Fracture - ID: M9696 - Name: Hip Fractures - Relevance: HIGH - As Found: Hip Fracture - ID: M12947 - Name: Osteoporosis - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M8402 - Name: Femoral Fractures - Relevance: LOW - As Found: Unknown - ID: M23105 - Name: Hip Injuries - Relevance: LOW - As Found: Unknown - ID: M10881 - Name: Leg Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000050723 - Term: Fractures, Bone - ID: D000006620 - Term: Hip Fractures ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: LOW - As Found: Unknown - ID: M6003 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: M5381 - Name: Calcium - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05524779 **Brief Title:** BTL-785F Device for Non-invasive Reduction of Wrinkles and Overall Facial Improvement **Official Title:** Evaluation of Safety and Efficacy of the BTL-785F Device for Non-invasive Reduction of Wrinkles and Overall Improvement of Appearance of the Face #### Organization Study ID Info **ID:** BTL-785_CTUS1300 #### Organization **Class:** INDUSTRY **Full Name:** BTL Industries Ltd. ### Status Module #### Completion Date **Date:** 2023-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-09-06 **Type:** ACTUAL **Last Update Submit Date:** 2022-09-01 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2023-04 **Type:** ESTIMATED #### Start Date **Date:** 2022-09 **Type:** ESTIMATED **Status Verified Date:** 2022-09 #### Study First Post Date **Date:** 2022-09-01 **Type:** ACTUAL **Study First Submit Date:** 2022-08-30 **Study First Submit QC Date:** 2022-08-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** BTL Industries Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will evaluate the clinical safety and the performance of the BTL-785F system equipped with the BTL-785-7 applicator for non-invasive treatment of facial wrinkles. **Detailed Description:** The study is a multicenter single-arm, open-label, interventional study. The subjects will be enrolled and assigned into one experimental study arm. The subjects will be required to complete four (4) treatment visits and two follow-up visits. At the baseline visit health status will be assessed and, if needed, additional tests will be performed. Inclusion and exclusion criteria will be verified and informed consent will be signed. The treatment administration phase consists of four (4) treatment visits, delivered 5-10 days apart. Safety measures will include documentation of adverse events (AE) including the subject's experience of pain or discomfort after the procedure. Occurrence of AE's will be checked immediately after the first treatment visit, prior/post to the every other procedure and at the follow-ups. Subjects will undergo two follow-up visits scheduled at 1 month and 3 months after the final treatment. ### Conditions Module **Conditions:** - Wrinkle ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Treatment of wrinkles with the BTL-785-7 applicator to the BTL-785F system. **Intervention Names:** - Device: BTL-785-7 **Label:** BTL-785-7 Treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - BTL-785-7 Treatment **Description:** Treatment with the BTL-785-7 applicator to the BTL-785F system. **Name:** BTL-785-7 **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Assess change in wrinkle severity according to the Fitzpatrick Wrinkle and Elastosis Scale. Baseline and post-treatment photographs will be evaluated. A statistically significant decrease of at least 1.0 score in the average score of Fitzpatrick Wrinkle and Elastosis Scale should be achieved. **Measure:** Noninvasive Treatment Of Wrinkles **Time Frame:** 5 months #### Secondary Outcomes **Description:** Three evaluators will evaluate facial appearance according to the Global Aesthetic Improvement Scale (GAIS) using the photographs taken at the baseline, last therapy visit and both follow-up visits. Each evaluator will be asked to assign a score to a set of photographs. Facial appearance improvement to GAIS is considered when there is an increase in score of the scale. The baseline and post-treatment scores will be compared. If applicable, the statistical significance of obtained results will be analyzed in Microsoft Excel spreadsheet software. The level of significance (α) will be set as 5%. **Measure:** Skin Quality Assessment **Time Frame:** 5 months **Description:** The 5-point Likert scale Therapy Comfort questionnaire will be used for evaluating the comfort during the treatment sessions. Pain sensation will be rated by the subjects from 0 (no pain) to 10 (worst possible pain). **Measure:** Therapy Comfort **Time Frame:** 5 months **Description:** The Subject Satisfaction questionnaire will be used for evaluating the satisfaction. The Subject Satisfaction Questionnaire will be given to subjects after the last treatment, at 1-month and 3-month follow-up. The answers to the questions related to the subjects' overall skin and face appearance will vary from "strongly agree" to "strongly disagree". **Measure:** Subject Satisfaction **Time Frame:** 5 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy male or female subjects over 21 years of age seeking treatment for reduction of wrinkles and overall aesthetic improvement of the face * Subjects should be able understand the investigative nature of the treatment, the possible benefits and side effects, and must sign the Informed Consent Form * Presence of clearly visible wrinkles in the treated area when the face is relaxed as deemed appropriate by the Investigator * Subjects willing and able to abstain from partaking in any facial treatments other than the study procedure during study participation * Willingness to comply with study instructions, to return to the clinic for the required visits, and to have photographs of their face taken Exclusion Criteria: * Bacterial or viral infection, acute inflammations * Impaired immune system * Isotretinoin in the past 12 months * Skin related autoimmune diseases * Radiation therapy and chemotherapy * Poor healing and unhealed wounds in the treatment area * Metal implants * Permanent implant in the treated area * Pacemaker or internal defibrillator, or any other active electrical implant anywhere in the body * Facial dermabrasion, facial resurfacing, or deep chemical peeling in the treatment area within 3 months prior to the treatment * Current or history of skin cancer, or current condition of any other type of cancer, or pre-malignant moles * History of any type of cancer * Active collagen diseases * Cardiovascular diseases (such as vascular diseases, peripheral arterial disease, thrombophlebitis and thrombosis) * Pregnancy/nursing or IVF procedure * History of bleeding coagulopathies, use of anticoagulants * Any active condition in the treatment area, such as sores, psoriasis, eczema, rash and rosacea * Any surgical procedure in the treatment area within the last three months or before complete healing * Poorly controlled endocrine disorders, such as diabetes * Electroanalgesia without exact diagnosis of pain etiology * Application in the area of chest, heart or over the eyes * Serious psychopathological disorders (such as schizophrenia) * Neurological disorders (such as multiple cerebrospinal sclerosis, epilepsy) * Blood vessels and lymphatic vessels inflammation **Healthy Volunteers:** True **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Gilbert **Country:** United States **Facility:** Contour Medical **State:** Arizona **Zip:** 85297 **Location 2:** **City:** San Marcos **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Amanda Holden, MD - **Phone:** 760-338-0796 - **Role:** CONTACT ***Contact 2:*** - **Name:** Amanda Holden, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Holden Timeless Beauty **State:** California **Zip:** 92069 **Location 3:** **City:** Davie **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Lesley Clark-Loeser, MD - **Phone:** 954-998-0345 - **Role:** CONTACT ***Contact 2:*** - **Name:** Lesley Clark-Loeser, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Precision Skin Institute **State:** Florida **Zip:** 33328 **Location 4:** **City:** Macon **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** David Kent, MD - **Phone:** 478-742-2180 - **Role:** CONTACT ***Contact 2:*** - **Name:** David Kent, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Skin Care Physicians of Georgia **State:** Georgia **Zip:** 31217 **Location 5:** **City:** New York **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Jennifer Levine, MD - **Phone:** 646-362-5245 - **Role:** CONTACT ***Contact 2:*** - **Name:** Jennifer Levine, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Jennifer Levine MD **State:** New York **Zip:** 10075 ### IPD Sharing Statement Module **IPD Sharing:** NO ## 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: M21089 - Name: Facies - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02732379 **Brief Title:** Effect of Aromatherapy on Postoperative Nausea, Vomiting **Official Title:** Evaluating the Efficacy of Aromatherapy on Postoperative Nausea, Vomiting #### Organization Study ID Info **ID:** PONV #### Organization **Class:** OTHER **Full Name:** Tokat Gaziosmanpasa University ### Status Module #### Completion Date **Date:** 2018-11-14 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-12-04 **Type:** ACTUAL **Last Update Submit Date:** 2018-12-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-11-13 **Type:** ACTUAL #### Start Date **Date:** 2016-04 **Status Verified Date:** 2018-12 #### Study First Post Date **Date:** 2016-04-08 **Type:** ESTIMATED **Study First Submit Date:** 2016-03-30 **Study First Submit QC Date:** 2016-04-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Tokat Gaziosmanpasa University #### Responsible Party **Investigator Affiliation:** Tokat Gaziosmanpasa University **Investigator Full Name:** Tuğba Karaman **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of this study is to evaluate the effect of the aromatherapy with lavender, rose or ginger essential oils on nausea, vomiting and postoperative quality of recovery scores in patients with postoperative nausea and vomiting. **Detailed Description:** Postoperative Nausea and Vomiting (PONV) relief is still challenge for the anesthesiologist. Pharmacological therapies is also cornerstone for treatment of PONV. Although future researches are needed, there is some proofs about the aromatherapy could provide an inexpensive, noninvasive and effective treatment for PONV. ### Conditions Module **Conditions:** - Postoperative Nausea and Vomiting **Keywords:** - Postoperative Nausea and Vomiting - Aromatherapy - Quality of Health Care ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 184 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Aromatherapy with lavender essential oil. **Intervention Names:** - Procedure: Lavender Aromatherapy **Label:** Lavender Aromatherapy **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Aromatherapy with rose essential oil **Intervention Names:** - Procedure: Rose Aromatherapy **Label:** Rose Aromatherapy **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Aromatherapy with ginger essential oil **Intervention Names:** - Procedure: Ginger Aromatherapy **Label:** Ginger Aromatherapy **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Aromatherapy with pure water **Intervention Names:** - Procedure: Placebo Aromatherapy **Label:** Placebo Aromatherapy **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Lavender Aromatherapy **Description:** the two drops of lavender essential oil will be dropped into the gauze and the patient will inhale it for 5 minutes. **Name:** Lavender Aromatherapy **Other Names:** - Aromatherapy with lavender essential oil **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Rose Aromatherapy **Description:** the two drops of rose essential oil will be dropped into the gauze and the patient will inhale it for 5 minutes. **Name:** Rose Aromatherapy **Other Names:** - Aromatherapy with rose essential oil **Type:** PROCEDURE #### Intervention 3 **Arm Group Labels:** - Ginger Aromatherapy **Description:** the two drops of ginger essential oil will be dropped into the gauze and the patient will inhale it for 5 minutes. **Name:** Ginger Aromatherapy **Other Names:** - Aromatherapy with ginger essential oil **Type:** PROCEDURE #### Intervention 4 **Arm Group Labels:** - Placebo Aromatherapy **Description:** the two drops of pure water will be dropped into the gauze and the patient will inhale it for 5 minutes **Name:** Placebo Aromatherapy **Other Names:** - Aromatherapy with pure water **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Nausea will be measured with verbal descriptive scale on 0 to 3 Likert-type scale(0=no nausea, 1=some, 2= a lot, 3= severe) **Measure:** The change of the nausea scores **Time Frame:** During postoperative 24 hours **Description:** Vomiting will be measured with verbal descriptive scale (0=no vomiting, 1= 1 time, 2= 2 or 3 times, 3= 4 times and up) **Measure:** The change of the vomiting score **Time Frame:** During postoperative 24 hours #### Secondary Outcomes **Description:** The antiemetic drug dose will be recorded **Measure:** The consumption of the antiemetic drug **Time Frame:** During postoperative 24 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria : * Be scheduled for elective surgery * Have a postoperative nausea and vomiting Exclusion Criteria: * Age \> 65years or \<18 years * Not accepted to inhale lavender, rose or ginger oil * Preoperative predications with anti emetic drugs * Pregnancy or breastfeeding * Asthma, Chronic obstructive pulmonary disease * Poor sense of smell * Allergy to the lavender, rose or ginger oil **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tokat **Country:** Turkey **Facility:** Gaziosmanpasa University Medical School Hospital **Zip:** 60100 #### Overall Officials **Official 1:** **Affiliation:** Gaziosmanpasa University **Name:** Tugba Karaman, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012817 - Term: Signs and Symptoms, Digestive - ID: D000011183 - Term: Postoperative Complications - 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: M12273 - Name: Nausea - Relevance: HIGH - As Found: Nausea - ID: M17582 - Name: Vomiting - Relevance: HIGH - As Found: Vomiting - ID: M22074 - Name: Postoperative Nausea and Vomiting - Relevance: HIGH - As Found: Postoperative Nausea - ID: M15622 - Name: Signs and Symptoms, Digestive - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009325 - Term: Nausea - ID: D000014839 - Term: Vomiting - ID: D000020250 - Term: Postoperative Nausea and Vomiting ### Intervention Browse Module - Browse Branches - Abbrev: HB - Name: Herbal and Botanical - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T166 - Name: Ginger - Relevance: HIGH - As Found: Exertion - ID: T141 - Name: English Lavender - Relevance: HIGH - As Found: Termination ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05178979 **Brief Title:** A Gender Transformative Implementation Strategy With Providers to Improve HIV Outcomes in Uganda **Official Title:** A Gender Transformative Implementation Strategy With Providers to Improve HIV #### Organization Study ID Info **ID:** K01MH121663-01A1 **Link:** https://reporter.nih.gov/quickSearch/K01MH121663-01A1 **Type:** NIH #### Organization **Class:** OTHER **Full Name:** The University of Texas at San Antonio #### Secondary ID Infos **ID:** 1K01MH121663-01A1 **Link:** https://reporter.nih.gov/quickSearch/1K01MH121663-01A1 **Type:** NIH ### Status Module #### Completion Date **Date:** 2023-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-01-05 **Type:** ACTUAL **Last Update Submit Date:** 2023-01-04 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-12-31 **Type:** ACTUAL **Status Verified Date:** 2023-01 #### Study First Post Date **Date:** 2022-01-05 **Type:** ACTUAL **Study First Submit Date:** 2021-11-15 **Study First Submit QC Date:** 2022-01-04 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Makerere University **Class:** NIH **Name:** National Institute of Mental Health (NIMH) #### Lead Sponsor **Class:** OTHER **Name:** The University of Texas at San Antonio #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Gender norms embedded in the health-system and broader community shape patient-provider relationships in ways that may undermine the provision of antiretroviral treatment (ART) counseling for men and women in Uganda. This study seeks to develop and evaluate the acceptability, feasibility, and preliminary efficacy of an innovative gender transformative implementation strategy to improve HIV provider capacity for equitable HIV care and ART adherence counseling. **Detailed Description:** Antiretroviral treatment (ART) is the single most effective clinical intervention in the fight against HIV. However, in Uganda only 56% of people living with HIV were virally suppressed in 2017 with significant disparities between men and women, suggesting problems with implementation. While gender norms are a known driver of HIV disparities in sub-Saharan Africa, and patient-provider relationships are a key factor in HIV care engagement, little research has focused on the role that gender norms have in shaping the equitable provision of treatment and quality of ART counseling. The overall research objective is to develop and pilot test an implementation strategy to increase providers' capacity to provide equitable and gender-tailored treatment and counseling to HIV-infected men and women. Delivered to HIV providers, this group training integrates a gender transformative approach with adapted evidence-based strategies to reduce biases and increase gender equitable attitudes. The pilot trial will assess the implementation strategy's effectiveness by comparing changes in provider (competence for gender sensitive care) and in patient outcomes (clinic attendance, ART adherence, viral load) between the training intervention and usual care through 12-months. The implementation strategy will be assessed through a quasi-experimental pre/post design. Clinics will be randomly assigned to either the intervention or control condition. Providers in the intervention condition will receive a series of group training sessions. All participants in the provider cohort will complete interviewer administered questionnaires at baseline, 6-, and 12- month follow-up. In addition to the assessment of the cohort of HIV providers, the study will obtain additional data on the impact of the provider training on patient outcomes. Patient participants will complete an interviewer administered questionnaire at baseline, 6-, and 12- month follow-up, and will provide permission for the study team to review and extract relevant data from their clinic records related to engagement in HIV care. The total N and primary outcomes reflected in the clinicaltrials.gov database reflects the patient cohort (N=240, 120 per treatment arm). Secondary outcomes are obtained from the provider cohort (n=20-35 providers per clinic). ### Conditions Module **Conditions:** - HIV ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Clinics will be randomly assigned to intervention or control via coin toss. Two cohorts of participants will be recruited from both the intervention arm and control arm. The total number of participants (N=240) represents the patient cohort, for which change in patient HIV engagement outcomes are the primary outcomes of the study. A second cohort of HIV providers will also be recruited (n\~80-140) depending on the number of HIV providers per clinic, who will provide secondary outcomes related to change in provider knowledge, attitudes, and skills. ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 383 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The intervention arm will receive up to 4 sessions of training. Trained intervention facilitator experienced in health professional trainings will lead the training. The intervention content delivered is aimed to increase HIV providers' knowledge, motivation, skills, and empathy to: 1) equitably deliver ART program guidelines (i.e., quality of care) and 2) provide gender sensitive counseling to address ART patients' gendered barriers to HIV care engagement, increasing patient satisfaction, retention, and ART adherence, and reducing gender disparities in HIV outcomes. **Intervention Names:** - Behavioral: Training **Label:** Intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The control arm will receive no training. **Label:** Control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention **Description:** This training program integrates evidence-based strategies to reduce provider bias, adapted to address gender bias in the context of HIV care in Uganda. The content aims to increase providers' knowledge, motivation, skills, and empathy to equitably deliver Ugandan Ministry of Health ART program guidelines to male and female patients (e.g., increasing awareness of HIV gender disparities, increasing empathy/skills to counsel men and women's gendered barriers to care, promoting shared decision-making). The intervention is delivered in a series of group training sessions with HIV providers. **Name:** Training **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** AACTG Adherence Instruments, self-reported questionnaire on medication adherence from the Adult AIDS Clinical Trials Group (AACTG); operationalized as a proportion of total missed doses (missed doses/total doses) (continuous measure, range =0.0-1.0) **Measure:** Change in proportion of missed antiretroviral (ARV) doses from baseline among patients **Time Frame:** 6-months **Description:** AACTG Adherence Instruments, self-reported questionnaire on medication adherence from the Adult AIDS Clinical Trials Group (AACTG); operationalized as a proportion of total missed doses (missed doses/total doses) (continuous measure, range =0.0-1.0) **Measure:** Change in proportion of missed ARV doses from baseline among patients **Time Frame:** 12-months **Description:** AACTG Adherence Instruments, self-reported questionnaire on medication adherence from the Adult AIDS Clinical Trials Group (AACTG); operationalized as having taken 90% of doses as prescribed in the reporting period (dichotomous measure: 0 not adherent; 1 adherent) **Measure:** Change in antiretroviral treatment (ART) adherence (90% of doses taken as prescribed) from baseline among patients **Time Frame:** 6-months **Description:** AACTG Adherence Instruments, self-reported questionnaire on medication adherence from the Adult AIDS Clinical Trials Group (AACTG); operationalized as having taken 90% of doses as prescribed in the reporting period (dichotomous measure: 0 not adherent; 1 adherent) **Measure:** Change in ART adherence (90% of doses taken as prescribed) from baseline among patients **Time Frame:** 12-months **Description:** Number of missed visits accrued based on scheduled visits determined by Ministry of Health clinical guidelines, collected through clinic records **Measure:** Change in number of missed visits accrued (count measure) from baseline among patients **Time Frame:** 6-months **Description:** Number of missed visits accrued based on scheduled visits determined by Ministry of Health clinical guidelines, collected through clinic records **Measure:** Change in number of missed visits accrued (count measure) from baseline among patients **Time Frame:** 12-months **Description:** Proportion of kept visits/scheduled visits (kept + missed visits) (continuous measure, range =0.0-1.0) **Measure:** Change in clinic visit adherence from baseline among patients **Time Frame:** 6-months **Description:** Proportion of kept visits/scheduled visits (kept + missed visits) (continuous measure, range =0.0-1.0) **Measure:** Change in clinic visit adherence from baseline among patients **Time Frame:** 12-months #### Secondary Outcomes **Description:** Viral load **Measure:** Change in viral load from baseline to 12 months follow-up among patients **Time Frame:** 12-months **Description:** Adapted from Consumer Satisfaction Survey and User's Manual, self-reported questionnaire, using version previously adapted for HIV populations - Total possible score using mean scoring: 0-4 (high score = better outcome) **Measure:** Change in overall satisfaction with HIV clinical care from baseline among patients **Time Frame:** 6-months **Description:** Adapted from Consumer Satisfaction Survey and User's Manual, self-reported questionnaire, using version previously adapted for HIV populations - Total possible score using mean scoring: 0-4 (high score = better outcome) **Measure:** Change in overall satisfaction with HIV clinical care from baseline among patients **Time Frame:** 12-months **Description:** Adapted from the Nijmegen Gender Awareness in Medicine Scale (N-GAMS); collected from provider cohort; 9 items, total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in gender awareness from baseline among providers **Time Frame:** 6-months **Description:** Adapted from the Nijmegen Gender Awareness in Medicine Scale (N-GAMS); collected from provider cohort; 9 items, total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in gender awareness from baseline among providers **Time Frame:** 12-months **Description:** Awareness of societal gender inequities in the provider cohort, adapted to be specific to gender from the Self-Rated Cultural Competence Instrument for Primary Care Providers Total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in awareness of gender disparities in HIV care from baseline among providers **Time Frame:** 6-months **Description:** Awareness of societal gender inequities in the provider cohort, adapted to be specific to gender from the Self-Rated Cultural Competence Instrument for Primary Care Providers 5-items; total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in awareness of gender inequities from baseline among providers **Time Frame:** 12-months **Description:** Perceived importance of providing gender sensitive counseling in the provider cohort, adapted to be specific to gender from the Self-Rated Cultural Competence Instrument for Primary Care Providers Total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in perceived importance of gender sensitive counseling from baseline among providers **Time Frame:** 6-months **Description:** Perceived importance of providing gender sensitive counseling in the provider cohort, adapted to be specific to gender from the Self-Rated Cultural Competence Instrument for Primary Care Providers Total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in perceived importance of gender sensitive counseling from baseline among providers **Time Frame:** 12-months **Description:** Self-reported change in gender sensitive counseling skills and behaviors in the provider cohort, adapted to be specific to gender from the Self-Rated Cultural Competence Instrument for Primary Care Providers Total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in gender sensitive counseling skills from baseline among providers **Time Frame:** 6-months **Description:** Self-reported change in gender sensitive counseling skills and behaviors in the provider cohort, adapted to be specific to gender from the Self-Rated Cultural Competence Instrument for Primary Care Providers Total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in gender sensitive counseling skills from baseline among providers **Time Frame:** 12-months **Description:** Self-reported change in self-efficacy to provide gender sensitive patient-centered communication in the provider cohort, adapted to be specific to gender from the Self Efficacy Questionnaire (SE-12) Total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in self-efficacy for gender specific provider communication from baseline among providers **Time Frame:** 6-months **Description:** Self-reported change in self-efficacy to provide gender sensitive patient-centered communication in the provider cohort, adapted to be specific to gender from the Self Efficacy Questionnaire (SE-12) Total possible score using mean scoring: 1-5 (high score = better outcome) **Measure:** Change in self-efficacy for gender specific provider communication from baseline among providers **Time Frame:** 12-months **Description:** Self-reported attitudes towards gender equity measured with the Gender Equitable Men scale Total possible score using mean scoring: 1-3 (high score = worse outcome) **Measure:** Change in Gender Equitable Norms from baseline among providers **Time Frame:** 6-months **Description:** Self-reported attitudes towards gender equity measured with the Gender Equitable Men scale Total possible score using mean scoring: 1-3 (high score = worse outcome) **Measure:** Change in Gender Equitable Norms from baseline among providers **Time Frame:** 12-months ### Eligibility Module **Eligibility Criteria:** Provider Cohort: Inclusion Criteria: * HIV care provider at the selected clinics, including HIV medical and clinical officers, nurses, midwives, linkage facilitators, counselors. * 18 years of age or older * Fluent in English or Luganda Patient Cohort: Inclusion Criteria: * HIV-infected * Enrolled in care at the clinic of recruitment * pre-ART (newly diagnosed) or newly initiated on ART (within 3 months-1 year) or struggling with treatment adherence, defined in two ways: (1) most recent viral load results unsuppressed as assessed through clinic records; (2) or self-reported non-adherence as by the Adult AIDS Clinical Trials Group (AACTG) scale 4-day adherence recall questions. This scale has demonstrated good construct validity in Uganda and strong correlations with viral load; * 18 years of age or an emancipated minor * Fluent in Luganda or English **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Luwero **Country:** Uganda **Facility:** Luwero Health HCIV **Location 2:** **City:** Namayumba **Country:** Uganda **Facility:** Namayumba Health HCIV #### Overall Officials **Official 1:** **Affiliation:** University of Texas at San Antonio **Name:** Katelyn M Sileo, PhD, MPH **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Makerere School of Pubic Health **Name:** Rhoda K. Wanyenze, MBChB, MPH, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Upon request from the PI **Description:** Quantitative data collected in this trial (baseline, follow-up assessments) will be made available, under the following provisions: (1)The data will be fully de-identified; (2) Access to the data will be made available first to researchers and their students at the two collaborating institutions (within 3 years of study completion): The University of Texas at San Antonio and the Makerere University School of Public Health (MakSPH); 3) 5 years after study completion, data will be made available to those requesting access outside of the collaborating institutions. Qualitative data collected as part of this trial will not be made available, as it is difficult to fully de-identify and to interpret without knowledge of the context. **Info Types:** - STUDY_PROTOCOL - SAP - ICF **IPD Sharing:** YES **Time Frame:** 3 years after study completion for researchers and students within the collaborating institutions and 5 years after study completion for those outside of the collaborating institutions upon request ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05429879 **Brief Title:** The Impact of Music on Pain and Anxiety During Flexible Cystoscopies **Official Title:** The Impact of Music on Pain and Anxiety During Flexible Cystoscopies: A Comparison Between the Patient's Preferred Music, Classical Music, and the Absence of Music #### Organization Study ID Info **ID:** 101548 #### Organization **Class:** OTHER **Full Name:** Horizon Health Network ### Status Module #### Completion Date **Date:** 2024-05-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-14 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-12 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-05-30 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-23 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2022-06-23 **Type:** ACTUAL **Study First Submit Date:** 2022-05-26 **Study First Submit QC Date:** 2022-06-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Dalhousie University #### Lead Sponsor **Class:** OTHER **Name:** Horizon Health Network #### Responsible Party **Investigator Affiliation:** Horizon Health Network **Investigator Full Name:** Gavin Langille **Investigator Title:** Staff Urologist **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Background: Cystoscopy is a routine diagnostic test often performed in the outpatient Urology setting. However, patients may sometimes feel pain and anxiety during this procedure. Distraction therapies, including patient preferred music and classical music may reduce pain and anxiety associated with cystoscopy. However, it is unclear if patient preferred music has greater positive outcomes for patients than classical music. Hypothesis: We hypothesize that patient preferred music during flexible cystoscopies will reduce patient self-reported pain and anxiety scores when compared to classical music and absence of music. Objective: To assess whether a patient's preferred music reduces pain and anxiety during cystoscopies when compared to classical music and the absence of music Methods: This is a prospective randomized control study where patients undergoing flexible cystoscopy in the outpatient Urology clinic will be randomly assigned to one of three groups: Preferred music, classical music, or no music for their procedure. Differences in pain and anxiety will be assessed between groups using the Visual Analog Scale and State-Trait Anxiety Inventory scale. Potential Benefits: Identifying and understanding non-pharmacological interventions that can reduce pain and anxiety during cystoscopies is an important task that will allow urologists to better manage these patients. **Detailed Description:** Previous studies have shown that using music as a non-pharmacological intervention is an effective, safe, and inexpensive way to address pain and anxiety in patients during cystoscopies. However few studies have compared patient outcomes between preferred music and classical music groups, and no studies have compared these groups in a North American sample population. The intent of this project is to compare pain and anxiety in those listening to their preferred music, classical music, and no music during their cystoscopy to assess what might be the optimal way to provide this non-pharmacological intervention. Identifying and understanding non-pharmacological interventions that can reduce pain and anxiety during cystoscopies is an important task that will allow urologists to better manage these patients. The purpose of this study is to assess the impact of a patient's preferred choice of music on pain and anxiety when compared to classical music and the absence of music. The study design will included a 1:1:1 randomization with equal group membership performed for both male and female sexes. Group 1 will allow patients to listen to their preferred music choice during cystoscopy, group 2 will listen to a standardized copyright free playlist of classical music, and group 3 will listen to no music and serve as a control group. Patients will be recruited and consented on the day of the procedure prior to filling out the State Trait Anxiety Inventory (STAI) questionnaire. After their procedure, patients will fill out the STAI questionnaire; Visual Analog Scales (VAS) for pain, satisfaction, and discomfort; and Likert scales for patients to rate their music experience. Music, when present, will be delivered via a speaker system allowing for communication between the urologist and the patient during the procedure. Only one urologist will be performing all flexible cystoscopies. Aside from the addition of music therapy for groups 1 and 2, standard of care will not be impacted. Statistical analysis will be conducted by two-way ANCOVA comparing the mean of quantitative outcome variables between the three music groups and each sex. In the event of a significant interaction between the music and sex variables, one way-ANCOVA will be performed within each sex, followed by Bonferroni-corrected post-hoc tests. All data will be collected and stored appropriately as according to institutional policies as well as any relevant chapters and sections of TCPS2. Power analysis was performed to estimate the minimum sample size required to conduct the proposed ANCOVA analyses. A review of relevant literature indicated effect sizes ranging from small to large for both VAS and STAI scores. We therefore estimated our sample size using a medium effect size to provide a reasonable common ground among findings in the literature. Due to the 1:1:1 design for both sexes, we will target a sample size of 162 to allow for an equal allocation of 27 participants per group. ### Conditions Module **Conditions:** - Flexible Cystoscopy **Keywords:** - Flexible cystoscopy - Music therapy - Urology - Anxiety - Pain - Satisfaction - Discomfort - Preferred music - Classical music ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** This is a prospective randomized control study that is designed to study outcomes between subjects. Participants will be randomly assigned to one of three groups and will be stratified according to sex. Stratified randomization will be done by selection of sequential pre-filled envelopes containing the group for a particular patient at the time of cystoscopy - This is a 1:1:1 randomization with equal group membership performed for both male and female sexes - The envelopes will be randomized by pre-assigning an order of participants to each of the three groups within each sex using a Random sequence generator. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 162 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This arm will allow patients to listen to their preferred music choice during their cystoscopy. **Intervention Names:** - Other: Preferred Music Arm **Label:** Preferred Music Arm **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients will listen to a standard playlist of copyright free classical music. **Intervention Names:** - Other: Classical Music Arm **Label:** Classical Music Arm **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Patients will not listen to music during cystoscopy. **Label:** No music Arm **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Preferred Music Arm **Description:** Patients will choose their preferred music to be played during the cystoscopy procedure. No music will be played prior to or immediately after the flexible cystoscopy procedure. Music will be delivered via a speaker allowing for communication between the urologist and the patient during the procedure. Aside from addition of music, standard of care will not be impacted. **Name:** Preferred Music Arm **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Classical Music Arm **Description:** A standardized playlist of copyright free classical music will be played during the cystoscopy procedure. No music will be played prior to or immediately after the flexible cystoscopy procedure. Music will be delivered via a speaker allowing for communication between the urologist and the patient during the procedure. Aside from addition of music, standard of care will not be impacted. **Name:** Classical Music Arm **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Anxiety score is measured using the State Trait Anxiety Inventory (STAI). The STAI consists of two questionnaires that classifies a patient's anxiety into three groups on a scale of 20 to 80. The STAI includes two component questionnaires known as State Anxiety and Trait Anxiety. Trait Anxiety corresponds with stable individual anxiety measures while State Anxiety refers to anxiety that an individual is experiencing at a specific given moment at time. As described by the State-Trait Anxiety Inventory for Adults manual, people with higher Trait Anxiety measures may have elevated State Anxiety measures as compared to people with lower Trait Anxiety. In our study, Trait Anxiety will be controlled for, since differences in Trait Anxiety may confound State Anxiety measurements due to the individual being naturally more anxious due to unrelated reasons. A higher STAI anxiety score indicates higher anxiety. **Measure:** Post-Cystoscopy Anxiety Score **Time Frame:** Immediately after the procedure **Description:** The delta State Trait Anxiety Inventory (delta STAI) is a measure of the change in STAI anxiety score immediately after the cystoscopy minus STAI anxiety score immediately prior to the cystoscopy. The delta STAI ranges on a scale from negative 60 to positive 60. A positive delta STAI score indicates that there was a greater STAI anxiety score immediately after the procedure as compared to immediately before the procedure. A higher positive delta STAI score means a greater increase in anxiety as compared to a lower delta STAI score. A negative delta STAI score indicates that there was a lower STAI anxiety score immediately after the procedure as compared to immediately before the procedure. A more negative delta STAI score indicates a greater decrease in anxiety as compared to a less negative delta STAI score. A delta STAI score of 0 indicates that there was no change in STAI anxiety score from immediately before the procedure to immediately after the procedure. **Measure:** Change in Anxiety Score from immediately before to immediately after cystoscopy (delta STAI) **Time Frame:** Change from immediately before the procedure to immediately after the procedure **Description:** Pelvic pain will be measured using a Visual Analog Scale (VAS). The VAS score is completed by the patient ranking their pain intensity on 10-cm lines and providing a range of scores from 0 to 100. This measure is then converted to a score of 10 (to 1 decimal eg. 8.2/10). For this study, VAS scales will be filled out by the patient immediately following their cystoscopy. A higher VAS score indicates greater self reported pelvic pain. **Measure:** Pelvic pain score **Time Frame:** Immediately after the procedure #### Secondary Outcomes **Description:** Pelvic discomfort will be measured using a Visual Analog Scale (VAS). The VAS score is completed by the patient ranking their discomfort on 10-cm lines and providing a range of scores from 0 to 100. This measure is then converted to a score of 10 (to 1 decimal eg. 8.2/10). For this study, VAS scales will be filled out in the post-procedure questionnaire by the patient immediately following their cystoscopy. A higher VAS score indicates greater self reported pelvic discomfort. **Measure:** Pelvic discomfort score **Time Frame:** Immediately after the procedure **Description:** Patient satisfaction with cystoscopy will be measured using a Visual Analog Scale (VAS). The VAS score is completed by the patient ranking their satisfaction on 10-cm lines and providing a range of scores from 0 to 100. This measure is then converted to a score of 10 (to 1 decimal eg. 8.2/10). For this study, VAS scales will be filled out in the post-procedure questionnaire by the patient immediately following their cystoscopy. A higher VAS score indicates greater self reported patient satisfaction. **Measure:** Patient satisfaction score **Time Frame:** Immediately after the procedure **Description:** Willingness to repeat cystoscopy will be measured using a Visual Analog Scale (VAS). The VAS score is completed by the patient ranking their willingness to repeat cystoscopy on 10-cm lines and providing a range of scores from 0 to 100. This measure is then converted to a score of 10 (to 1 decimal eg. 8.2/10). For this study, VAS scales will be filled out in the post-procedure questionnaire by the patient immediately following their cystoscopy. A higher VAS score indicates greater willingness to repeat cystoscopy. **Measure:** Willingness to repeat cystoscopy score **Time Frame:** Immediately after the procedure **Description:** How pleasant patients found the music during their cystoscopy will be measured using a 5-point Likert scale where patients rate their agreement with the statement "I found the music pleasant". Ratings include "Strongly agree, Agree, Neither agree nor disagree, Disagree, Strongly disagree". **Measure:** How pleasant patients from music intervention groups found the music **Time Frame:** Immediately after the procedure **Description:** How calming patients found the music during their cystoscopy will be measured using a 5-point Likert scale where patients rate their agreement with the statement "I found the music calming". Ratings include "Strongly agree, Agree, Neither agree nor disagree, Disagree, Strongly disagree". **Measure:** How calming patients from music intervention groups found the music **Time Frame:** Immediately after the procedure **Description:** How distracting patients found the music during their cystoscopy will be measured using a 5-point Likert scale where patients rate their agreement with the statement "The music helped distract me from the cystoscopy procedure". Ratings include "Strongly agree, Agree, Neither agree nor disagree, Disagree, Strongly disagree". **Measure:** How much patients from music intervention groups found that music helped distract them from the cystoscopy procedure **Time Frame:** Immediately after the procedure ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All outpatient men and women needing diagnostic or surveillance flexible cystoscopy. * 40 years or older. * Presenting to outpatient urology clinic. Exclusion Criteria: * Narcotics/analgesics within the past 24 hours * Stricture/anatomic urethra problems * Current UTI * Inability to complete survey or comply with experimental methods, * Refusal to participate * Rigid cystoscopy * Manipulation during cystoscopy (stent removal, fulguration tumor, etc) * Pre-existing chronic pelvic pain condition/diagnosis **Gender Based:** True **Gender Description:** This is a 1:1:1 randomization with equal group membership performed for both male and female sexes - The envelopes will be randomized by pre-assigning an order of participants to each of the three groups within each sex using a Random sequence generator. This design is to appropriately account for potential differences in cystoscopy experience for males and females, due to differences in ureter length and anatomy. **Maximum Age:** 100 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Gavin M Langille, MD **Phone:** 506-636-8818 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Ali A Sherazi, BMSc **Phone:** 506-271-1199 **Role:** CONTACT #### Locations **Location 1:** **City:** Saint John **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Gavin M Langille, MD - **Phone:** 506-636-8818 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Ali A Sherazi, BMSc - **Phone:** 506-271-1199 - **Role:** CONTACT ***Contact 3:*** - **Name:** Gavin M Langille, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Ali A Sherazi, BMSc - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Landan MacDonald, MD - **Role:** SUB_INVESTIGATOR ***Contact 6:*** - **Name:** Danielle Jenkins, MD - **Role:** SUB_INVESTIGATOR **Country:** Canada **Facility:** Saint John Regional Hospital **State:** New Brunswick **Status:** RECRUITING **Zip:** E2L 4L2 #### Overall Officials **Official 1:** **Affiliation:** Horizon Health Network, Dalhousie University Department of Urology **Name:** Gavin M Langille, MD **Role:** PRINCIPAL_INVESTIGATOR ### 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 - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06068179 **Acronym:** 3M-RGD **Brief Title:** Graves' Disease Remission Study: MycoMeth Combo **Official Title:** The Efficacy and Safety of Combining Mycophenolate Mofetil With Methimazole on Remission of Newly Diagnosis Graves' Disease (3M-RGD Trial): an Open-label, Randomized Trial #### Organization Study ID Info **ID:** XMFHIIT-2023SL059 #### Organization **Class:** OTHER **Full Name:** The First Affiliated Hospital of Xiamen University ### Status Module #### Completion Date **Date:** 2026-10-08 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-27 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-10-08 **Type:** ESTIMATED #### Start Date **Date:** 2023-10-16 **Type:** ACTUAL **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2023-10-05 **Type:** ACTUAL **Study First Submit Date:** 2023-09-28 **Study First Submit QC Date:** 2023-09-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** The First Affiliated Hospital of Xiamen 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:** A randomized study to evaluate the efficacy and safety of combining mycophenolate mofetil with methimazole in patients with newly diagnosed Graves' disease. **Detailed Description:** The remission rate of methimazole standard therapy in patients with newly diagnosed Graves' disease is only around 50%. Main reason for the low remission rate is methimazole therapy is not a drug targeting etiology of Graves' disease. The investigators hypothesize that adding mycophenolate mofetil, an immunosuppressor, to methimazole standard therapy will improve remission rate. The study will evaluate the efficacy and safety of combining mycophenolate mofetil with methimazole in patients with newly diagnosed Graves' disease. 205 eligible patients will be randomized to mycophenolate mofetil combined with methimazole therapy or methimazole standard therapy. The primary outcome is the remission rate at 12 months. ### Conditions Module **Conditions:** - Graves' Disease **Keywords:** - Newly Diagnosed Graves' Disease - Mycophenolate Mofetil - Methimazole - Remission ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Eligible patients will be randomly assigned to intervention group (Mycophenolate Mofetil combine with methimazole) or control group (methimazole standard therapy) for 12 months. ##### Masking Info **Masking:** SINGLE **Masking Description:** The study grouping will be blinded to outcomes assessor. **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 205 **Type:** ESTIMATED **Phases:** - PHASE2 - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Mycophenolate Mofetil 0.5 twice daily for 12 months added to methimazole standard therapy. **Intervention Names:** - Drug: Mycophenolate Mofetil, Oral, 250 Mg - Drug: methimazole, oral, 10mg **Label:** intervention group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Methimazole 15-30mg daily initially, then titrate to maintenance dose. Beta-blocker used when necessary. **Intervention Names:** - Drug: methimazole, oral, 10mg **Label:** control group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - intervention group **Description:** Mycophenolate Mofetil, Oral, 500Mg twice daily for 12 months, combined with methimazole standard therapy **Name:** Mycophenolate Mofetil, Oral, 250 Mg **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - control group - intervention group **Description:** Methimazole 15-30mg daily initially then titrate to maintenance dose. **Name:** methimazole, oral, 10mg **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Remission is defined as normal thyroid function, TRAb level at methimazole maintenance dose **Measure:** Remission rate **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - 1. aged 18 to 60 years. 2. Patients newly diagnosed with Graves' disease. Exclusion Criteria: * 1. Patients with Graves' disease who have undergone treatment or experienced relapse. 2. Hyperthyroidism due to other etiologies (toxic multinodular goiter, toxic thyroid adenoma, Hashimoto's thyroiditis, subacute thyroiditis, iodine-induced hyperthyroidism, etc.). 3. Individuals requiring intervention for moderate to severe thyroid eye disease at the time of enrollment. 4. Patients with hyperthyroidism requiring surgery due to concurrent thyroid cancer. 5. Those with severe liver or kidney dysfunction (ALT or AST \> 3 times the upper limit of normal reference values, blood creatinine \> 135 mol/L for males, and 110 mol/L for females). 6. Individuals with leukopenia (WBC \< 3.0×109/L). 7. Patients with severe heart failure (NYHA class III or IV). 8. Individuals with chronic or severe infections such as pulmonary tuberculosis, hepatitis B, etc. 9. Pregnant women, breastfeeding women, those planning pregnancy in the near future, or individuals who cannot comply with contraception during trial. 10. Participants in or previously involved in other clinical studies. 11. Individuals unwilling or unable to comply with follow-up or unwilling to participate. **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Fangsen Xiao, MD **Phone:** +8613859955389 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Liyin Wang, MM **Phone:** +8613950139047 **Role:** CONTACT #### Locations **Location 1:** **City:** Xiamen **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Fangsen Xiao, MD - **Phone:** +8613859955389 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Liyin Wang, MM - **Phone:** +8613950139047 - **Role:** CONTACT **Country:** China **Facility:** Xiao Fangsen **State:** Fujian **Status:** RECRUITING **Zip:** 361003 #### Overall Officials **Official 1:** **Affiliation:** The first affiliated hospital of Xiamen University Medical College **Name:** Fangsen Xiao, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** No plan to share IPD **IPD Sharing:** NO ### References Module #### References **Citation:** Davies TF, Andersen S, Latif R, Nagayama Y, Barbesino G, Brito M, Eckstein AK, Stagnaro-Green A, Kahaly GJ. Graves' disease. Nat Rev Dis Primers. 2020 Jul 2;6(1):52. doi: 10.1038/s41572-020-0184-y. **PMID:** 32616746 **Citation:** Burch HB, Cooper DS. Management of Graves Disease: A Review. JAMA. 2015 Dec 15;314(23):2544-54. doi: 10.1001/jama.2015.16535. Erratum In: JAMA. 2016 Feb 9;315(6):614. **PMID:** 26670972 **Citation:** Smith TJ, Hegedus L. Graves' Disease. N Engl J Med. 2016 Oct 20;375(16):1552-1565. doi: 10.1056/NEJMra1510030. No abstract available. **PMID:** 27797318 **Citation:** Kahaly GJ. Management of Graves Thyroidal and Extrathyroidal Disease: An Update. J Clin Endocrinol Metab. 2020 Dec 1;105(12):3704-20. doi: 10.1210/clinem/dgaa646. **PMID:** 32929476 **Citation:** Wiersinga WM. Graves' Disease: Can It Be Cured? Endocrinol Metab (Seoul). 2019 Mar;34(1):29-38. doi: 10.3803/EnM.2019.34.1.29. **PMID:** 30912336 **Citation:** Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421. doi: 10.1089/thy.2016.0229. Erratum In: Thyroid. 2017 Nov;27(11):1462. **PMID:** 27521067 **Citation:** Torlinska B, Hazlehurst JM, Nirantharakumar K, Thomas GN, Priestley JR, Finnikin SJ, Saunders P, Abrams KR, Boelaert K. wEight chanGes, caRdio-mEtabolic risks and morTality in patients with hyperthyroidism (EGRET): a protocol for a CPRD-HES linked cohort study. BMJ Open. 2021 Oct 1;11(10):e055219. doi: 10.1136/bmjopen-2021-055219. **PMID:** 34598995 **Citation:** Broen JCA, van Laar JM. Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):167-178. doi: 10.1038/s41584-020-0374-8. Epub 2020 Feb 13. **PMID:** 32055040 **Citation:** Prussick L, Plotnikova N, Gottlieb A. Mycophenolate Mofetil in Severe Atopic Dermatitis: A Review. J Drugs Dermatol. 2016 Jun 1;15(6):715-8. **PMID:** 27272078 **Citation:** Barbesino G, Salvi M, Freitag SK. Future Projections in Thyroid Eye Disease. J Clin Endocrinol Metab. 2022 Aug 8;107(Suppl_1):S47-S56. doi: 10.1210/clinem/dgac252. **PMID:** 36346684 **Citation:** Kahaly GJ, Riedl M, Konig J, Pitz S, Ponto K, Diana T, Kampmann E, Kolbe E, Eckstein A, Moeller LC, Fuhrer D, Salvi M, Curro N, Campi I, Covelli D, Leo M, Marino M, Menconi F, Marcocci C, Bartalena L, Perros P, Wiersinga WM; European Group on Graves' Orbitopathy (EUGOGO). Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet Diabetes Endocrinol. 2018 Apr;6(4):287-298. doi: 10.1016/S2213-8587(18)30020-2. Epub 2018 Jan 31. **PMID:** 29396246 **Citation:** Rajabi MT, Rafizadeh SM, Mohammadi A, Eshraghi B, Mohammadi N, Hosseini SS, Rajabi MB, Keshmirshekan MM, Shahriari M, Poursayed Lazarjani SZ, Parandin MM. Mycophenolate Mofetil (CellCept(R)) in Combination With Low Dose Prednisolone in Moderate to Severe Graves' Orbitopathy. Front Med (Lausanne). 2022 Feb 11;9:788228. doi: 10.3389/fmed.2022.788228. eCollection 2022. **PMID:** 35223896 **Citation:** Feng W, Hu Y, Zhang C, Shi H, Zhang P, Yang Y, Chen S, Cui W, Cui D. Efficacy and safety of mycophenolate mofetil in the treatment of moderate to severe Graves' orbitopathy: a meta-analysis. Bioengineered. 2022 Jun;13(6):14719-14729. doi: 10.1080/21655979.2022.2101191. **PMID:** 35959915 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005094 - Term: Exophthalmos - ID: D000009916 - Term: Orbital Diseases - ID: D000005128 - Term: Eye Diseases - ID: D000006042 - Term: Goiter - ID: D000013959 - Term: Thyroid Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000006980 - Term: Hyperthyroidism - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9214 - Name: Graves Disease - Relevance: HIGH - As Found: Graves' Disease - ID: M8237 - Name: Exophthalmos - Relevance: LOW - As Found: Unknown - ID: M12845 - Name: Orbital Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown - ID: M9147 - Name: Goiter - Relevance: LOW - As Found: Unknown - ID: M16718 - Name: Thyroid Diseases - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M10031 - Name: Hyperthyroidism - 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: D000006111 - Term: Graves Disease ### Intervention Browse Module - Ancestors - ID: D000000903 - Term: Antibiotics, Antineoplastic - ID: D000000970 - Term: Antineoplastic Agents - 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 - ID: D000013956 - Term: Antithyroid Agents - ID: D000006727 - Term: Hormone Antagonists - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M12128 - Name: Mycophenolic Acid - Relevance: HIGH - As Found: Mindfulness - ID: M3671 - Name: Adrenergic beta-Antagonists - Relevance: LOW - As Found: Unknown - ID: M11689 - Name: Methimazole - Relevance: HIGH - As Found: Autoregulation - 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 - ID: M16715 - Name: Antithyroid Agents - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000009173 - Term: Mycophenolic Acid - ID: D000008713 - Term: Methimazole ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01869179 **Acronym:** COV **Brief Title:** Community Choirs To Promote Healthy Aging; Community of Voices Chorus **Official Title:** Community Choirs To Promote Healthy Aging And Independence Of Older Adults #### Organization Study ID Info **ID:** R01AG042526 **Link:** https://reporter.nih.gov/quickSearch/R01AG042526 **Type:** NIH #### Organization **Class:** OTHER **Full Name:** University of California, San Francisco ### Status Module #### Completion Date **Date:** 2018-08-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-01-18 **Type:** ACTUAL **Last Update Submit Date:** 2020-01-13 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-12-01 **Type:** ACTUAL #### Start Date **Date:** 2013-02 **Type:** ACTUAL **Status Verified Date:** 2020-01 #### Study First Post Date **Date:** 2013-06-05 **Type:** ESTIMATED **Study First Submit Date:** 2013-01-09 **Study First Submit QC Date:** 2013-05-30 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** San Francisco Community Music Center **Class:** UNKNOWN **Name:** Department of Aging and Adults Services San Francisco #### Lead Sponsor **Class:** OTHER **Name:** University of California, San Francisco #### 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 investigators will recruit 450 older adults and will utilize 12 Administration on Aging (AoA)-supported senior centers to implement a multisite, cluster randomized (by center), wait-list clinical trial. Centers will be randomized to receive the choir program immediately (intervention group) or after a 6-month delayed intervention phase (control group). The community choirs will be led by professional music directors. The investigators will assess both primary and secondary outcomes at baseline, 6 and 12 months, with the main intervention group comparison being at 6 months. The investigators will also evaluate the start-up and ongoing program costs for senior centers, including cost/person served and determine quality adjusted life years. The hypotheses are: 1. Compared to delayed intervention controls, participation in a community choir program will be associated with improvements/maintenance on the primary outcomes of physical function (balance, walking speed, strength), depressive symptoms, and cognition (executive function and memory) at 6 months. The investigators also predict within-group improvements on these primary outcomes at 12 months. 2. Compared to delayed intervention controls, participation in a community choir program will be associated with improvements in the secondary outcomes of well-being (depressive symptoms, loneliness, resilience, social participation, health-related quality of life, shortness of breath, functional status, falls, and health services use) at 6 months. The investigators also predict within-group improvements on these secondary outcomes at 12 months. ### Conditions Module **Conditions:** - Well Being **Keywords:** - Well being - Low income - Choir singing - Spanish speaking - Community based - Seniors - 60+ aged adults - health disparities ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Cluster-randomized controlled design ##### Masking Info **Masking:** NONE **Masking Description:** Randomization assignment was not revealed to study personnel or study participants until after baseline assessments were completed for each pair of centers. **Primary Purpose:** OTHER #### Enrollment Info **Count:** 390 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive the 12 month choir program as soon as possible after study enrollment. **Intervention Names:** - Behavioral: Community of Voices choir program **Label:** Community of Voices choir program **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Waits six months, and at the end of the six months is offered the option of participating in the 12 month choir program. **Intervention Names:** - Behavioral: Community of Voices choir program - Behavioral: Wait-list control group **Label:** Wait-list control group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Community of Voices choir program - Wait-list control group **Description:** Attend weekly choir sessions for 12 months at the Senior Center. All choir sessions will include activities that focus on cognitive, psychosocial, and physical engagement components Choir sessions will last 90 minutes each with a 10 minute break. Take part in 3-4 informal choir concerts. **Name:** Community of Voices choir program **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Wait-list control group **Name:** Wait-list control group **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** We will measure several physical function outcomes. The Short Physical Performance Battery (SPPB) chair stands will be the primary outcome measure. Baseline, 6 months, 12 months. Additional motor function outcomes using the NIH Toolbox are listed below. **Measure:** Physical function **Time Frame:** up to 12 months **Description:** We will use the Trailmaking Test as a primary outcome of executive function. Baseline, 6 months, 12 months. Additional tests of executive function and memory are listed as secondary outcomes. **Measure:** Cognitive Function **Time Frame:** up to 12 months **Description:** We will use the Patient Health Questionnaire (PHQ-8) as a primary measure of depressive symptoms. Baseline, 6 months, 12 months. Additional NIH Toolbox Emotion measures are listed as secondary outcomes. **Measure:** Depressive Symptoms **Time Frame:** up to 12 months #### Secondary Outcomes **Description:** We will use the brief, self-report European Quality of Life (EQ-5D) to measure health-related quality of life. It has versions in both English and Spanish and also alternate and phone versions. It covers five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Baseline, 6 months, 12 months **Measure:** Health-Related Quality of Life **Time Frame:** up to 12 months **Description:** We will track utilization of health care services for cost analysis. The list of health care services is modified from the Chronic Disease Self-Management study and includes visits to a doctor, mental health provider (e.g., counselor, psychologist), other health providers (e.g., home health nurse, physical therapist), and emergency room and hospitalizations (and reason for stay). Participants (including those on the wait-list) will be contacted by phone every three months to complete the form about health care services used in the prior three months. Baseline, 6 months, 12 months **Measure:** Health Care Services Utilization **Time Frame:** up to 12 months **Description:** We will query frequency of falls using a single question commonly used in several large diverse studies about falls. Falls will also be assessed by phone every three months. Baseline, 6 months, 12 months **Measure:** Falls **Time Frame:** up to 12 months **Description:** We will ask three questions about shortness of breath based on Blazer and colleagues. Baseline, 6 months, 12 months **Measure:** Shortness of breath **Time Frame:** up to 12 months **Description:** We will use the NIH Toolbox Motor to assess endurance (4 Meter Walk Gait Speed Test) and balance (Standing Balance Test). Baseline, 6 months, 12 months. **Measure:** Balance and Endurance **Time Frame:** up to 12 months **Description:** As secondary cognitive outcomes, we will use the NIH Toolbox to assess executive function and attention (NIH Toolbox Flanker Inhibitory Control and Attention Test) and verbal memory (NIH Toolbox Auditory Verbal Learning Test - Rey). Baseline, 6 months, 12 months. **Measure:** Memory and Executive Function **Time Frame:** up to 12 months **Description:** We will also be using the NIH Toolbox to assess additional aspects of emotion, including psychological well-being (Positive Affect), Self-Efficacy, social relationships (Emotional Support, Friendship, Loneliness), negative affect (Fear-Affect, Sadness), Medical Outcomes Study (MOS) social support, and Apathy. Baseline, 6 months, 12 months. **Measure:** Emotion **Time Frame:** up to 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age 60 and older * Living independently * Have adequate visual and auditory acuity (with correction) to complete testing * Speak English or Spanish (including both bilingual and monolingual Spanish speakers) Exclusion Criteria: * A baseline diagnosis of dementia, determined by the screening tool or self-report of diagnosis * Have an unstable or serious medical condition that would limit participation in the weekly choir sessions or assessments, including current (but not prior) severe psychiatric disorder * Currently singing in a choir, within the last 6 months * Plans to move out of the area within 12 months **Healthy Volunteers:** True **Minimum Age:** 60 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Francisco **Country:** United States **Facility:** UCSF Institute for Health & Aging **State:** California **Zip:** 94118 #### Overall Officials **Official 1:** **Affiliation:** University of California, San Francisco **Name:** Julene K Johnson, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Johnson JK, Napoles AM, Stewart AL, Max WB, Santoyo-Olsson J, Freyre R, Allison TA, Gregorich SE. Study protocol for a cluster randomized trial of the Community of Voices choir intervention to promote the health and well-being of diverse older adults. BMC Public Health. 2015 Oct 13;15:1049. doi: 10.1186/s12889-015-2395-9. **PMID:** 26463176 **Citation:** Johnson JK, Gregorich SE, Acree M, Napoles AM, Flatt JD, Pounds D, Pabst A, Stewart AL. Recruitment and baseline characteristics of the Community of Voices choir study to promote the health and well-being of diverse older adults. Contemp Clin Trials Commun. 2017 Dec;8:106-113. doi: 10.1016/j.conctc.2017.09.006. Epub 2017 Sep 17. **PMID:** 29399643 **Citation:** Johnson JK, Stewart AL, Acree M, Napoles AM, Flatt JD, Max WB, Gregorich SE. A Community Choir Intervention to Promote Well-Being Among Diverse Older Adults: Results From the Community of Voices Trial. J Gerontol B Psychol Sci Soc Sci. 2020 Feb 14;75(3):549-559. doi: 10.1093/geronb/gby132. **PMID:** 30412233 **Citation:** Allison TA, Napoles AM, Johnson JK, Stewart AL, Rodriguez-Salazar M, Peringer J, Sherman S, Ortez-Alfaro J, Villero O, Portacolone E. Multi-cultural perspectives on group singing among diverse older adults. Geriatr Nurs. 2020 Nov-Dec;41(6):1006-1012. doi: 10.1016/j.gerinurse.2020.07.011. Epub 2020 Aug 8. **PMID:** 32778434 #### See Also Links **Label:** Community of Voices trial website, including program manual **URL:** https://cov.ucsf.edu/ ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03698279 **Acronym:** QHD04 **Brief Title:** Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age **Official Title:** Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age #### Organization Study ID Info **ID:** QHD04 #### Organization **Class:** INDUSTRY **Full Name:** Sanofi #### Secondary ID Infos **Domain:** WHO **ID:** U1111-1189-3713 **Type:** OTHER **ID:** 2018-005026-39 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2019-10-16 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-04-04 **Type:** ACTUAL **Last Update Submit Date:** 2022-03-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-10-16 **Type:** ACTUAL #### Results First Post Date **Date:** 2020-06-01 **Type:** ACTUAL **Results First Submit Date:** 2020-05-14 **Results First Submit QC Date:** 2020-05-14 #### Start Date **Date:** 2018-10-09 **Type:** ACTUAL **Status Verified Date:** 2022-03 #### Study First Post Date **Date:** 2018-10-05 **Type:** ACTUAL **Study First Submit Date:** 2018-10-04 **Study First Submit QC Date:** 2018-10-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Sanofi Pasteur, a Sanofi Company #### 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:** The objectives of this study were: * To describe the safety of each dosage of high-dose quadrivalent influenza vaccine (QIV-HD) used in the study during the 28 days following each vaccination, and serious adverse events (including adverse events of special interest throughout the study). * To describe the antibody response induced by each dosage of QIV-HD used in the study compared with unadjuvanted standard-dose quadrivalent influenza vaccine (QIV-SD) by hemagglutination inhibition (HAI) measurement method. * To describe the antibody response induced by each dosage of QIV-HD used in the study compared with unadjuvanted QIV-SD by virus seroneutralization (SN) measurement method. * To describe the antibody response induced by the highest acceptable dosage of QIV-HD compared with adjuvanted trivalent influenza vaccine (TIV) by HAI and virus SN measurement methods. **Detailed Description:** Study duration per participant was approximately 180 days for participants who received one dose of vaccine and 208 days for participants who received two doses of vaccine. ### Conditions Module **Conditions:** - Influenza ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SEQUENTIAL **Intervention Model Description:** The study was divided into 13 groups and enrolled participants in 4 stages. The study used a stepwise age de-escalation and dose ascension design for children 6 months to less than (\<) 5 years of age. ##### Masking Info **Masking:** TRIPLE **Masking Description:** Modified double-blind: the participant's parent / legally acceptable representative, the Investigator, and other study personnel remained unaware of the treatment assignments throughout the trial. An unblinded vaccine administrator administered the appropriate vaccine but was not involved in safety data collection. **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 665 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants from United States (US) (aged 6 months to 17 years) received single injection of 30 microgram (μg) QIV-HD, intramuscularly (IM) at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **Intervention Names:** - Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated) **Label:** Group 1: QIV-HD 30 μg (US: 6 months to 17 years) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **Intervention Names:** - Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated) **Label:** Group 2: QIV-HD 45 μg (US: 6 months to 17 years) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **Intervention Names:** - Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated) **Label:** Group 3: QIV-HD, 60 μg (US: 6 months to 17 years) **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **Intervention Names:** - Biological: Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated) **Label:** Group 4: Pooled QIV-SD, 15 μg (US: 6 months to 17 years) **Type:** ACTIVE_COMPARATOR #### Arm Group 5 **Description:** Participants from Canada (aged 6 to less than \[\<\] 24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **Intervention Names:** - Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated) **Label:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 months) **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **Intervention Names:** - Biological: FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated) **Label:** Group 6: Adjuvanted TIV (Canada: 6 to <24 months) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Group 1: QIV-HD 30 μg (US: 6 months to 17 years) **Description:** Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM **Name:** High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated) **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Group 2: QIV-HD 45 μg (US: 6 months to 17 years) **Description:** Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM **Name:** High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated) **Type:** BIOLOGICAL #### Intervention 3 **Arm Group Labels:** - Group 3: QIV-HD, 60 μg (US: 6 months to 17 years) - Group 5: QIV-HD, 60 μg (Canada: 6 to <24 months) **Description:** Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM **Name:** High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated) **Type:** BIOLOGICAL #### Intervention 4 **Arm Group Labels:** - Group 4: Pooled QIV-SD, 15 μg (US: 6 months to 17 years) **Description:** Pharmaceutical form: Solution for injection Route of administration: IM **Name:** Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated) **Type:** BIOLOGICAL #### Intervention 5 **Arm Group Labels:** - Group 6: Adjuvanted TIV (Canada: 6 to <24 months) **Description:** Pharmaceutical form: Solution for injection Route of administration: IM **Name:** FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated) **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB. **Measure:** Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Any Vaccination **Time Frame:** Within 30 minutes after any vaccination **Description:** An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Adverse reactions (ARs) were AEs related to vaccination. An injection site reaction was an AR at and around the injection site. Systemic AEs were all AEs that were not injection or administration site reactions. **Measure:** Number of Participants With Unsolicited Adverse Events After Any Vaccination **Time Frame:** Within 28 days after any vaccination **Description:** An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An SAE which caused death of the participant was considered as fatal SAE. Adverse events of special interest (AESIs) were defined as SAEs which included new onset of Guillain-Barré syndrome, encephalitis/myelitis (including transverse myelitis), Bell's palsy, convulsions, optic neuritis, and brachial neuritis. **Measure:** Number of Participants With Serious Adverse Events (SAEs) After Any Vaccination **Time Frame:** From Day 0 up to 6 months (i.e. 180 days) post last vaccination **Description:** Anti-influenza antibodies were measured by hemagglutination inhibition (HAI) assay for strains A/H1N1, A/H3N2, B/Victoria and B/Yamagata lineage. Seroconversion: defined as either HAI titer \<10(1/dilution) at Day 0 and post-vaccination titer greater than or equal to (\>=)40(1/dilution) at Day 28, or HAI titer \>=10(1/dilution) at Day 0 and \>=4-fold increase in HAI titer (1/dilution) at Day 28. Data for this Outcome Measure (OM) was planned to be collected and reported for dose level (QIV-HD 30μg and 45μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to complex study design and analysis of doses and age groups, QIV-SD group participants, who matched to participants in QIV-HD 30μg and 45μg dose formulations groups (who were 9 through 17 years old and shared matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable. **Measure:** Number of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Time Frame:** Day 28 post any vaccination **Description:** GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. Data for this OM was planned to be collected and reported for dose level (QIV-HD 30 μg and QIV-HD 45 μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to the complex study design and analysis of the dose formulation and age groups in the study, QIV-SD group participants, who matched to participants in the QIV-HD 30 μg and QIV-HD 45 μg dose formulations groups (who were 9 through 17 years old and shared a matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable. **Measure:** Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Time Frame:** Day 28 post any vaccination **Description:** GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. GMTRs were calculated as the ratio of GMTs post-vaccination and pre-vaccination. **Measure:** Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Time Frame:** Day 0 (pre-vaccination), Day 28 (post any vaccination) **Description:** GMT was measured for each influenza strain using HAI assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. **Measure:** Number of Participants With Neutralization Antibody Titers >= 40 (1/Dilution) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Time Frame:** Day 28 post any vaccination **Description:** GMT was measured for each influenza strain using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. **Measure:** Geometric Mean Titers of Influenza Antibodies (Measured by Seroneutralization [SN] Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Time Frame:** Day 28 post any vaccination **Description:** GMTRs of anti-influenza antibodies were measured using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage and B/Yamagata lineage. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination. **Measure:** Geometric Mean Titers Ratio of Influenza Antibodies (Measured by Seroneutralization Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Time Frame:** Day 0 (pre-vaccination), Day 28 (post any vaccination) **Description:** Neutralizing Antibody titer was measured for each influenza strain with SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage at pre-defined thresholds of \>=20, \>=40 and \>=80 (1/dilution). **Measure:** Number of Participants With Neutralization Antibody Titers Above Pre-Defined Thresholds **Time Frame:** Day 28 post any vaccination **Description:** Neutralizing Antibody titer was measured for each influenza strain with SN method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / pre-vaccination computed value. **Measure:** Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer **Time Frame:** Day 28 post any vaccination **Description:** A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions included tenderness/pain, erythema, swelling, induration and bruising. **Measure:** Number of Participants With Solicited Injection Site Reactions **Time Frame:** Within 7 days after any vaccination **Description:** A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included fever, vomiting, crying abnormal, drowsiness, appetite loss and irritability. Fever was planned to be evaluated for the whole population where as, the other events (vomiting, crying abnormal, drowsiness, appetite lost, and irritability) were planned to be evaluated only in the participants aged 6 months to \<36 months. **Measure:** Number of Participants With Solicited Systemic Reactions After Any Vaccination **Time Frame:** Within 7 days after any vaccination **Description:** A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included: headache, malaise, myalgia and shivering. **Measure:** Number of Participants With Solicited Systemic Reactions After Any Vaccination: Participants Aged >36 Months **Time Frame:** Within 7 days after any vaccination ### Eligibility Module **Eligibility Criteria:** Inclusion criteria : * Aged 6 months to 17 years on the day of inclusion. * Assent form was signed and dated by the participant (7 to 17 years of age) and informed consent form was signed and dated by the parent(s) or guardian(s) and by an independent witness, if required by local regulations. * Participant and parent/guardian were able to attend all scheduled visits and complied with all study procedures. * For participants aged \<24 months: Born at full term of pregnancy (greater than or equal to \[\>=\] 37 weeks) and/or with a birth weight \>=2.5 kilogram. Exclusion criteria: * Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche. * Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. * Receipt of any vaccine in the 30 days preceding the first study vaccination, or planned receipt of any vaccine before Visit 3 for participants receiving 1 dose of influenza vaccine or Visit 5 for participants receiving 2 doses of influenza vaccine. * For previously influenza vaccinated participants: Previous vaccination against influenza in the preceding 6 months with either the study vaccine or another vaccine. * For previously influenza unvaccinated participants: Any influenza vaccination (from birth to the day of inclusion) with either the study vaccine or another influenza vaccine. * For previously influenza unvaccinated participants: Any previous laboratory confirmed influenza infection (from birth to the day of inclusion) * Receipt of immune globulins, blood or blood-derived products in the past 3 months. * Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). * Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances. * Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on Investigator's judgement. * Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. * Current alcohol abuse or drug addiction. * Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with study conduct or completion. * Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature \>=38.0°Celsius \[\>=100.4°Fahrenheit\]). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided. * Identified as an immediate family member (i.e., spouse, natural or adopted child, grandchild, nephew, or niece) of the Investigator or employee with direct involvement in the proposed study. * Personal history of Guillain-Barré syndrome. * Any condition that in the opinion of the Investigator would pose a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine * Personal history of clinically significant development delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder. * Known seropositivity for hepatitis B or hepatitis C. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. **Healthy Volunteers:** True **Maximum Age:** 17 Years **Minimum Age:** 6 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** San Diego **Country:** United States **Facility:** Investigational Site Number 8400004 **State:** California **Zip:** 92123-1881 **Location 2:** **City:** Miami **Country:** United States **Facility:** Investigational Site Number 8400001 **State:** Florida **Zip:** 33186 **Location 3:** **City:** Atlanta **Country:** United States **Facility:** Investigational Site Number 8400002 **State:** Georgia **Zip:** 30322 **Location 4:** **City:** El Dorado **Country:** United States **Facility:** Investigational Site Number 8400013 **State:** Kansas **Zip:** 67042 **Location 5:** **City:** Newton **Country:** United States **Facility:** Investigational Site Number 8400015 **State:** Kansas **Zip:** 67114 **Location 6:** **City:** Wichita **Country:** United States **Facility:** Investigational Site Number 8400009 **State:** Kansas **Zip:** 67207 **Location 7:** **City:** Metairie **Country:** United States **Facility:** Investigational Site Number 8400007 **State:** Louisiana **Zip:** 70006 **Location 8:** **City:** Las Vegas **Country:** United States **Facility:** Investigational Site Number 8400010 **State:** Nevada **Zip:** 89104 **Location 9:** **City:** Warwick **Country:** United States **Facility:** Investigational Site Number 8400011 **State:** Rhode Island **Zip:** 02886 **Location 10:** **City:** Salt Lake City **Country:** United States **Facility:** Investigational Site Number 8400003 **State:** Utah **Zip:** 84107 **Location 11:** **City:** Salt Lake City **Country:** United States **Facility:** Investigational Site Number 8400012 **State:** Utah **Zip:** 84109 **Location 12:** **City:** Salt Lake City **Country:** United States **Facility:** Investigational Site Number 8400005 **State:** Utah **Zip:** 84121 **Location 13:** **City:** West Jordan **Country:** United States **Facility:** Investigational Site Number 8400014 **State:** Utah **Zip:** 84088-8865 **Location 14:** **City:** Montreal **Country:** Canada **Facility:** Investigational Site Number 1241003 **Zip:** H3T 1C5 **Location 15:** **City:** Pierrefonds **Country:** Canada **Facility:** Investigational Site Number 1241002 **Zip:** H9H 4Y6 **Location 16:** **City:** Quebec **Country:** Canada **Facility:** Investigational Site Number 1241001 **Zip:** G1E 7G9 #### Overall Officials **Official 1:** **Affiliation:** Sanofi Pasteur, a Sanofi Company **Name:** Clinical Sciences & Operations **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org **IPD Sharing:** YES ### References Module #### References **Citation:** Chang LJ, Anderson EJ, Jeanfreau R, He Y, Hicks B, Shrestha A, Pandey A, Landolfi V, DeBruijn I; QHD04 Study Group. Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through <18 years of age: A randomized controlled phase II dose-finding trial. Vaccine. 2021 Mar 12;39(11):1572-1582. doi: 10.1016/j.vaccine.2021.02.014. Epub 2021 Feb 18. **PMID:** 33610374 ## Document Section ### Large Document Module #### Large Docs - Date: 2019-02-25 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 2040806 - Type Abbrev: Prot - Upload Date: 2020-05-14T12:01 - Date: 2019-07-04 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 1174192 - Type Abbrev: SAP - Upload Date: 2020-05-14T12:01 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000009976 - Term: Orthomyxoviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus 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: M10295 - Name: Influenza, Human - Relevance: HIGH - As Found: Influenza - 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: M12902 - Name: Orthomyxoviridae 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: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007251 - Term: Influenza, Human ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: HIGH - As Found: Other - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014612 - Term: Vaccines ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** An SR was an AE that was prelisted (i.e., solicited) in the CRB and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the CRB in terms of diagnosis and/or onset window post-vaccination. Analysis was performed on SafAS population. #### Event Groups **Group ID:** EG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) **Deaths Num At Risk:** 122 **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** EG000 **Other Num Affected:** 101 **Other Num at Risk:** 122 **Serious Number At Risk:** 122 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) **Group ID:** EG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) **Deaths Num At Risk:** 121 **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** EG001 **Other Num Affected:** 100 **Other Num at Risk:** 121 **Serious Number At Risk:** 121 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) **Group ID:** EG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) **Deaths Num At Risk:** 158 **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** EG002 **Other Num Affected:** 118 **Other Num at Risk:** 158 **Serious Number Affected:** 2 **Serious Number At Risk:** 158 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) **Group ID:** EG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) **Deaths Num At Risk:** 234 **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** EG003 **Other Num Affected:** 165 **Other Num at Risk:** 234 **Serious Number At Risk:** 234 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) **Group ID:** EG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) **Deaths Num At Risk:** 13 **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** EG004 **Other Num Affected:** 13 **Other Num at Risk:** 13 **Serious Number At Risk:** 13 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) **Group ID:** EG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) **Deaths Num At Risk:** 13 **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** EG005 **Other Num Affected:** 13 **Other Num at Risk:** 13 **Serious Number Affected:** 1 **Serious Number At Risk:** 13 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) **Frequency Threshold:** 5 #### Other Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Ear Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Abdominal Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Oral Mucosal Eruption **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Teething **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Chills **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Crying **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Influenza Like Illness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Injection Site Bruising **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Injection Site Erythema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Injection Site Induration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Injection Site Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Injection Site Swelling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Injection Site Warmth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Malaise **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Bronchiolitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Conjunctivitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Ear Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Otitis Media **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Pharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Upper Respiratory Tract Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 **Term:** Tongue Injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA-22.0 **Term:** Decreased Appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Aphonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Somnolence **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Irritability **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Sleep Terror **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Nasal Congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Rhinorrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Dermatitis Diaper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Erythema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Petechiae **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA-22.0 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA-22.0 #### Serious Events **Term:** Ear Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 121 **Group ID:** EG002 **Num At Risk:** 158 **Group ID:** EG003 **Num At Risk:** 234 **Group ID:** EG004 **Num At Risk:** 13 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Term:** Respiratory Syncytial Virus Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA-22.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 121 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 158 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 234 **Group ID:** EG004 **Num At Risk:** 13 **Group ID:** EG005 **Num At Risk:** 13 **Term:** Febrile Convulsion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA-22.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 122 **Group ID:** EG001 **Num At Risk:** 121 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 158 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 234 **Group ID:** EG004 **Num At Risk:** 13 **Group ID:** EG005 **Num At Risk:** 13 **Time Frame:** AEs were collected from Day 0 (post-vaccination) up to 28 days after last vaccination. Solicited Reaction (SR) data were collected up to Day 7 after any vaccination. SAE data were collected throughout the study (up to 180 days after last vaccination). ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 124 **Group ID:** BG001 **Value:** 122 **Group ID:** BG002 **Value:** 159 **Group ID:** BG003 **Value:** 234 **Group ID:** BG004 **Value:** 13 **Group ID:** BG005 **Value:** 13 **Group ID:** BG006 **Value:** 665 **Units:** Participants ### Group **ID:** BG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. ### Group **ID:** BG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. ### Group **ID:** BG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. ### Group **ID:** BG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. ### Group **ID:** BG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. ### Group **ID:** BG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. ### Group **ID:** BG006 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 3.91 **Value:** 5.8 #### Measurement **Group ID:** BG001 **Spread:** 4.30 **Value:** 6.1 #### Measurement **Group ID:** BG002 **Spread:** 4.22 **Value:** 5.2 #### Measurement **Group ID:** BG003 **Spread:** 4.02 **Value:** 5.1 #### Measurement **Group ID:** BG004 **Spread:** 0.19 **Value:** 0.8 #### Measurement **Group ID:** BG005 **Spread:** 0.28 **Value:** 1.0 #### Measurement **Group ID:** BG006 **Spread:** 4.13 **Value:** 5.3 **Class Title:** ### 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:** 13 #### Measurement **Group ID:** BG005 **Value:** 13 #### Measurement **Group ID:** BG006 **Value:** 26 **Class Title:** 6 - < 24 months #### Measurement **Group ID:** BG000 **Value:** 29 #### Measurement **Group ID:** BG001 **Value:** 30 #### Measurement **Group ID:** BG002 **Value:** 54 #### Measurement **Group ID:** BG003 **Value:** 75 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 188 **Class Title:** 6 - < 36 months #### Measurement **Group ID:** BG000 **Value:** 34 #### Measurement **Group ID:** BG001 **Value:** 30 #### Measurement **Group ID:** BG002 **Value:** 44 #### Measurement **Group ID:** BG003 **Value:** 68 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 176 **Class Title:** 36 months - < 5 years #### Measurement **Group ID:** BG000 **Value:** 32 #### Measurement **Group ID:** BG001 **Value:** 32 #### Measurement **Group ID:** BG002 **Value:** 31 #### Measurement **Group ID:** BG003 **Value:** 49 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 144 **Class Title:** 5 - 8 years #### Measurement **Group ID:** BG000 **Value:** 29 #### Measurement **Group ID:** BG001 **Value:** 30 #### Measurement **Group ID:** BG002 **Value:** 30 #### Measurement **Group ID:** BG003 **Value:** 42 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 131 **Class Title:** 9 - 17 years ### Measure #### Measurement **Group ID:** BG000 **Value:** 51 #### Measurement **Group ID:** BG001 **Value:** 61 #### Measurement **Group ID:** BG002 **Value:** 82 #### Measurement **Group ID:** BG003 **Value:** 114 #### Measurement **Group ID:** BG004 **Value:** 4 #### Measurement **Group ID:** BG005 **Value:** 6 #### Measurement **Group ID:** BG006 **Value:** 318 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 73 #### Measurement **Group ID:** BG001 **Value:** 61 #### Measurement **Group ID:** BG002 **Value:** 77 #### Measurement **Group ID:** BG003 **Value:** 120 #### Measurement **Group ID:** BG004 **Value:** 9 #### Measurement **Group ID:** BG005 **Value:** 7 #### Measurement **Group ID:** BG006 **Value:** 347 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 2 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 4 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 3 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 6 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 5 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 1 #### Measurement **Group ID:** BG006 **Value:** 11 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 28 #### Measurement **Group ID:** BG002 **Value:** 40 #### Measurement **Group ID:** BG003 **Value:** 58 #### Measurement **Group ID:** BG004 **Value:** 2 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 150 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 92 #### Measurement **Group ID:** BG001 **Value:** 81 #### Measurement **Group ID:** BG002 **Value:** 108 #### Measurement **Group ID:** BG003 **Value:** 157 #### Measurement **Group ID:** BG004 **Value:** 9 #### Measurement **Group ID:** BG005 **Value:** 11 #### Measurement **Group ID:** BG006 **Value:** 458 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 8 #### Measurement **Group ID:** BG003 **Value:** 7 #### Measurement **Group ID:** BG004 **Value:** 2 #### Measurement **Group ID:** BG005 **Value:** 1 #### Measurement **Group ID:** BG006 **Value:** 25 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 2 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 11 **Category Title:** Unknown or Not Reported **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:** 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:** Race (NIH/OMB) **Unit of Measure:** Participants **Population Description:** Analysis was performed on the randomized participants. ## Results Section - More Information Module ### Certain Agreement **Other Details:** The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable participant matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Sanofi Pasteur **Phone:** 800-633-1610 **Phone Extension:** 1# **Title:** Trial Transparency Team ## 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 ## 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:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 46 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 46 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 53 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **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:** 3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 46 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 52 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **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 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 107 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 98 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 110 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 141 - **Group ID:** OG003 - **Value:** 39 - **Group ID:** OG004 - **Value:** 41 - **Group ID:** OG005 - **Value:** 148 - **Group ID:** OG006 - **Value:** 11 - **Group ID:** OG007 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 63 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 102 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 109 - **Group ID:** OG001 - **Value:** 111 - **Group ID:** OG002 - **Value:** 140 - **Group ID:** OG003 - **Value:** 38 - **Group ID:** OG004 - **Value:** 41 - **Group ID:** OG005 - **Value:** 146 - **Group ID:** OG006 - **Value:** 11 - **Group ID:** OG007 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 117 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 110 - **Group ID:** OG001 - **Value:** 111 - **Group ID:** OG002 - **Value:** 141 - **Group ID:** OG003 - **Value:** 39 - **Group ID:** OG004 - **Value:** 41 - **Group ID:** OG005 - **Value:** 148 - **Group ID:** OG006 - **Value:** 11 - **Group ID:** OG007 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 85 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 120 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 117 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 110 - **Group ID:** OG001 - **Value:** 109 - **Group ID:** OG002 - **Value:** 141 - **Group ID:** OG003 - **Value:** 38 - **Group ID:** OG004 - **Value:** 41 - **Group ID:** OG005 - **Value:** 147 - **Group ID:** OG006 - **Value:** 11 - **Group ID:** OG007 - **Value:** 12 **Units:** Participants #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 525 - **Spread:** - **Upper Limit:** 863 - **Value:** 673 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 524 - **Spread:** - **Upper Limit:** 873 - **Value:** 676 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 674 - **Spread:** - **Upper Limit:** 1033 - **Value:** 834 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 419 - **Spread:** - **Upper Limit:** 1161 - **Value:** 698 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 480 - **Spread:** - **Upper Limit:** 1303 - **Value:** 791 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 461 - **Spread:** - **Upper Limit:** 830 - **Value:** 618 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 27.0 - **Spread:** - **Upper Limit:** 132 - **Value:** 59.7 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 261 - **Spread:** - **Upper Limit:** 1398 - **Value:** 604 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 116 - **Group ID:** OG001 - **Value:** 114 - **Group ID:** OG002 - **Value:** 145 - **Group ID:** OG003 - **Value:** 40 - **Group ID:** OG004 - **Value:** 41 - **Group ID:** OG005 - **Value:** 151 - **Group ID:** OG006 - **Value:** 13 - **Group ID:** OG007 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 399 - **Spread:** - **Upper Limit:** 671 - **Value:** 518 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 600 - **Spread:** - **Upper Limit:** 1017 - **Value:** 781 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 604 - **Spread:** - **Upper Limit:** 982 - **Value:** 770 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 184 - **Spread:** - **Upper Limit:** 538 - **Value:** 314 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 264 - **Spread:** - **Upper Limit:** 738 - **Value:** 441 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 239 - **Spread:** - **Upper Limit:** 395 - **Value:** 307 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 33.0 - **Spread:** - **Upper Limit:** 133 - **Value:** 66.4 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 386 - **Spread:** - **Upper Limit:** 946 - **Value:** 604 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 116 - **Group ID:** OG001 - **Value:** 113 - **Group ID:** OG002 - **Value:** 144 - **Group ID:** OG003 - **Value:** 39 - **Group ID:** OG004 - **Value:** 41 - **Group ID:** OG005 - **Value:** 151 - **Group ID:** OG006 - **Value:** 13 - **Group ID:** OG007 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 296 - **Spread:** - **Upper Limit:** 483 - **Value:** 378 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 334 - **Spread:** - **Upper Limit:** 560 - **Value:** 432 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 400 - **Spread:** - **Upper Limit:** 612 - **Value:** 494 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 194 - **Spread:** - **Upper Limit:** 452 - **Value:** 296 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 302 - **Spread:** - **Upper Limit:** 726 - **Value:** 468 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 246 - **Spread:** - **Upper Limit:** 390 - **Value:** 310 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 26.2 - **Spread:** - **Upper Limit:** 122 - **Value:** 56.6 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 767 - **Spread:** - **Upper Limit:** 2016 - **Value:** 1244 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 116 - **Group ID:** OG001 - **Value:** 113 - **Group ID:** OG002 - **Value:** 145 - **Group ID:** OG003 - **Value:** 40 - **Group ID:** OG004 - **Value:** 41 - **Group ID:** OG005 - **Value:** 151 - **Group ID:** OG006 - **Value:** 13 - **Group ID:** OG007 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 582 - **Spread:** - **Upper Limit:** 899 - **Value:** 723 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 556 - **Spread:** - **Upper Limit:** 932 - **Value:** 720 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 722 - **Spread:** - **Upper Limit:** 1066 - **Value:** 877 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 474 - **Spread:** - **Upper Limit:** 1050 - **Value:** 706 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 501 - **Spread:** - **Upper Limit:** 1054 - **Value:** 727 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 466 - **Spread:** - **Upper Limit:** 721 - **Value:** 580 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 38.9 - **Spread:** - **Upper Limit:** 148 - **Value:** 75.8 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 12.3 - **Spread:** - **Upper Limit:** 38.6 - **Value:** 21.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 116 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 144 - **Group ID:** OG003 - **Value:** 39 - **Group ID:** OG004 - **Value:** 41 - **Group ID:** OG005 - **Value:** 151 - **Group ID:** OG006 - **Value:** 13 - **Group ID:** OG007 - **Value:** 12 **Units:** Participants #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.39 - **Spread:** - **Upper Limit:** 11.4 - **Value:** 8.55 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.31 - **Spread:** - **Upper Limit:** 13.7 - **Value:** 10.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 12.1 - **Spread:** - **Upper Limit:** 22.0 - **Value:** 16.3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 8.07 - **Spread:** - **Upper Limit:** 12.8 - **Value:** 10.1 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 0.878 - **Spread:** - **Upper Limit:** 2.28 - **Value:** 1.41 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 2.72 - **Spread:** - **Upper Limit:** 8.32 - **Value:** 4.76 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 110 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 141 - **Group ID:** OG003 - **Value:** 217 - **Group ID:** OG004 - **Value:** 11 - **Group ID:** OG005 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.95 - **Spread:** - **Upper Limit:** 8.34 - **Value:** 6.42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.15 - **Spread:** - **Upper Limit:** 12.2 - **Value:** 9.35 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 8.09 - **Spread:** - **Upper Limit:** 13.0 - **Value:** 10.3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 3.90 - **Spread:** - **Upper Limit:** 5.45 - **Value:** 4.61 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 1.00 - **Spread:** - **Upper Limit:** 2.00 - **Value:** 1.41 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 8.89 - **Spread:** - **Upper Limit:** 27.2 - **Value:** 15.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 109 - **Group ID:** OG001 - **Value:** 111 - **Group ID:** OG002 - **Value:** 140 - **Group ID:** OG003 - **Value:** 214 - **Group ID:** OG004 - **Value:** 11 - **Group ID:** OG005 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8.31 - **Spread:** - **Upper Limit:** 13.7 - **Value:** 10.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 9.30 - **Spread:** - **Upper Limit:** 14.7 - **Value:** 11.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 13.2 - **Spread:** - **Upper Limit:** 21.0 - **Value:** 16.7 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 9.24 - **Spread:** - **Upper Limit:** 13.2 - **Value:** 11.0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 0.949 - **Spread:** - **Upper Limit:** 1.98 - **Value:** 1.37 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 6.28 - **Spread:** - **Upper Limit:** 19.2 - **Value:** 11.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 110 - **Group ID:** OG001 - **Value:** 111 - **Group ID:** OG002 - **Value:** 141 - **Group ID:** OG003 - **Value:** 217 - **Group ID:** OG004 - **Value:** 11 - **Group ID:** OG005 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7.10 - **Spread:** - **Upper Limit:** 12.1 - **Value:** 9.28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 8.83 - **Spread:** - **Upper Limit:** 14.7 - **Value:** 11.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 13.9 - **Spread:** - **Upper Limit:** 23.6 - **Value:** 18.1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 8.15 - **Spread:** - **Upper Limit:** 11.7 - **Value:** 9.77 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 1.07 - **Spread:** - **Upper Limit:** 2.73 - **Value:** 1.71 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 0.785 - **Spread:** - **Upper Limit:** 1.13 - **Value:** 0.944 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 110 - **Group ID:** OG001 - **Value:** 109 - **Group ID:** OG002 - **Value:** 141 - **Group ID:** OG003 - **Value:** 215 - **Group ID:** OG004 - **Value:** 11 - **Group ID:** OG005 - **Value:** 12 **Units:** Participants #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 113 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 110 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 142 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 198 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 116 - **Group ID:** OG001 - **Value:** 114 - **Group ID:** OG002 - **Value:** 145 - **Group ID:** OG003 - **Value:** 221 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 110 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 139 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 198 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 116 - **Group ID:** OG001 - **Value:** 113 - **Group ID:** OG002 - **Value:** 144 - **Group ID:** OG003 - **Value:** 220 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 112 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 108 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 140 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 202 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 116 - **Group ID:** OG001 - **Value:** 113 - **Group ID:** OG002 - **Value:** 145 - **Group ID:** OG003 - **Value:** 221 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 115 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 109 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 142 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 215 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 116 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 144 - **Group ID:** OG003 - **Value:** 220 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 12 **Units:** Participants #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4959 - **Spread:** - **Upper Limit:** 8754 - **Value:** 6589 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4672 - **Spread:** - **Upper Limit:** 8264 - **Value:** 6213 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 5514 - **Spread:** - **Upper Limit:** 9001 - **Value:** 7045 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 3676 - **Spread:** - **Upper Limit:** 6659 - **Value:** 4948 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 14.8 - **Spread:** - **Upper Limit:** 76.9 - **Value:** 33.8 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 32.0 - **Spread:** - **Upper Limit:** 1708 - **Value:** 234 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 112 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 147 - **Group ID:** OG003 - **Value:** 216 - **Group ID:** OG004 - **Value:** 12 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 515 - **Spread:** - **Upper Limit:** 798 - **Value:** 641 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 718 - **Spread:** - **Upper Limit:** 1181 - **Value:** 921 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 717 - **Spread:** - **Upper Limit:** 1091 - **Value:** 884 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 347 - **Spread:** - **Upper Limit:** 487 - **Value:** 411 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 35.3 - **Spread:** - **Upper Limit:** 83.9 - **Value:** 54.4 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 119 - **Spread:** - **Upper Limit:** 298 - **Value:** 188 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 113 - **Group ID:** OG001 - **Value:** 111 - **Group ID:** OG002 - **Value:** 142 - **Group ID:** OG003 - **Value:** 215 - **Group ID:** OG004 - **Value:** 11 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 375 - **Spread:** - **Upper Limit:** 667 - **Value:** 500 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 444 - **Spread:** - **Upper Limit:** 825 - **Value:** 605 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 484 - **Spread:** - **Upper Limit:** 815 - **Value:** 628 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 302 - **Spread:** - **Upper Limit:** 472 - **Value:** 378 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 4.54 - **Spread:** - **Upper Limit:** 8.07 - **Value:** 6.05 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 39.5 - **Spread:** - **Upper Limit:** 84.9 - **Value:** 57.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 113 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 146 - **Group ID:** OG003 - **Value:** 216 - **Group ID:** OG004 - **Value:** 12 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 893 - **Spread:** - **Upper Limit:** 1474 - **Value:** 1147 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 865 - **Spread:** - **Upper Limit:** 1552 - **Value:** 1159 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 1015 - **Spread:** - **Upper Limit:** 1549 - **Value:** 1254 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 698 - **Spread:** - **Upper Limit:** 1026 - **Value:** 846 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 11.1 - **Spread:** - **Upper Limit:** 27.8 - **Value:** 17.6 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 9.86 - **Spread:** - **Upper Limit:** 30.6 - **Value:** 17.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 112 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 146 - **Group ID:** OG003 - **Value:** 214 - **Group ID:** OG004 - **Value:** 12 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7.67 - **Spread:** - **Upper Limit:** 16.7 - **Value:** 11.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 12.1 - **Spread:** - **Upper Limit:** 29.4 - **Value:** 18.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 19.6 - **Spread:** - **Upper Limit:** 43.2 - **Value:** 29.1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 11.0 - **Spread:** - **Upper Limit:** 19.0 - **Value:** 14.5 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 0.663 - **Spread:** - **Upper Limit:** 8.53 - **Value:** 2.38 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 3.00 - **Spread:** - **Upper Limit:** 16.9 - **Value:** 7.12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 103 - **Group ID:** OG001 - **Value:** 105 - **Group ID:** OG002 - **Value:** 138 - **Group ID:** OG003 - **Value:** 206 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.98 - **Spread:** - **Upper Limit:** 4.34 - **Value:** 3.60 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4.11 - **Spread:** - **Upper Limit:** 6.59 - **Value:** 5.20 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 4.58 - **Spread:** - **Upper Limit:** 6.70 - **Value:** 5.54 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 2.34 - **Spread:** - **Upper Limit:** 3.04 - **Value:** 2.66 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 0.629 - **Spread:** - **Upper Limit:** 1.72 - **Value:** 1.04 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 1.65 - **Spread:** - **Upper Limit:** 4.78 - **Value:** 2.81 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 101 - **Group ID:** OG001 - **Value:** 101 - **Group ID:** OG002 - **Value:** 134 - **Group ID:** OG003 - **Value:** 206 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 9.51 - **Spread:** - **Upper Limit:** 16.2 - **Value:** 12.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 11.9 - **Spread:** - **Upper Limit:** 20.0 - **Value:** 15.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 15.1 - **Spread:** - **Upper Limit:** 26.3 - **Value:** 19.9 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 10.4 - **Spread:** - **Upper Limit:** 15.4 - **Value:** 12.7 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 0.612 - **Spread:** - **Upper Limit:** 1.74 - **Value:** 1.03 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 6.73 - **Spread:** - **Upper Limit:** 16.3 - **Value:** 10.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 102 - **Group ID:** OG001 - **Value:** 105 - **Group ID:** OG002 - **Value:** 137 - **Group ID:** OG003 - **Value:** 205 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7.50 - **Spread:** - **Upper Limit:** 12.7 - **Value:** 9.75 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 9.06 - **Spread:** - **Upper Limit:** 14.7 - **Value:** 11.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 11.1 - **Spread:** - **Upper Limit:** 17.8 - **Value:** 14.1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 7.18 - **Spread:** - **Upper Limit:** 10.0 - **Value:** 8.49 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 0.604 - **Spread:** - **Upper Limit:** 2.24 - **Value:** 1.16 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 0.760 - **Spread:** - **Upper Limit:** 1.61 - **Value:** 1.10 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 101 - **Group ID:** OG001 - **Value:** 103 - **Group ID:** OG002 - **Value:** 137 - **Group ID:** OG003 - **Value:** 204 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 112 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 112 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 147 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 208 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 112 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 147 - **Group ID:** OG003 - **Value:** 216 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 112 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 112 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 147 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 202 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 112 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 147 - **Group ID:** OG003 - **Value:** 216 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 146 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 201 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 112 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 147 - **Group ID:** OG003 - **Value:** 216 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 113 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 142 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 214 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 113 - **Group ID:** OG001 - **Value:** 111 - **Group ID:** OG002 - **Value:** 142 - **Group ID:** OG003 - **Value:** 215 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 141 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 208 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 113 - **Group ID:** OG001 - **Value:** 111 - **Group ID:** OG002 - **Value:** 142 - **Group ID:** OG003 - **Value:** 215 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 107 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 107 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 138 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 190 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 113 - **Group ID:** OG001 - **Value:** 111 - **Group ID:** OG002 - **Value:** 142 - **Group ID:** OG003 - **Value:** 215 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 110 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 108 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 143 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 201 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 113 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 146 - **Group ID:** OG003 - **Value:** 216 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 108 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 104 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 136 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 195 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 113 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 146 - **Group ID:** OG003 - **Value:** 216 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 99 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 99 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 128 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 181 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 113 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 146 - **Group ID:** OG003 - **Value:** 216 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 112 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 146 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 213 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 112 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 146 - **Group ID:** OG003 - **Value:** 214 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 108 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 145 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 208 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 112 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 146 - **Group ID:** OG003 - **Value:** 214 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 110 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 103 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 140 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 201 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 112 - **Group ID:** OG001 - **Value:** 112 - **Group ID:** OG002 - **Value:** 146 - **Group ID:** OG003 - **Value:** 214 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 83 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 118 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 168 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 103 - **Group ID:** OG001 - **Value:** 105 - **Group ID:** OG002 - **Value:** 138 - **Group ID:** OG003 - **Value:** 206 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 65 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 70 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 104 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 141 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 103 - **Group ID:** OG001 - **Value:** 105 - **Group ID:** OG002 - **Value:** 138 - **Group ID:** OG003 - **Value:** 206 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 77 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 110 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 101 - **Group ID:** OG001 - **Value:** 101 - **Group ID:** OG002 - **Value:** 134 - **Group ID:** OG003 - **Value:** 206 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 101 - **Group ID:** OG001 - **Value:** 101 - **Group ID:** OG002 - **Value:** 134 - **Group ID:** OG003 - **Value:** 206 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 95 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 99 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 131 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 185 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 102 - **Group ID:** OG001 - **Value:** 105 - **Group ID:** OG002 - **Value:** 137 - **Group ID:** OG003 - **Value:** 205 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 88 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 113 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 158 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 102 - **Group ID:** OG001 - **Value:** 105 - **Group ID:** OG002 - **Value:** 137 - **Group ID:** OG003 - **Value:** 205 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 95 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 127 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 187 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 101 - **Group ID:** OG001 - **Value:** 103 - **Group ID:** OG002 - **Value:** 137 - **Group ID:** OG003 - **Value:** 204 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 81 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 109 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 142 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 101 - **Group ID:** OG001 - **Value:** 103 - **Group ID:** OG002 - **Value:** 137 - **Group ID:** OG003 - **Value:** 204 - **Group ID:** OG004 - **Value:** 10 - **Group ID:** OG005 - **Value:** 11 **Units:** Participants #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 81 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 100 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 116 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 40 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 48 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 34 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 122 - **Group ID:** OG001 - **Value:** 120 - **Group ID:** OG002 - **Value:** 158 - **Group ID:** OG003 - **Value:** 231 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 29 - **Group ID:** OG001 - **Value:** 30 - **Group ID:** OG002 - **Value:** 54 - **Group ID:** OG003 - **Value:** 74 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 29 - **Group ID:** OG001 - **Value:** 30 - **Group ID:** OG002 - **Value:** 54 - **Group ID:** OG003 - **Value:** 74 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 29 - **Group ID:** OG001 - **Value:** 30 - **Group ID:** OG002 - **Value:** 54 - **Group ID:** OG003 - **Value:** 74 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 29 - **Group ID:** OG001 - **Value:** 30 - **Group ID:** OG002 - **Value:** 54 - **Group ID:** OG003 - **Value:** 74 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 29 - **Group ID:** OG001 - **Value:** 30 - **Group ID:** OG002 - **Value:** 54 - **Group ID:** OG003 - **Value:** 74 - **Group ID:** OG004 - **Value:** 13 - **Group ID:** OG005 - **Value:** 13 **Units:** Participants #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 42 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on SafAS population which included participants who had received at least one dose of the study vaccines. **Reporting Status:** POSTED **Time Frame:** Within 30 minutes after any vaccination **Title:** Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Any Vaccination **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 2 **Description:** An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Adverse reactions (ARs) were AEs related to vaccination. An injection site reaction was an AR at and around the injection site. Systemic AEs were all AEs that were not injection or administration site reactions. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on the SafAS population. **Reporting Status:** POSTED **Time Frame:** Within 28 days after any vaccination **Title:** Number of Participants With Unsolicited Adverse Events After Any Vaccination **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 3 **Description:** An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An SAE which caused death of the participant was considered as fatal SAE. Adverse events of special interest (AESIs) were defined as SAEs which included new onset of Guillain-Barré syndrome, encephalitis/myelitis (including transverse myelitis), Bell's palsy, convulsions, optic neuritis, and brachial neuritis. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on the SafAS population. **Reporting Status:** POSTED **Time Frame:** From Day 0 up to 6 months (i.e. 180 days) post last vaccination **Title:** Number of Participants With Serious Adverse Events (SAEs) After Any Vaccination **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 4 **Description:** Anti-influenza antibodies were measured by hemagglutination inhibition (HAI) assay for strains A/H1N1, A/H3N2, B/Victoria and B/Yamagata lineage. Seroconversion: defined as either HAI titer \<10(1/dilution) at Day 0 and post-vaccination titer greater than or equal to (\>=)40(1/dilution) at Day 28, or HAI titer \>=10(1/dilution) at Day 0 and \>=4-fold increase in HAI titer (1/dilution) at Day 28. Data for this Outcome Measure (OM) was planned to be collected and reported for dose level (QIV-HD 30μg and 45μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to complex study design and analysis of doses and age groups, QIV-SD group participants, who matched to participants in QIV-HD 30μg and 45μg dose formulations groups (who were 9 through 17 years old and shared matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on immunogenicity analysis set (IAS) population which included randomized participants who received 1 dose or 2 doses of study vaccine and had a post-vaccination blood sample. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Day 28 post any vaccination **Title:** Number of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 30 μg. **ID:** OG003 **Title:** Group 4a: QIV-SD, 15 μg, (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 45 μg. **ID:** OG004 **Title:** Group 4b: QIV-SD, 15 μg, (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 60 μg. **ID:** OG005 **Title:** Group 4c: QIV-SD, 15 μg, (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG006 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG007 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 5 **Description:** GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. Data for this OM was planned to be collected and reported for dose level (QIV-HD 30 μg and QIV-HD 45 μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to the complex study design and analysis of the dose formulation and age groups in the study, QIV-SD group participants, who matched to participants in the QIV-HD 30 μg and QIV-HD 45 μg dose formulations groups (who were 9 through 17 years old and shared a matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** GEOMETRIC_MEAN **Population Description:** Analysis was performed on IAS population. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Day 28 post any vaccination **Title:** Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Type:** PRIMARY **Unit of Measure:** titers (1/dilution) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 30 μg. **ID:** OG003 **Title:** Group 4a: QIV-SD, 15 μg, (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 45 μg. **ID:** OG004 **Title:** Group 4b: QIV-SD, 15 μg, (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 60 μg. **ID:** OG005 **Title:** Group 4c: QIV-SD, 15 μg, (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG006 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG007 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 6 **Description:** GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. GMTRs were calculated as the ratio of GMTs post-vaccination and pre-vaccination. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** GEOMETRIC_MEAN **Population Description:** Analysis was performed on IAS population. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Day 0 (pre-vaccination), Day 28 (post any vaccination) **Title:** Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Type:** PRIMARY **Unit of Measure:** ratio ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 7 **Description:** GMT was measured for each influenza strain using HAI assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on the IAS population. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Day 28 post any vaccination **Title:** Number of Participants With Neutralization Antibody Titers >= 40 (1/Dilution) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 8 **Description:** GMT was measured for each influenza strain using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** GEOMETRIC_MEAN **Population Description:** Analysis was performed on the IAS population. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Day 28 post any vaccination **Title:** Geometric Mean Titers of Influenza Antibodies (Measured by Seroneutralization [SN] Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Type:** PRIMARY **Unit of Measure:** titers (1/dilution) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 9 **Description:** GMTRs of anti-influenza antibodies were measured using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage and B/Yamagata lineage. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** GEOMETRIC_MEAN **Population Description:** Analysis was performed on IAS population. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Day 0 (pre-vaccination), Day 28 (post any vaccination) **Title:** Geometric Mean Titers Ratio of Influenza Antibodies (Measured by Seroneutralization Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine **Type:** PRIMARY **Unit of Measure:** ratio ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 10 **Description:** Neutralizing Antibody titer was measured for each influenza strain with SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage at pre-defined thresholds of \>=20, \>=40 and \>=80 (1/dilution). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on the IAS population. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Day 28 post any vaccination **Title:** Number of Participants With Neutralization Antibody Titers Above Pre-Defined Thresholds **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 11 **Description:** Neutralizing Antibody titer was measured for each influenza strain with SN method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / pre-vaccination computed value. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on the IAS population. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Day 28 post any vaccination **Title:** Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 12 **Description:** A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions included tenderness/pain, erythema, swelling, induration and bruising. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on the SafAS population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Within 7 days after any vaccination **Title:** Number of Participants With Solicited Injection Site Reactions **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 13 **Description:** A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included fever, vomiting, crying abnormal, drowsiness, appetite loss and irritability. Fever was planned to be evaluated for the whole population where as, the other events (vomiting, crying abnormal, drowsiness, appetite lost, and irritability) were planned to be evaluated only in the participants aged 6 months to \<36 months. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on the SafAS population. Here, 'number analyzed' = number of participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Within 7 days after any vaccination **Title:** Number of Participants With Solicited Systemic Reactions After Any Vaccination **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) ##### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Outcome Measure 14 **Description:** A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included: headache, malaise, myalgia and shivering. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on the SafAS population. Here, "overall number of participants analyzed"= participants evaluable for this outcome measure. Data not collected and reported for Groups 5 and 6 because none of the participants in both groups lies in the age group of \>36 months. **Reporting Status:** POSTED **Time Frame:** Within 7 days after any vaccination **Title:** Number of Participants With Solicited Systemic Reactions After Any Vaccination: Participants Aged >36 Months **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) ##### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) ##### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** OG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) ### Participant Flow Module #### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 30 microgram (μg) high-dose quadrivalent influenza vaccine (QIV-HD), intramuscularly (IM) at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** FG000 **Title:** Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years) #### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** FG001 **Title:** Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years) #### Group **Description:** Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** FG002 **Title:** Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years) #### Group **Description:** Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted standard-dose quadrivalent influenza vaccine (QIV-SD), IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** FG003 **Title:** Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years) #### Group **Description:** Participants from Canada (aged 6 to less than \[\<\] 24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** FG004 **Title:** Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months) #### Group **Description:** Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted trivalent influenza vaccine (TIV), IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. **ID:** FG005 **Title:** Group 6: Adjuvanted TIV (Canada: 6 to <24 Months) #### Period **Title:** Overall Study ##### Withdraw **Type:** Withdrawal by parent/guardian ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Protocol deviation ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 4 ###### Reason **Group ID:** FG003 **Number of Subjects:** 5 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 124 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 159 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 234 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 13 ##### Milestone **Type:** Safety Analysis Set Population (SafAS) **Comment:** SafAS: Included participants who had received at least one dose of the study vaccines. ###### Achievement **Group ID:** FG000 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 121 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 158 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 234 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 13 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 119 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 120 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 152 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 228 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 13 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 5 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 7 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 **Pre-Assignment Details:** A total of 665 participants were enrolled in the study. **Recruitment Details:** The study was conducted at 16 centers in United States (US) and Canada from 09 October 2018 to 16 October 2019. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00320879 **Brief Title:** Optimal Dose of Irbesartan for Renoprotection in Type 2 Diabetic Patients With Persistent Microalbuminuria **Official Title:** Optimal Dose of Irbesartan for Renoprotection in Type 2 Diabetic Patients With Persistent Microalbuminuria #### Organization Study ID Info **ID:** 26122284 #### Organization **Class:** OTHER **Full Name:** Steno Diabetes Center Copenhagen ### Status Module #### Completion Date **Date:** 2004-11 #### Expanded Access Info #### Last Update Post Date **Date:** 2006-05-18 **Type:** ESTIMATED **Last Update Submit Date:** 2006-05-17 **Overall Status:** COMPLETED #### Start Date **Date:** 2003-09 **Status Verified Date:** 2003-07 #### Study First Post Date **Date:** 2006-05-03 **Type:** ESTIMATED **Study First Submit Date:** 2006-05-01 **Study First Submit QC Date:** 2006-05-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Steno Diabetes Center Copenhagen ### Description Module **Brief Summary:** Aim: To evaluate the renoprotective effect as reflected by short-term changes in albuminuria of ultra high doses of irbesartan in Type 2 diabetic patients with microalbuminuria Design: A double-masked randomized cross-over trial including 60 hypertensive Type 2 diabetic patients with microalbuminuria on ongoing antihypertensive medication. At inclusion, previous antihypertensive treatment will be discontinued and replaced with bendroflumethiazide 5 mg o.d. for the entire study. Following two months wash-out (baseline), patients will be treated randomly with irbesartan 300, 600 and 900 mg o.d., each dose for two months. End-points evaluated at the end of each study period include urinary albumin excretion rate (UAE, mean of three 24-hrs collections), 24-hrs blood pressure (ABP); and GFR (51Cr-EDTA). **Detailed Description:** Aim: The primary aim of our study is to evaluate the antiproteinuric effect of irbesartan 300, 600 and 900 mg once daily in type 2 diabetic patients with microalbuminuria. Secondary to evaluate the effect on 24-h ambulatory blood pressure, glomerular filtration rate (GFR), urinary TGF beta excretion, and markers of endothelial dysfunction, and finally to evaluate the association between treatment response and genotypes with possible implications for the risk of cardiovascular disease. Patients 60 type 2 diabetic patients with persistent microalbuminuria (at least two out of three 24-h urinary collections with albumin excretion between 30 and 300 mg/24-h). Duration of study 38 weeks (8 weeks wash-out and 30 weeks of double-blind randomized cross-over (treatment with irbesartan 300, 600 and 900 mg for 10 weeks at each dose level)). Design The study consists of an eight week wash-out period followed by a double-blind randomized three 10 week treatment period cross-over trial (please see enclosed flow chart). Wash-out period: Eight weeks prior to randomization all previous antihypertensive medication is discontinued and replaced by hydrochlorothiazide 25 mg once daily throughout the entire study period. Hydrochlorothiazide is added to reduce blood pressure elevation and edema formation during the trial and to eliminate the influence of varying dietary salt intake on the effects of irbesartan during the double blind treatment periods. Double-blind cross-over periods: All patients receive treatment with irbesartan 300, 600 and 900 mg once daily in random order, without wash-out between treatment periods. All treatment periods are of 10 weeks duration. They consist of an initial two week titration period on irbesartan 300 mg o.d. to minimize the risk of adverse events including hypotension during cross-over in doses followed by an eight week period on the full dose for the given treatment level. For safety reasons blood pressure, serum potassium and serum creatinine will be measured 4 weeks after the beginning of each treatment period (two weeks after the full dose of the treatment period is reached). End-points are evaluated after the wash-out period (baseline) and at the end of each treatment period. Methods Albuminuria is assessed by turbidimetry in three 24-h urinary samples. 24-h ambulatory blood pressure by the Takeda TM-2420/2421 device. GFR by plasma clearance of 51Cr-EDTA. DNA will be extracted from a venous sample to determine genotypes with possible implications for the risk of cardiovascular disease. Initially we will evaluate the influence of the ACE/ID- , Angiotensin II type I receptor (A1166C) - and the angiotensinogen (M235T) polymorphisms. Endpoints Primary endpoint: change in albuminuria Secondary endpoints: 24-h ambulatory blood pressure, glomerular filtration rate (GFR), and to evaluate the association between treatment response genotypes with possible implications for the risk of cardiovascular disease ### Conditions Module **Conditions:** - Type 2 Diabetes - Microalbuminuria **Keywords:** - diabetes - microalbuminuria - angiotensin II receptor blockade - irbesartan - dose-response - randomized - double-blind - renin-angiotensin-aldosterone system - clinical - hypertension ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 52 **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** irbesartan **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** urinary albumin excretion rate #### Secondary Outcomes **Measure:** ambulatory blood pressure **Measure:** glomerular filtration rate **Measure:** serum potassium **Measure:** serum creatinine **Measure:** lipids **Measure:** renin **Measure:** aldosterone **Measure:** NT-proBNP **Measure:** markers of endothelial function **Measure:** markers of inflammation **Measure:** genotypes with possible implications for the risk of cardiovascular disease ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Type 2 diabetes (WHO criteria) and age above 18 years. * Persistent microalbuminuria (urinary albumin excretion between 30 and 300 mg/24-h in at least two out of three 24-urinary collections * Systolic blood pressure \> 110 mmHg Exclusion Criteria: * Serum creatinine \> 150 micromol/l * Known non-diabetic renal disease * Pregnancy or fertile women not using adequate contraception (intrauterine device, sterilization or oral anticonception) * Systolic blood pressure persistently \> 180 mm Hg or \< 100 mm Hg * Diastolic blood pressure persistently \> 105 mm Hg * Plasma potassium \> 4.8 mmol/l * Heart failure, acute myocardial infarction, unstable angina or coronary by-pass surgery within the previous three months. * Known intolerance to angiotensin II receptor blockers **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Gentofte **Country:** Denmark **Facility:** Steno Diabetes Center **State:** Copenhagen **Zip:** 2820 #### Overall Officials **Official 1:** **Affiliation:** Steno Diabetes Center, Gentofte, Denmark **Name:** Hans-Henrik Parving **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Steno Diabetes Center, Gentofte, Denmark **Name:** Kasper Rossing **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Rossing K, Schjoedt KJ, Jensen BR, Boomsma F, Parving HH. Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney Int. 2005 Sep;68(3):1190-8. doi: 10.1111/j.1523-1755.2005.00511.x. **PMID:** 16105050 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011507 - Term: Proteinuria - ID: D000014555 - Term: Urination Disorders - 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: D000020924 - Term: Urological Manifestations ### 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: BC14 - Name: Heart and Blood Diseases - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: LOW - As Found: Unknown - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M3766 - Name: Albuminuria - Relevance: HIGH - As Found: Microalbuminuria - ID: M14368 - Name: Proteinuria - Relevance: LOW - As Found: Unknown - ID: M17305 - Name: Urination Disorders - 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: M22659 - Name: Urological Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000419 - Term: Albuminuria ### Intervention Browse Module - Ancestors - ID: D000000959 - Term: Antihypertensive Agents - ID: D000047228 - Term: Angiotensin II Type 1 Receptor Blockers - ID: D000057911 - Term: Angiotensin Receptor Antagonists - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: VaCoAg - Name: Vasoconstrictor Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnAg - Name: Antihypertensive Agents ### Intervention Browse Module - Browse Leaves - ID: M4132 - Name: Angiotensin II - Relevance: LOW - As Found: Unknown - ID: M289354 - Name: Giapreza - Relevance: LOW - As Found: Unknown - ID: M4135 - Name: Angiotensinogen - Relevance: LOW - As Found: Unknown - ID: M1786 - Name: Irbesartan - Relevance: HIGH - As Found: Dietary intervention - ID: M4277 - Name: Antihypertensive Agents - Relevance: LOW - As Found: Unknown - ID: M25789 - Name: Angiotensin II Type 1 Receptor Blockers - Relevance: LOW - As Found: Unknown - ID: M28916 - Name: Angiotensin Receptor Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077405 - Term: Irbesartan ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00418379 **Brief Title:** Phase III Study to Assess the Long Term Efficacy, Carry-over Effect and Safety of 300 IR Sublingual Immunotherapy Tablets **Official Title:** A Randomised, Double-blind, Placebo-controlled, Multi-national, Multi-centre, Phase III Study to Assess the Long Term Efficacy, Carry-over Effect and Safety of Two Dosing Regimens of 300 IR Sublingual Immunotherapy (SLIT) Administered as Allergen-based Tablets Once Daily to Patients Suffering From Grass Pollen Rhinoconjunctivitis #### Organization Study ID Info **ID:** VO53.06 #### Organization **Class:** INDUSTRY **Full Name:** Stallergenes Greer ### Status Module #### Completion Date **Date:** 2011-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-05-25 **Type:** ESTIMATED **Last Update Submit Date:** 2016-04-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2016-05-25 **Type:** ESTIMATED **Results First Submit Date:** 2016-01-25 **Results First Submit QC Date:** 2016-04-18 #### Start Date **Date:** 2006-12 **Status Verified Date:** 2016-04 #### Study First Post Date **Date:** 2007-01-04 **Type:** ESTIMATED **Study First Submit Date:** 2007-01-03 **Study First Submit QC Date:** 2007-01-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Stallergenes Greer #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** A phase III study to evaluate Long term efficacy , carry-over effect and safety of 300 IR sublingual Immunotherapy (SLIT) tablets in adults patients suffering from grass pollen rhinoconjunctivitis ### Conditions Module **Conditions:** - Allergy **Keywords:** - Sublingual immunotherapy - Grass pollen tablet - Allergic rhinoconjunctivitis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 633 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 4 months before the pollen season **Intervention Names:** - Drug: 300 IR (4M) **Label:** 300 IR (4M) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 2 months before the pollen season **Intervention Names:** - Drug: 300 IR (2M) **Label:** 300 IR (2M) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Placebo tablet **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 300 IR (4M) **Description:** 300 IR grass pollen allergen extract tablet starting 4 months before the pollen season **Name:** 300 IR (4M) **Other Names:** - Sublingual immunotherapy tablet **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 300 IR (2M) **Description:** 300 IR grass pollen allergen extract tablet starting 2 months before the pollen season **Name:** 300 IR (2M) **Other Names:** - Sublingual immunotherapy tablet **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Placebo **Description:** Placebo tablet **Name:** Placebo **Other Names:** - Sublingual placebo tablet **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The Adjusted Symptom Score (AdSS) is a subject-specific symptom score which is adjusted for rescue medication use. Participants assessed daily, during the Year 3 pollen period while on treatment, 6 rhinoconjunctivitis symptoms (sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus and watery eyes) each symptom is scored as follows: 0: no symptoms, 1: mild symptoms, 2: moderate symptoms, 3: severe symptoms. The sum of the 6 symptoms is the Rhinoconjunctivitis Total Symptom Score (RTSS) (range 0-18). If the subject took rescue medication on a given day, the AdSS equals the RTSS of that day or the AdSS of the day before, whichever is higher. This adjustment applies to the day of rescue medication use and the following day. Like the RTSS, the AdSS ranges from 0 to 18. The lower the score, the better the outcome. **Measure:** Average Adjusted Symptom Score (AAdSS) **Time Frame:** Pollen period (average of 33.8 days) of Year 3 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female outpatients aged 18 to 50 years * Grass pollen-related allergic rhinoconjunctivitis for at least the last two pollen seasons * Positive SPT and specific IgE values of at least Class 2 for grass pollen allergens * A score of greater than or equal to 12 out of a possible 18 on the Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) Exclusion Criteria: * Patients with symptoms of rhinoconjunctivitis during the grass pollen season due to sensitisation to allergens other than grass pollen must not be included. Patients must be asymptomatic to all other allergens during the grass pollen season. Patients who have allergic rhinitis due to perennial allergen may not be included. * Asthma requiring treatment other than beta-2 inhaled agonists. * Patients who have received any desensitisation treatment for grass pollen or with any other allergen within the previous 5 years. **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Toulouse **Country:** France **Facility:** DIDIER **Zip:** 31400 #### Overall Officials **Official 1:** **Affiliation:** Hôpital Rangueil-Larrey, Toulouse, France **Name:** Alain DIDIER, MD, Pr **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Didier A, Worm M, Horak F, Sussman G, de Beaumont O, Le Gall M, Melac M, Malling HJ. Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis. J Allergy Clin Immunol. 2011 Sep;128(3):559-66. doi: 10.1016/j.jaci.2011.06.022. Epub 2011 Jul 29. **PMID:** 21802126 **Citation:** Didier A, Malling HJ, Worm M, Horak F, Sussman G, Melac M, Soulie S, Zeldin RK. Post-treatment efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet in adults with grass pollen-induced allergic rhinoconjunctivitis. Clin Exp Allergy. 2013 May;43(5):568-77. doi: 10.1111/cea.12100. **PMID:** 23600548 **Citation:** Didier A, Malling HJ, Worm M, Horak F, Sussman GL. Prolonged efficacy of the 300IR 5-grass pollen tablet up to 2 years after treatment cessation, as measured by a recommended daily combined score. Clin Transl Allergy. 2015 May 22;5:12. doi: 10.1186/s13601-015-0057-8. eCollection 2015. **PMID:** 26097680 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - 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: M2853 - Name: Immunomodulating Agents - Relevance: HIGH - As Found: Computer - ID: M10201 - Name: Immunologic Factors - Relevance: HIGH - As Found: Computer ### Intervention Browse Module - Meshes - ID: D000091369 - Term: Immunomodulating Agents - ID: D000007155 - Term: Immunologic Factors ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** TEAEs were defined as any AE which started on or after the administration of the investigational product (IP) in the corresponding treatment period up to 30 days after the last administration of the IP (inclusive) for the corresponding period. Note: Serious Adverse Events and Other Adverse Events are described in the Results Publications. #### Event Groups **Group ID:** EG000 **Title:** 300 IR (4M) **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 4 months before the pollen season **ID:** EG000 **Other Num Affected:** 179 **Other Num at Risk:** 207 **Serious Number Affected:** 9 **Serious Number At Risk:** 207 **Title:** 300 IR (4M) **Group ID:** EG001 **Title:** 300 IR (2M) **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 2 months before the pollen season **ID:** EG001 **Other Num Affected:** 167 **Other Num at Risk:** 207 **Serious Number Affected:** 7 **Serious Number At Risk:** 207 **Title:** 300 IR (2M) **Group ID:** EG002 **Title:** Placebo **Description:** Placebo tablet **ID:** EG002 **Other Num Affected:** 170 **Other Num at Risk:** 219 **Serious Number Affected:** 6 **Serious Number At Risk:** 219 **Title:** Placebo **Frequency Threshold:** 5 #### Other Events **Term:** THROAT IRRITATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** SNEEZING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** RHINORRHOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** NASAL DISCOMFORT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** NASAL CONGESTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** COUGH **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** PHARYNGOLARYNGEAL PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** RHINITIS ALLERGIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** ORAL PRURITUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** OEDEMA MOUTH **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** DYSPEPSIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** EYE PRURITUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** LACRIMATION INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** CONJUNCTIVITIS ALLERGIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** CONJUNCTIVITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** NASOPHARYNGITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. **Term:** RHINITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. **Term:** HEADACHE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** EAR PRURITUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** ASTHMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** PHARYNGEAL OEDEMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** ORAL DISCOMFORT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** GLOSSODYNIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** PARAESTHESIA ORAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** PHARYNGITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. **Term:** INFLUENZA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. **Term:** SEASONAL ALLERGY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA Version 9.1. **Term:** BACK PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 9.1. #### Serious Events **Term:** APPENDICITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** DIARRHOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** HEPATITIS B **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 219 **Term:** GENITAL INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** CERVICAL VERTEBRAL FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** LOWER LIMB FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 219 **Term:** CONTUSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** MENISCUS LESION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 207 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** BENIGN NEOPLASM OF CERVIX UTERI **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 207 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** TESTICULAR GERM CELL TUMOUR MIXED STAGE I **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 207 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** FAMILIAL MEDITERRANEAN FEVER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Congenital, familial and genetic disorders **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** HYPERSENSITIVITY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** INTERVERTEBRAL DISC PROTRUSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** ECTOPIC PREGNANCY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Pregnancy, puerperium and perinatal conditions **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** ANGIOEDEMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 207 **Group ID:** EG001 **Num At Risk:** 207 **Group ID:** EG002 **Num At Risk:** 219 **Term:** CONCUSSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 167 **Group ID:** EG001 **Num At Risk:** 159 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 182 **Term:** SPINAL COLUMN INJURY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 167 **Group ID:** EG001 **Num At Risk:** 159 **Group ID:** EG002 **Num At Risk:** 182 **Term:** ARTHROPATHY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 167 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 159 **Group ID:** EG002 **Num At Risk:** 182 **Term:** ABORTION INDUCED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 167 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 159 **Group ID:** EG002 **Num At Risk:** 182 **Term:** EYE INJURY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 151 **Group ID:** EG001 **Num At Risk:** 148 **Group ID:** EG002 **Num At Risk:** 166 **Term:** LIGAMENT SPRAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 151 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 148 **Group ID:** EG002 **Num At Risk:** 166 **Term:** GASTROENTERITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 151 **Group ID:** EG001 **Num At Risk:** 148 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 166 **Term:** ROAD TRAFFIC ACCIDENT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 151 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 148 **Group ID:** EG002 **Num At Risk:** 166 **Term:** RENAL COLIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 151 **Group ID:** EG001 **Num At Risk:** 148 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 166 **Term:** ASTHMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 9.1. ##### Stats **Group ID:** EG000 **Num At Risk:** 151 **Group ID:** EG001 **Num At Risk:** 148 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 166 **Time Frame:** Over 3 years during the treatment periods . ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 188 **Group ID:** BG001 **Value:** 188 **Group ID:** BG002 **Value:** 205 **Group ID:** BG003 **Value:** 581 **Units:** Participants ### Group **ID:** BG000 **Title:** 300 IR (4M) **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 4 months before the pollen season ### Group **ID:** BG001 **Title:** 300 IR (2M) **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 2 months before the pollen season ### Group **ID:** BG002 **Title:** Placebo **Description:** Placebo tablet ### Group **ID:** BG003 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 8.25 **Value:** 30.9 #### Measurement **Group ID:** BG001 **Spread:** 7.57 **Value:** 30.4 #### Measurement **Group ID:** BG002 **Spread:** 8.56 **Value:** 30.2 #### Measurement **Group ID:** BG003 **Spread:** 8.14 **Value:** 30.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 66 #### Measurement **Group ID:** BG001 **Value:** 77 #### Measurement **Group ID:** BG002 **Value:** 83 #### Measurement **Group ID:** BG003 **Value:** 226 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 122 #### Measurement **Group ID:** BG001 **Value:** 111 #### Measurement **Group ID:** BG002 **Value:** 122 #### Measurement **Group ID:** BG003 **Value:** 355 **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:** Full Analysis Set Year 1 (FASY1). FASY1 included all patients who received at least one dose of the investigational product and had at least one Adjusted Symptom Score (ASS) during the pollen period while on treatment during the Year 1. ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** Stallergenes **Phone:** +33 (0) 1 55 59 26 33 **Title:** Laurence Paolozzi, Medical Director ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** < 0.0001 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** < 0.0001 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.357 - **Upper Limit:** - **Value:** 3.39 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.369 - **Upper Limit:** - **Value:** 3.25 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.348 - **Upper Limit:** - **Value:** 5.21 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The Adjusted Symptom Score (AdSS) is a subject-specific symptom score which is adjusted for rescue medication use. Participants assessed daily, during the Year 3 pollen period while on treatment, 6 rhinoconjunctivitis symptoms (sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus and watery eyes) each symptom is scored as follows: 0: no symptoms, 1: mild symptoms, 2: moderate symptoms, 3: severe symptoms. The sum of the 6 symptoms is the Rhinoconjunctivitis Total Symptom Score (RTSS) (range 0-18). If the subject took rescue medication on a given day, the AdSS equals the RTSS of that day or the AdSS of the day before, whichever is higher. This adjustment applies to the day of rescue medication use and the following day. Like the RTSS, the AdSS ranges from 0 to 18. The lower the score, the better the outcome. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Full Analysis Set Year 3 (FASY3). FASY3 included all patients who received at least one dose of the investigational product and had at least one Adjusted Symptom Score (AdSS) during the pollen period while on treatment during the Year 3. **Reporting Status:** POSTED **Time Frame:** Pollen period (average of 33.8 days) of Year 3 **Title:** Average Adjusted Symptom Score (AAdSS) **Type:** PRIMARY **Unit of Measure:** Units on a scale (range: 0 to 18) ##### Group **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 4 months before the pollen season **ID:** OG000 **Title:** 300 IR (4M) ##### Group **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 2 months before the pollen season **ID:** OG001 **Title:** 300 IR (2M) ##### Group **Description:** Placebo tablet **ID:** OG002 **Title:** Placebo ### Participant Flow Module #### Group **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 4 months before the pollen season **ID:** FG000 **Title:** 300 IR (4M) #### Group **Description:** 300 IR grass pollen allergen extract tablet, treatment starting 2 months before the pollen season **ID:** FG001 **Title:** 300 IR (2M) #### Group **Description:** Placebo tablet **ID:** FG002 **Title:** Placebo #### Period **Title:** Year 1 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 9 ###### Reason **Group ID:** FG001 **Number of Subjects:** 15 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ###### Reason **Group ID:** FG001 **Number of Subjects:** 8 ###### Reason **Group ID:** FG002 **Number of Subjects:** 5 ##### Withdraw **Type:** Any other reason not above-mentioned ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 5 ###### Reason **Group ID:** FG002 **Number of Subjects:** 7 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 207 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 207 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 219 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 189 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 179 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 204 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 18 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 28 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 15 #### Period **Title:** Year 2 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 5 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ##### Withdraw **Type:** Any other reason not above-mentioned ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 6 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 167 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 159 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 182 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 159 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 155 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 172 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 10 #### Period **Title:** Year 3 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ##### Withdraw **Type:** Any other reason not above-mentioned ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 151 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 148 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 166 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 148 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 146 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 163 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 3 #### Period **Title:** Year 4 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ##### Withdraw **Type:** Any other reason not above-mentioned ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 145 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 141 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 156 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 142 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 136 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 154 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 5 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 2 #### Period **Title:** Year 5 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Withdraw **Type:** Any other reason not above-mentioned ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 128 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 120 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 134 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 126 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 115 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 131 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 5 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 3 **Recruitment Details:** First Patient First Visit 08 DEC 2006, Last Patient Last Visit 07 SEP 2011 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT06393179 **Brief Title:** Epidemiology and Treatment Strategy of Open Respiratory Phenotype in Critically Ill Patients **Official Title:** Epidemiology and Treatment Strategy of Open Respiratory Phenotype in Critically Ill Patients #### Organization Study ID Info **ID:** OPEN-RESPIRATORY #### Organization **Class:** OTHER **Full Name:** Southeast University, China ### Status Module #### Completion Date **Date:** 2024-08-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-01 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-27 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-08-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-30 **Type:** ESTIMATED **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-05-01 **Type:** ACTUAL **Study First Submit Date:** 2024-04-27 **Study First Submit QC Date:** 2024-04-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Southeast University, China #### Responsible Party **Investigator Affiliation:** Southeast University, China **Investigator Full Name:** Ling Liu **Investigator Title:** Director of Intensive Care Unit, Principal Investigator, Clinical Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Monitoring airway pressure is essential for patients with mechanical ventilation. However, static airway pressure does not reflect alveolar pressure at all. Airway pressure is supposed to completely interrupt the communication between proximal airway opening and the distal alveolar and/or small airway structures. In this condition, some alveoli may still be inflated but do not communicate with proximal airways and auto-PEEP will give a biased estimated of mean alveolar pressure. To be note, distinguishing the airway closure and alveolar collapse can be challenging at times. The quasi-static PV curve is a useful bedside tool to set mechanical ventilation, which may help us to identify the airway closure and alveolar collapse. Meanwhile, the quasi-static PV curve can only reflects a global behaviour of the lung, while EIT may be a useful tool to assess the regional information on airway closure and alveolar collapse. ### Conditions Module **Conditions:** - Mechanical Ventilation Pressure High - Critical Illness **Keywords:** - mechanical ventilation - airway closure - alveolar collapse ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Enrolled patients will receive a PV curve with a low-flow insufflation of 5 L/min starting from 0 cmH2O to a maximal airway pressure corresponding to the plateau pressure. **Intervention Names:** - Other: pressure-volume curve with a low-flow insufflation of 5 L/min **Label:** P-V curve group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - P-V curve group **Description:** The patient undergoes a pressure-volume curve with a low-flow insufflation of 5 L/min while in a state of analgesia, sedation, and absence of spontaneous breathing. **Name:** pressure-volume curve with a low-flow insufflation of 5 L/min **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** airway closure and alveolar collapse are monitored by PV curve with a low-flow insufflation of 5 L/min **Measure:** the rate of airway closure and alveolar collapse **Time Frame:** up to 24 hours **Description:** According to the characteristics of the low inflation point of PV curve, the respiratory open pressure phenotype was constructed **Measure:** Phenotype of respiratory open pressure **Time Frame:** up to 24 hours #### Secondary Outcomes **Description:** Respiratory system compliance is calculated as the ratio of tidal volume to the difference between plateau pressure and positive end-expiratory pressure. **Measure:** respiratory system compliance **Time Frame:** up to 24 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients undergoing controlled mechanical ventilation * The duration of endotracheal intubation \< 48 hrs Exclusion Criteria: * Severe hemodynamic instability * Severe chronic lung disease requiring long-term home oxygen therapy * Patients without analgesic sedation * Decline to participate in the study * Refusal to sign informed consent **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** ling liu, phD **Phone:** 15901599659 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** xueyan yuan, phD **Role:** CONTACT #### Locations **Location 1:** **City:** Nanjing **Country:** China **Facility:** Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University **State:** Jiangsu **Zip:** 210000 #### Overall Officials **Official 1:** **Affiliation:** Zhongda Hospital **Name:** ling liu **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - 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: M15577 - Name: Shock - Relevance: LOW - As Found: Unknown - ID: M19010 - Name: Critical Illness - Relevance: HIGH - As Found: Critical Illness - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000016638 - Term: Critical Illness ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00787579 **Brief Title:** Assessment of Bifocal and Prismatic Bifocal Spectacles for Myopia Control in Children **Official Title:** Assessment of Bifocal and Prismatic Bifocal Spectacles for Myopia Control in Children #### Organization Study ID Info **ID:** Essilor #### Organization **Class:** INDUSTRY **Full Name:** Essilor International ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2008-11-07 **Type:** ESTIMATED **Last Update Submit Date:** 2008-11-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-04 **Type:** ACTUAL #### Start Date **Date:** 2003-04 **Status Verified Date:** 2008-11 #### Study First Post Date **Date:** 2008-11-07 **Type:** ESTIMATED **Study First Submit Date:** 2008-11-04 **Study First Submit QC Date:** 2008-11-06 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Queensland University of Technology #### Lead Sponsor **Class:** INDUSTRY **Name:** Essilor International #### Responsible Party **Old Name Title:** Desmond Cheng **Old Organization:** Essilor International ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** 1. To determine if the effect of near-addition lenses (bifocals) is more prominent for children with high myopia progression. 2. To study how different subject characteristics such as age, gender, baseline degree of myopia, baseline near phoria and baseline lag of accommodation affect the efficacy of bifocal lens wear in myopic children. 3. To investigate the effect of incorporating near base-in prisms along with the near-addition lenses (prismatic bifocals) on myopia progression in myopic children. ### Conditions Module **Conditions:** - Myopia **Keywords:** - Myopia, bifocal, children ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 135 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Device: Bifocal spectacles **Label:** Bifocal spectacles **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Intervention Names:** - Device: Prismatic bifocal spectacles **Label:** Prismatic bifocals **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Label:** Single vision spectacles **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Bifocal spectacles **Description:** +1.50D bifocal spectacles **Name:** Bifocal spectacles **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Prismatic bifocals **Description:** +1.50D bifocal spectacles combined with 3Δ base-in prisms **Name:** Prismatic bifocal spectacles **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** Myopia progression, measured by cycloplegic autorefraction **Time Frame:** Every 6 months #### Secondary Outcomes **Measure:** Axial length, measured by A-scan ultrasonography **Time Frame:** Every 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age: 8 to 13 years * Myopia: -1.00 to -5.00 D * Myopia progression: at least 0.50 D/yr * Astigmatism and anisometropia: not more than 1.50 D * Distance monocular visual acuity: 6/6 or better * Near monocular visual acuity: 0.4 M or better * Stereoacuity: not more than 40 sec of arc at 40 cm Exclusion Criteria: * Strabismus * Ocular diseases **Healthy Volunteers:** True **Maximum Age:** 13 Years **Minimum Age:** 8 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Mississauga **Country:** Canada **Facility:** Dr. Desmond Cheng & Associates **State:** Ontario **Zip:** L5N 7G5 #### Overall Officials **Official 1:** **Affiliation:** Queensland University of Technology **Name:** Desmond Cheng, OD, MSc **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Cheng D, Woo GC, Drobe B, Schmid KL. Effect of bifocal and prismatic bifocal spectacles on myopia progression in children: three-year results of a randomized clinical trial. JAMA Ophthalmol. 2014 Mar;132(3):258-64. doi: 10.1001/jamaophthalmol.2013.7623. **PMID:** 24435660 **Citation:** Cheng D, Schmid KL, Woo GC, Drobe B. Randomized trial of effect of bifocal and prismatic bifocal spectacles on myopic progression: two-year results. Arch Ophthalmol. 2010 Jan;128(1):12-9. doi: 10.1001/archophthalmol.2009.332. **PMID:** 20065211 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012030 - Term: Refractive Errors - 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: M12168 - Name: Myopia - Relevance: HIGH - As Found: Myopia - ID: M14872 - Name: Refractive Errors - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009216 - Term: Myopia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04631679 **Acronym:** WASH-OUT **Brief Title:** Investigation of the Wash-out Effect of Intravenous Iron by Cell Savers (WASH-OUT) **Official Title:** Investigation of the Wash-out Effect of Intravenous Iron by Cell Savers #### Organization Study ID Info **ID:** 09-Antl-19 #### Organization **Class:** OTHER **Full Name:** University Hospital Muenster ### Status Module #### Completion Date **Date:** 2021-04-29 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-10-08 **Type:** ACTUAL **Last Update Submit Date:** 2021-09-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-04-29 **Type:** ACTUAL #### Start Date **Date:** 2019-11-08 **Type:** ACTUAL **Status Verified Date:** 2021-09 #### Study First Post Date **Date:** 2020-11-17 **Type:** ACTUAL **Study First Submit Date:** 2020-11-10 **Study First Submit QC Date:** 2020-11-10 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** University of Muenster, Institute of Inorganic and Analytical Chemistry #### Lead Sponsor **Class:** OTHER **Name:** University Hospital Muenster #### 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 study is a pilot study, which involves cardiothoracic patients. Patients, who are scheduled for elective cardiosurgical procedure, will be seen in multidisciplinary anesthesia/Patient Blood Management (PBM) clinic and screened for anemia prior to surgery. Anemic patients will eventually be treated with 500mg of ferric carboxymaltose 1 to 4 days prior to surgery. A high blood loss is expected in these procedures (\>500ml). Blood is collected and re-transfused to the patient via use of cell savers/ autologous blood restoration. The investigators will examine how fast intravenous ferric carboxymaltose is stored within the iron storage cells of the body, and how much remains within the patients blood at the time point of surgery. Next, the investigators will assess the wash out effect of iron via cell salvage. The hypothesis of this trial is that ferric carboxymaltose is washed out of the collected patient's blood by cell caver usage (Wash-Out Effect). **Detailed Description:** Because of the short time frame between iron therapy to procedure in cardiac surgery due to the need to perform cardiac revascularization, the investigators aim to investigate how much of the iron compound ferric carboxymaltose is being stored within the iron storage cells of the human body, and how much remains in the patient's own blood at the time point of surgery. The terminal elimination half-life time of ferric carboxymaltose is known to be approximately 7.1 to 12.1 hours, with peak serum ferritin levels at 48h to 120h after administration. When high blood loss in a surgical procedure is expected, such as in cardiosurgical procedures, the usage of autologous cell salvage, so called "Cell Saver", is considered standard, good practice. The blood that is lost during surgery is collected and after a specified blood separation wash, being retransfused in form of concentrated red blood cells. This trial aims to examine whether Cell Saver usage might recover high molecular iron complexes such as ferric carboxymaltose lost by bleeding intraoperatively or wash out these molecules. If amount of lost blood during surgery is too low, that Cell Saver usage would not be possible otherwise, averagely 300ml of blood from the heart-lung machine are added to the cell saver to enable the process of cell saver use. For each participant, 7 samples will be taken. The samples include patient's blood samples and samples from cell saver compartments (Washing solution, concentrates) as well as from the heart-lung-machine, in detail: 1. arterial patient's blood, preoperative, day of procedure, prior to surgery 2. blood from the heart-lung machine, intraoperative 30 minutes prior to end of use of the heart-lung machine, day of procedure 3. Cell Saver: washed-out compounds, intraoperative, after end of use of heart-lung machine, day of procedure 4. Cell Saver: produced red blood cell concentrate, intra- or postoperative, after end of use of heart-lung machine, day of procedure 5. arterial patient's blood, postoperative, day of procedure 6. venous patient's blood, 3. day postoperative 7. venous patient's blood, 7. day postoperative By liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) levels of ferric carboxymaltose are examined 1. in the patient's blood prior to surgery to determine the amount of ferric carboxymaltose within the patients blood prior to surgery, and after a certain time after the intravenous Infusion of ferric carboxymaltose (12-96 hours). 2. pre- and postoperatively and in cell saver compartments. If ferric carboxymaltose is detected in the washing solution of the Cell Saver System and not within the stored red blood cell concentrate, ferric carboxymaltose is washed out by the cell saver. ### Conditions Module **Conditions:** - Anemia - Anemia, Iron Deficiency - Iron Deficiency Anemia Treatment **Keywords:** - Anemia - Cell Saver - Iron Deficiency Anemia - Intravenous Iron - Ferric Carboxymaltose - Wash Out ### Design Module #### Bio Spec **Description:** Seven probes of patient's blood/serum, Cell Saver compounds or heart-lung machine are collected for each participant in Li-Heparin tubes (S-Monovette® 7,5ml Li-Heparin, Sarstedt AG \& Co. KG, Nümbrecht, Germany) to examine ferric carboxymaltose levels in samples from different locations and time points. **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 23 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** For Group A anemic patients (hemoglobin levels below 13g/dL in men and 12g/dL in women) with iron deficiency (transferrin saturation below 20% or ferritin serum level below 300μg/L) are screened in the Anesthesia pre-assessment clinic 1-4 days prior to cardiosurgical procedure (valve repair/implementation, aortocoronary bypass or a combination of both) and are treated with a single intravenous dose of 500 milligrams of ferric carboxymaltose in 100ml 0,9% sodium chloride solution as iron supplementation directly (FerInject® 50 mg/ml, 10 ml, Vifor Pharma Group, Switzerland). **Label:** Group A: anemic patients with iron treatment #### Arm Group 2 **Description:** For Group B, non-anemic patients (hemoglobin levels above 13g/dL in men and 12g/dL in women) without iron deficiency (transferrin saturation above 20%, ferritin serum levels above 300μg/L) are screened in the Anesthesia pre-assessment clinic 1-4 days prior to cardiosurgical procedure (valve repair/implementation, aortocoronary bypass or both combined) and are not treated with iron supplementation. **Label:** Group B: non-anemic patients without iron treatment ### Outcomes Module #### Primary Outcomes **Description:** Ferric Carboxymaltose levels in samples withdrawn from patient's blood, red blood cell concentrate of Cell Saver, heart-lung machine and washing solution prior to and after surgical procedure (µg/mL-Ferric carboxymaltose/plasma volume) **Measure:** Ferric Carboxymaltose levels (µg/mL) **Time Frame:** day of surgery to seven days after surgery #### Secondary Outcomes **Description:** Additional substitution of donor red blood cell concentrates **Measure:** Donor red blood cell concentrates **Time Frame:** Beginning till end of surgery **Description:** Ferritin levels before intravenous iron supplementation **Measure:** Ferritin (ng/ml) **Time Frame:** prior to intravenous iron supplementation **Description:** Ferritin levels after intravenous iron supplementation **Measure:** Ferritin (ng/ml) **Time Frame:** point of intravenous iron supplementation until surgery **Description:** Ferritin levels after intravenous iron supplementation **Measure:** Ferritin (ng/ml) **Time Frame:** 3 days after surgery **Description:** Ferritin levels after intravenous iron supplementation **Measure:** Ferritin (ng/ml) **Time Frame:** 7 days after surgery **Description:** Delta Hemoglobin levels between prior to IV iron substitution until surgery **Measure:** Hemoglobin levels (mg/dl) **Time Frame:** prior to intravenous iron supplementation, 1 to 4 days prior to surgery **Description:** Hemoglobin levels after surgery **Measure:** Hemoglobin levels (mg/dl) **Time Frame:** 3 days after surgery **Description:** Hemoglobin levels after surgery **Measure:** Hemoglobin levels (mg/dl) **Time Frame:** 7 days after surgery **Description:** Blood volume lost while surgical procedure **Measure:** Intraoperative blood loss (ml) **Time Frame:** Beginning till end of surgery **Description:** Delta of intraoperatively given (infusions, transfusions) and lost (bleeding, withdrawn from heart-lung machine) volumes **Measure:** Blood volume balance (ml) **Time Frame:** Beginning till end of surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * scheduled cardiosurgical procedure such as valve surgery, aortocoronary bypass or both combined within 1-4 days after anesthesiological/PBM clinic * for Group A: diagnosed anemia (hemoglobin levels below 13g/dL in men and 12g/dL in women) and iron-deficiency (transferrin saturation below 20% or ferritin serum level below 300μg/L), treatment with 500mg of ferric carboxymaltose (FerInject® 50 mg/ml, 10 ml, Vifor Pharma Group, Switzerland). Exclusion Criteria: * contraindication for intravenous iron therapy: severe infections, hepatocellular carcinoma, liver metastases, acute severe asthma, a simultaneous oral iron medication, another intravenous iron preparation, iron overload, chronic renal failure with regular intravenous iron substitution during dialysis treatment, age ≤18 years, pregnancy, lactation and being allergic to iron * elevated C-reactive protein (CRP) and leukocyte levels (cut-off level for leucocytes for men was \<10.9x10\^3/μl and for women \<12.68x10\^3/μl, respectively) **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** A total of twenty-three patients undergoing elective cardiosurgical procedures (valve surgery, aortocoronary bypass or both combined) at University Hospital of Münster, Germany. ### Contacts Locations Module #### Locations **Location 1:** **City:** Muenster **Country:** Germany **Facility:** Dept. of Anesthesiology, Intensive Care and Pain Medicine, UKM **Zip:** 48149 #### Overall Officials **Official 1:** **Affiliation:** Dept. of Anesthesiology, Intensive Care and Pain Medicine, University Hospital of Münster **Name:** Andrea U Steinbicker, MD, MPH **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006402 - Term: Hematologic Diseases - ID: D000019189 - Term: Iron Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000000747 - Term: Anemia, Hypochromic ### Condition Browse Module - Browse Branches - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M20857 - Name: Anemia, Iron-Deficiency - Relevance: HIGH - As Found: Iron Deficiency - ID: M2781 - Name: Iron Deficiencies - Relevance: HIGH - As Found: Iron Deficiency - ID: M4070 - Name: Anemia - Relevance: HIGH - As Found: Anemia - ID: M9490 - Name: Hematologic 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 ### Condition Browse Module - Meshes - ID: D000000740 - Term: Anemia - ID: D000018798 - Term: Anemia, Iron-Deficiency - ID: D000090463 - Term: Iron Deficiencies ### 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 - Abbrev: Micro - Name: Micronutrients - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: PhSol - Name: Pharmaceutical Solutions ### Intervention Browse Module - Browse Leaves - ID: M207501 - Name: Chrysarobin - Relevance: LOW - As Found: Unknown - ID: M10533 - Name: Iron - Relevance: LOW - As Found: Unknown - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00214279 **Brief Title:** MMF Monotherapy and Immune Regulation in Kidney Transplant Recipients: Part 1 Steroid Withdrawal **Official Title:** MMF Monotherapy and Immune Regulation in Kidney Transplant Recipients: Part 1 Steroid Withdrawal #### Organization Study ID Info **ID:** 2002-040 #### Organization **Class:** OTHER **Full Name:** University of Wisconsin, Madison #### Secondary ID Infos **ID:** CEL340 ### Status Module #### Completion Date **Date:** 2007-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-06-26 **Type:** ESTIMATED **Last Update Submit Date:** 2012-06-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-11 **Type:** ACTUAL #### Start Date **Date:** 2002-05 **Status Verified Date:** 2012-06 #### Study First Post Date **Date:** 2005-09-21 **Type:** ESTIMATED **Study First Submit Date:** 2005-09-14 **Study First Submit QC Date:** 2005-09-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Wisconsin, Madison #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** Part 1 of the study is to gradually withdraw steroids in a group of 50 older renal transplant recipients, converting then from the 3 drug regimen to a 2 drug regimen (cyclosporine and MMF), while carefully monitoring their graft function. 25 subjects would serve as control patients in the study and would remain on the 3 drug regimen (steroids, cyclosporine and MMF). Immunologic status will be determined before and after IS withdrawal using a delayed-type hypersensitivity (DTH) transfer test previously described in the original submission. Both the steroid withdrawal subjects and the control subjects will undergo the DTH testing throughout the 3 years of study participation. ### Conditions Module **Conditions:** - Renal Transplantation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 32 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Remain on 3-drug standard of care immunosuppression including prednisone **Label:** 1 **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Corticosteroid withdrawal / prednisone taper over 14 weeks **Intervention Names:** - Drug: Corticosteroid withdrawal **Label:** 2 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 2 **Description:** prednisone withdrawal, with maintenance mycophenolate mofetil therapy and either cyclosporine or tacrolimus **Name:** Corticosteroid withdrawal **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Incidence of Allograft rejection **Time Frame:** 3 years #### Secondary Outcomes **Measure:** Renal function as determined by serum creatinine **Time Frame:** measure after 36 months **Measure:** Allograft Survival **Time Frame:** 3 years **Description:** Research assay done to determine correlation between the status of donor specific regulation (DSR) and rates of rejection in both arms of the study. **Measure:** Immunological function as determined by Trans-vivo delayed hypersensitivity assay (TV-DTH) **Time Frame:** Day 0 (pre-transplant) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient who have received a kidney transplant during the "MMF era" * Patients who have stable graft function indicated by a serum creatinine of \< 1.8 mg/dl, or a calculated creatinine clearance of \> 50 ml/minute Exclusion Criteria: * Patients who have had \> 1 rejection episode, * Patients who have had a rejection episode within the past year; * Patients who are steroid dependent due to pre-existing disease (for example, RA or SLE **Minimum Age:** 55 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Madison **Country:** United States **Facility:** Unversity of Wisconsin **State:** Wisconsin **Zip:** 53792 #### Overall Officials **Official 1:** **Affiliation:** University of Wisconsin, Madison **Name:** Hans Sollinger, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### 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 - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Derm - Name: Dermatologic Agents ### Intervention Browse Module - Browse Leaves - ID: M14121 - Name: Prednisone - Relevance: LOW - As Found: Unknown - ID: M18961 - Name: Cyclosporine - Relevance: LOW - As Found: Unknown - ID: M6730 - Name: Cyclosporins - Relevance: LOW - As Found: Unknown - ID: M12128 - Name: Mycophenolic Acid - Relevance: LOW - As Found: Unknown - ID: M18950 - Name: Tacrolimus - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00683579 **Brief Title:** Neurocognitive Assessment in Youth Initiating HAART **Official Title:** Neurocognitive Assessment in Youth Initiating HAART #### Organization Study ID Info **ID:** ATN 071 #### Organization **Class:** OTHER **Full Name:** University of North Carolina, Chapel Hill ### Status Module #### Completion Date **Date:** 2013-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-02-28 **Type:** ACTUAL **Last Update Submit Date:** 2017-02-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-06 **Type:** ACTUAL #### Start Date **Date:** 2007-12 **Status Verified Date:** 2016-02 #### Study First Post Date **Date:** 2008-05-23 **Type:** ESTIMATED **Study First Submit Date:** 2008-05-21 **Study First Submit QC Date:** 2008-05-22 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute on Drug Abuse (NIDA) **Class:** NIH **Name:** National Institute of Mental Health (NIMH) #### Lead Sponsor **Class:** OTHER **Name:** University of North Carolina, Chapel Hill #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** ATN 071 is a prospective cohort study comparing neurocognitive functioning in four groups of youth, age 18-24: Two groups with CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml, one initiating HAART (Group 1) and the other not initiating treatment (Group 2); and two groups with CD4+ T cells \< 350 cells/mm3, one initiating treatment (Group 3) and the other not initiating treatment (Group 4). Groups 2 and 3 represent standard of care. Group 1 and a portion of group 2 will be co-enrolled in ATN 061 and will be randomly assigned to group by that protocol. ### Conditions Module **Conditions:** - HIV Infections **Keywords:** - HAART - DHHS guidelines - Treatment Naive ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 220 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants with CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml who are initiating HAART with possibility of de-intensification (early treatment). **Intervention Names:** - Drug: Early Treatment with HAART **Label:** 1 #### Arm Group 2 **Description:** Participants with CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml who are not initiating treatment. **Intervention Names:** - Other: No treatment **Label:** 2 #### Arm Group 3 **Description:** Participants with CD4+ T cells \< 350 cells/mm3 who are initiating treatment. **Intervention Names:** - Drug: HAART Treatment - standard care **Label:** 3 #### Arm Group 4 **Description:** Participants with CD4+ T cells \< 350 cells/mm3 who are not initiating treatment. **Intervention Names:** - Other: No treatment **Label:** 4 ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** HAART with possibility of de-intensification **Name:** Early Treatment with HAART **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 2 - 4 **Description:** No treatment. For group 2, participants do not yet meet DHHS guidelines. For group 4, treatment is not initiated due to unwillingness or providers' expectation of poor adherence. **Name:** No treatment **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - 3 **Description:** Initiation of HAART per DHHS guidelines, i.e. starting treatment and CD4+ T cells less than 350 cells/mm3 or HIV RNA \>100,000 copies/ml **Name:** HAART Treatment - standard care **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** The impact of early initiation of HAART on preventing neurocognitive decline in HIV infected adolescents compared to no treatment and initiation following current guidelines. **Time Frame:** 3 years #### Secondary Outcomes **Measure:** Assess youth who meet current DHHS guidelines for initiating HAART but either refuse to start HAART or are not prescribed HAART because of concerns about adherence. **Time Frame:** Baseline assessment (not longitudinal) **Measure:** To assess if de-intensification of HAART as will occur in Arm A of ATN 061 can minimally maintain neurocognitive gains made with one year of HAART. **Time Frame:** 3 years **Measure:** To assess the relationship of neurocognitive functioning to CD4+ and viral load at baseline in adolescents with HIV-1 infection (groups 1 and 2 versus 3 and 4). **Time Frame:** 3 years **Measure:** To correlate neurocognitive change with changes in CD4+ and viral loads within groups. **Time Frame:** 3 years **Measure:** To assess the incidence of HIV-associated dementia and minor cognitive-motor disorder in adolescents with risk-acquired HIV infection. **Time Frame:** 3 years **Measure:** To evaluate the relationship of current substance abuse to neurocognitive deficits in youth with risk-acquired HIV. **Time Frame:** 3 years **Measure:** To assess the relationship of neurocognitive functioning to available biomarkers within the subset of participants co-enrolled in ATN 061 (for example, immune activation markers, viral phenotype, CD4 and CD8 subsets). **Time Frame:** 3 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Groups 1 and 2 (If co-enrolling in ATN 061) * HIV positive participants age 18 years and 0 days to 24 years and 364 days (the lower age limit of this study is driven by the restriction of ATZ use to age 18 and greater); * Groups 1 and 2: CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml, as determined by two consecutive measures within 6 months of entry with the second measure being collected at pre-entry to ATN 061; * Infected with HIV after the age of nine via behavioral means; * Naïve to ART except for HAART for PMTCT for six months or less with at least six months since the time of exposure; * HIV genotype without major resistance mutations to the recommended ATV-r based HAART regimens; * Able to provide written informed consent as determined by local Institutional Review Boards; * Fluent in English or Spanish. Group 2, enrolled in ATN 071 and not ATN 061 * CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml, as determined by most recent laboratory evaluations available within 4 months prior to entry; * Not prescribed HAART according to DHHS guidelines. Groups 3 and 4: * HIV positive participants age 18 years and 0 days to 24 years and 364 days; * Infected with HIV after the of age nine via behavioral means; * Naïve to ART except for HAART for PMTCT for six months or less with at least six months since the time of exposure; * Able to provide written informed consent as determined by local Institutional Review Boards; * Fluent in English or Spanish. * CD4+ T cells \< 350 cells/mm3, as determined by most recent laboratory evaluations available within 4 months prior to entry. Group 3 ONLY: * Participant initiating HAART. Group 4 ONLY: * HAART has not been prescribed due to either participant's refusal to initiate HAART or provider's concerns about participant's predicted inability to adhere to regimen. Exclusion Criteria: Groups 1 and 2: * For Groups 1 and 2: any history of an AIDS-defining illness; * Active drug or alcohol use or dependence that, in the opinion of the site personnel, would interfere with meeting study requirements; * History of cognitive or motor impairment due to non-HIV-related conditions (for example, prematurity, cerebral palsy, closed head injury, CNS cancer or cranial irradiation, etc.) or psychosis. Youth with diagnoses of learning disabilities or attention deficit hyperactivity disorder will be allowed in the study; * Enrollment of youth with chronic or acute medical conditions other than HIV that could potentially impact upon neurocognitive functioning requires protocol chair approval. * Pregnancy at any time during the study including entry. **Maximum Age:** 24 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT **Study Population:** English or Spanish speaking youth, 18 years 0 days to 24 years 364 days, with HIV-1 infection acquired after age 9 via behavioral means, in the following immunological and treatment categories: 1. Early initiation of HAART and enrolled in 061 Arm A; CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml; 2. Initiation of HAART per DHHS guidelines (standard of care) but not yet meeting criteria. There will be 25 participants from ATN 061 preferentially enrolled into this protocol; an additional 25 participants will be enrolled with similar biomedical characteristics. 3. Initiation of HAART per DHHS guidelines (not part of ATN 061). 4. Meeting DHHS guidelines for initiating HAART, but not initiating due to unwillingness or providers' expectation of poor adherence. ### Contacts Locations Module #### Locations **Location 1:** **City:** Los Angeles **Country:** United States **Facility:** Children's Hopsital of Los Angeles **State:** California **Zip:** 90027 **Location 2:** **City:** Los Angeles **Country:** United States **Facility:** University of Southern California - IMPAACT Site **State:** California **Zip:** 90033 **Location 3:** **City:** San Francisco **Country:** United States **Facility:** University of California at San Francisco **State:** California **Zip:** 94118 **Location 4:** **City:** Aurora **Country:** United States **Facility:** Children's Hospital of Denver - IMPAACT Site **State:** Colorado **Zip:** 80045 **Location 5:** **City:** Washington **Country:** United States **Facility:** Childrens National Medical Center **State:** District of Columbia **Zip:** 20010 **Location 6:** **City:** Washington **Country:** United States **Facility:** Howard University - IMPAACT Site **State:** District of Columbia **Zip:** 20060 **Location 7:** **City:** Fort Lauderdale **Country:** United States **Facility:** Children's Diagnostic and Treatment Center **State:** Florida **Zip:** 33316 **Location 8:** **City:** Miami **Country:** United States **Facility:** University of Miami School of Medicine **State:** Florida **Zip:** 33101 **Location 9:** **City:** Tampa **Country:** United States **Facility:** University of South Florida **State:** Florida **Zip:** 33606 **Location 10:** **City:** Chicago **Country:** United States **Facility:** Stroger Hospital of Cook County **State:** Illinois **Zip:** 60612 **Location 11:** **City:** Chicago **Country:** United States **Facility:** Childrens Memorial Hospital **State:** Illinois **Zip:** 60614 **Location 12:** **City:** New Orleans **Country:** United States **Facility:** Tulane University Health Sciences Center **State:** Louisiana **Zip:** 70112 **Location 13:** **City:** Baltimore **Country:** United States **Facility:** University of Maryland **State:** Maryland **Zip:** 21201 **Location 14:** **City:** Baltimore **Country:** United States **Facility:** Johns Hopkins University - IMPAACT Site **State:** Maryland **Zip:** 21287 **Location 15:** **City:** Detroit **Country:** United States **Facility:** Children's Hospital of Michigan - IMPAACT Site **State:** Michigan **Zip:** 48201 **Location 16:** **City:** Bronx **Country:** United States **Facility:** Montefiore Medical Center **State:** New York **Zip:** 10467 **Location 17:** **City:** Manhattan **Country:** United States **Facility:** Mount Sinai Medical Center **State:** New York **Zip:** 10128 **Location 18:** **City:** Philadelphia **Country:** United States **Facility:** Childrens Hospital of Philadelphia **State:** Pennsylvania **Zip:** 19104 **Location 19:** **City:** Memphis **Country:** United States **Facility:** St. Jude Children's Research Center **State:** Tennessee **Zip:** 38105 **Location 20:** **City:** Memphis **Country:** United States **Facility:** St. Jude Children's Research Hospital - IMPAACT Site **State:** Tennessee **Zip:** 38105 **Location 21:** **City:** San Juan **Country:** Puerto Rico **Facility:** University of Puerto Rico **Zip:** 00936-5067 #### Overall Officials **Official 1:** **Affiliation:** Adolescent Trials Network **Name:** Sharon Nichols **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Kohn JN, Loop MS, Kim-Chang JJ, Garvie PA, Sleasman JW, Fischer B, Rendina HJ, Woods SP, Nichols SL, Hong S. Trajectories of Depressive Symptoms, Neurocognitive Function, and Viral Suppression With Antiretroviral Therapy Among Youth With HIV Over 36 months. J Acquir Immune Defic Syndr. 2021 Jun 1;87(2):851-859. doi: 10.1097/QAI.0000000000002653. **PMID:** 33587499 ## 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: 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: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: HIGH - As Found: HIV Infections - 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: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M10199 - Name: Immunologic Deficiency Syndromes - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015658 - Term: HIV Infections ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03633279 **Brief Title:** Treatment of Sarcopenia Improves the Muscle Mass and Muscle Strength of Patients With Liver Cirrhosis-Child C **Official Title:** Treatment of Sarcopenia Improves the Muscle Mass and Muscle Strength of Patients With Liver Cirrhosis- Child C: A Randomized Double Blind Control Trial #### Organization Study ID Info **ID:** SIMM 2018 #### Organization **Class:** OTHER **Full Name:** Dayanand Medical College and Hospital ### Status Module #### Completion Date **Date:** 2023-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-27 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-08-10 **Type:** ACTUAL #### Start Date **Date:** 2018-06-22 **Type:** ACTUAL **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2018-08-16 **Type:** ACTUAL **Study First Submit Date:** 2018-06-20 **Study First Submit QC Date:** 2018-08-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Dayanand Medical College and Hospital #### Responsible Party **Investigator Affiliation:** Dayanand Medical College and Hospital **Investigator Full Name:** Prof. Sandeep S Sidhu **Investigator Title:** Professor **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:** Sarcopenia is defined as loss of skeletal muscle mass. In cirrhosis, due to impaired urea genesis and decreased hepatic ammonia disposal, the skeletal muscle functions as a metabolic partner for the liver. The proportion of patients with sarcopenia is higher in those with alcoholic liver cirrhosis (80%) compared to cirrhosis due to other etiologies (31%-71%). Sarcopenia is prevalent in \> 50% patients with Child C cirrhosis. Sarcopenia increases the risk for severe infections in patients with cirrhosis. Adequate amino acid supply is needed for appropriate antibody and cytokine responses, that is impaired when skeletal muscle mass. The sepsis-related mortality rates in patients with and without sarcopenia are 22% and 8%, respectively (P = 0.02). In patients with liver cirrhosis is protein-calorie malnutrition, leading to severe consequences to the general state and clinical evolution of the patient. **Detailed Description:** Globally, the mortality after any infection in cirrhosis patients is very high. The cumulative mortality in patients with infections was 43.5% (11,987 patients) where as the mortality rate without infection was 13.6% (2317 patients). Over the years, variceal bleeding causing death in cirrhosis has declined substantially but there has been no improvement in infection causing mortality over several decades. It adversely affects clinical outcomes including survival, quality of life, development of other complications. Radiological image analysis is currently used to diagnose sarcopenia in cirrhosis. The European Working Group on Sarcopenia in Older People and Wilson D et al, recommend using the presence of both low muscle mass and low muscle function (strength or performance) for the diagnosis of sarcopenia. Cirrhosis is believed to be a state of anabolic resistance and standard replacement of nutrients are generally ineffective. Patients with cirrhosis frequently show protein and energy deficiency. Protein deficiency leads to hypoalbuminemia, inducing ascites and edema, whereas energy deficiency decreases fat and muscle mass and causes muscle weakness, decreasing the quality of life of patients with cirrhosis. Moreover, in patients with advanced chronic liver disease, Branched Chain Amino acids concentrations are low, whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high, conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients. The survival rate of patients with sarcopenia liver cirrhosis has been found to be significantly lower than that of non-sarcopenia cirrhotic patients. Long-term Branched Chain Amino acids supplementation significantly raises the survival rate in sarcopenia liver cirrhosis but not in non-sarcopenia liver cirrhosis showed that sarcopenia was associated with mortality in patients undergoing Live Donor Liver Transplantation, and perioperative nutritional therapy significantly improved overall survival in patients with sarcopenia. It has been reported that the longer the duration on a waiting list for liver transplantation, the more sarcopenia the patient has become, even though their Model for End-stage Liver Disease scores stay the same. Patients in an advanced state of sarcopenia are confronted by their vulnerability to infection, and ultimately their imminent death. Patients with sarcopenia tended to have postoperative complications, especially infectious complications. Studies differ on the effect of of Sarcopenia on post transplant mortality. Montano-Loza et al reported that patients with "extreme" sarcopenia exhibited significantly worse prognosis. Nevertheless, patients with severe sarcopenia must have worse prognoses because of the vulnerability to infectious problems. The main immunosuppressants used in liver transplant recipients are calcineurin inhibitors. Although liver transplant recipients usually gain weight after transplantation, that gain is mainly caused by the accumulation of fat, while skeletal muscle mass rather decreases. The state of sarcopenia rather worsen after liver transplantation. reported that sarcopenia continued to be a risk factor for mortality even in patients who managed to survive their early post transplant periods. Because sarcopenia continues, or rather worsens in some recipients, after liver transplantation, their vulnerability to infections, frailty syndrome in general, caused by sarcopenia should be seriously cautioned in addition to the problems relating to immunosuppressants. With regard to nutritional intervention for sarcopenia, Branched Chain Amino acids supplementation is vital because Branched Chain Amino acids are an essential amino acid substrate for protein synthesis and energy generation in skeletal muscles. Branched Chain Amino acids are a group of three essential amino acids comprising valine, leucine and isoleucine; these account for 35% of the essential amino acids in skeletal muscle proteins. In patients with liver cirrhosis, Branched Chain Amino acids is not only a substrate of protein synthesis and ammonia detoxification, but is also a source of energy for the skeletal muscles. Therefore, the consumption of Branched Chain Amino acids by skeletal muscle is accelerated in Liver Cirrhosis, leading to muscle protein breakdown, and resulting in sarcopenia As an effect on cirrhotic patients, Branched Chain Amino acids supplementation has been demonstrated to improve Protein Energy Malnutrition, raise serum albumin levels, and subsequently improve quality of life and prognosis The possible effect of Branched Chain Amino acids on sarcopenia is that leucine primarily activates the mammalian target of rapamycin signaling pathway involved in muscle protein synthesis, and additionally stimulates the pancreatic β cells to release insulin, which has an anabolic effect in skeletal muscle. The present study demonstrated that Branched Chain Amino acids supplementation significantly improves the prognosis of sarcopenia liver cirrhosis, but its direct effect on sarcopenia itself remains unknown. Several clinical trials have suggested that Branched Chain Amino acids supplementation improves the prognosis of cirrhotic patients. For example, a multicenter randomized trial from Italy showed that oral Branched Chain Amino acids supplementation in patients with advanced cirrhosis prevented progressive hepatic failure and improved surrogate markers and perceived health status. The standard of care for nutrition in patients with liver cirrhosis are as follows - Nutritional recommendations target the optimal supply of adequate substrates related to requirements linked to energy, protein, carbohydrates, lipids, vitamins and minerals. Based on these basic observations, patients with advanced chronic liver disease have been treated clinically with Branched Chain Amino acids-rich medicines, with positive effects. Branched Chain Amino acids will complement frequent feeding with late evening snacks in reversing muscle loss in cirrhosis. The diet combined with resistance exercises shall increase skeletal muscle mass. Clinical and laboratory Assessment Complete medical record regarding the cirrhosis, its aetiology, complications and co-morbidities will be noted. Liver Function test, Renal function test, Prothrombin time/international normalized ratio will be recorded. The severity of cirrhosis will be assessed using the Child- Pugh score and the Model of End Stage Liver Disease score. Testing- Assessment of sarcopenia Patients will participate in the following 4 procedures to measure sarcopenia: 1. L3 Skeletal Muscle Index Skeletal muscle area derived from a single slice CT has become more easily reproducible, and reduces the radiation exposure required to only 2.6 millisieverts. Measuring cross-sectional muscle area at either the level of the third (L3) or fourth (L4) lumbar vertebrae has been shown to correlate well with total body muscle mass (r = 0.71). When adjusted for patient height to take stature into account it is referred to as skeletal muscle index. Skeletal muscle index will be calculated from Slice-O-matic software, version 5 (Tomovision), Montreal, QC, Canada). Skeletal muscle index has been shown to be of higher accuracy in the diagnosis of sarcopenia in cirrhosis than anthropometry or dual-energy x-ray absorptiometry (DEXA) scanning and is now the most commonly employed method in studies investigating sarcopenia in cirrhosis. Diagnostic criteria have been extrapolated from Western cirrhosis populations. Multiple studies in cirrhosis, which have employed this definition, have produced clinically meaningful results and it is increasingly accepted as the most appropriate definition of sarcopenia when using cross-sectional imaging. 2. Muscle strength:It is assessed by grip strength and measured using a Jamar dynamometer. The summary of measures are as follow. Posture Subject seated Arm position Shoulders adducted and neutrally rotated, elbow flexed at 90°, forearm in neutral Wrist position Wrist between 0 and 30° of dorsiflexion 3. The participant will be allowed to perform one test trial. After this, three trials followed and the best score was used for analysis. Handgrip strength will be expressed in kilogram's (Kg). Three trials for each hand will be carried out and the highest value for diagnosing sarcopenia. 3. Muscle Performance \[Gait Speed Test (4-metre)\]: The test can be performed with any patient able to walk 4 meters using the instructions below: 1. Instruct the patient to walk at their normal pace. Patients may use an assistive device, if needed. 2. Ask the patient to walk down a hallway through a 1-metre zone for acceleration, a central 4-metre "testing" zone, and a 1-metre zone for deceleration (the patient should not start to slow down before the 4-metre mark). 3. Start the timer with the first footfall after the 0-metre line of the testing zone 4. Stop the timer with the first footfall after the 4-metre line of the testing zone SCORING: Gait speed of longer than 5 seconds to walk 4 meters (\<0.8 m/s) suggests an increased risk of poor muscle performance. 4. Muscle Performance-The chair stand test is a physical performance test used to assess lower-extremity function. A 5 repetition test is a measure of strength; a 10 repetition test is a measure of strength and endurance. Equipment/Set Up Use a standard chair with arms and with a seat height of approximately 17 inches for all assessments, regardless of the height of the subject. Place the back of the chair against a wall to prevent movement during the test. Procedure Instruct and demonstrate the following protocol before asking the subject to perform the test: * Sit as far back as possible in the chair seat. Keep feet firmly planted on the floor approximately hip width apart and the back of lower legs away from the chair. Keep knees bent at a 90-degree angle with arms crossed over the chest. (An individual of average or taller height will be able to sit with their upper back against the back of the chair. Individuals of shorter than average height will not be able to touch the chair back while maintaining proper position and are not required to touch the chair back during testing). * Stand up one time and sit down, returning completely to the correct starting position. * Indicate that any chair stands done with improper technique, e.g. not standing all the way up, not sitting all the way back, lifting feet off the floor, etc. will not be counted. * Allow the participant the opportunity to try one chair stand to be sure when they stand up the back of their legs are not touching the chair. * Instruct the subject that the timed assessment will begin on the command, "Ready, Set, Go" and that they are to stand up and sit back down 5 times as quickly and safely as possible. At the command "Ready, Set, Go" the tester begins timing by starting the stopwatch. * Count each chair stand out loud when the subject is in the standing position. Provide continuous verbal encouragement during the test. * At the tenth repetition click the stopwatch off while participant is in the standing position. * Conduct two trials, separated by three minutes. If subjects are unable to stand up one time without assistance than they can use their hands to assist them in rising and returning to the seated position while following all other procedures as described above. Make sure to note that hands were used when recording the assessment data. Normative value of Sarcopenia indices and association of Sarcopenia indices and mortality in child C cirrhosis patients will be also calculated. Follow up Three months after randomization, data will be collected on the 4 objective indices of sarcopenia, as outlined above.In addition, event free survival, number of hospitalisations, combined liver events (variceal bleeds, ascites , Hepato-renal syndrome, Overt Hepatic encephalopathy, Septic complications - Pneumonias, Urinary Tract Infection, spontaneous bacterial peritonitis, skin infections and septic shock) and Quality of Life (assessed using SF 36 questionnaire) will also be recorded. Monitoring for Adverse Events: Branched Chain Amino acids did not increase the risk of serious adverse events, but was associated with nausea and diarrhoea. Any adverse event will be recorded specifying the time of onset, the duration, the severity and the relationship to the test medication. Sample size: The primary objective is to show the superiority of Branched Chain Amino acids (experimental arm) versus placebo to improve both the muscle mass and muscle strength (co-primary endpoint) after 3 month of treatment in patients with sarcopeniacirrhosis (Child C) treated with standard nutrition and exercises. The co-primary endpoint is the 3-month change in CT Skeletal muscle index and Hand Grip Strength (i.e difference between the baseline and 3 month values). The study success will be only declared if both primary endpoints are statistically significant in favor of the experimental arm at two-sided significant level of 0.05. The sample size will determined as the maximum value of the sample sizes separately calculated for each endpoint with a 90% power for each comparison (considering independence between the two primary outcome as conservative approach) in order to guarantee a power of 0.80 to show the treatment efficacy on both primary outcomes. As analyzing the changes or values at 3 months are equivalent since the primary analysis will be adjusted for baseline values,Investigator determined the sample size using the 3-month values for each primary endpoints obtained in a study carried out in our center. In control arm, Investigator expect a mean CT Skeletal muscle index of 45.4±5.9 at 3-months and Mean Hand Grip Strength of 33.7+9. Compared to placebo Investigator expect that Branched Chain Amino acids will be associated with an increasing in 10% in mean value of CT Skeletal muscle index (i.e. an absolute mean difference of 4.5) and with an increasing in 20% in mean value of Hand Grip Strength (i.e. an absolute mean difference of 6.7). With a two-sided test (alpha=5%, power=90%), 38 patients per arm will be required to detect the effect size on CT Skeletal muscle index (assuming a standard deviation of 5.9) and 45 per arm to detect the effect size on Hand Grip Strength (assuming a standard deviation of 9.6). Thus, a total of 90 patients will be required. To account for an anticipated attrition rate of 20%, a total of 114 patients will be included and randomized. Statistical Analysis Plan Statistical analyses will be independently performed by the Biostatistics Department of University of Lille under the responsibility of Professor Alain Duhamel. Data will be analyzed using the SAS software (SAS Institute Inc, Cary, NC, USA) and all statistical tests will be performed with a 2-tailed alpha risk of 0.05. A detailed statistical analysis plan will be written and finalized prior to the database lock. All analyses will be performed for all randomized patients based on their original group of randomization, regardless of the treatment they actually received, study eligibility, or compliance post randomization, according to the intention-to-treat principle. Nis planned Baseline characteristics will be described for each arm. Quantitative variables will be expressed as mean (standard deviation), median (interquartile range) and range. Qualitative variables will be expressed as frequencies and percentages. Normality of distribution will be assessed graphically and using the Shapiro-Wilk test. Co-Primary outcome The change in CT Skeletal muscle index and Hand Grip Strength from baseline to 3 months will be estimated and compared between the 2 arms using the constrained longitudinal data analysis model that was proposed by Liang and Zeger. The constrained longitudinal data analysis model will be used for its potential advantages compared to a conventional longitudinal analysis of covariance (ANCOVA) model. In the constrained longitudinal data analysis, both the baseline and post baseline values are modeled as dependent variables using a linear mixed model (an unstructured covariance pattern model), and the true baseline means are constrained to be the same for the 2 treatment arms. Hence, the constrained longitudinal data analysis provides an adjustment for observed baseline differences in estimating treatment effects, using all available baseline and post-baseline values. The mean between-group difference (with a 95% confidence interval(CI)) in the 3-month change in CT Skeletal muscle index and Hand Grip Strength (BCAA vs. placebo) will be estimated as an effect size with the time-by-group interaction. If normality of the model residuals is not satisfied, nonparametric analysis will be used; absolute changes between baseline and 3-month visits will be calculated and compared between the 2 arms using a non-parametric analysis of covariance that is adjusted for baseline values. The efficacy of Branched chain amino acids will be declared only if the comparison in both primary outcome is significant at p\<0.05 (two-sided test). Missing values in CT Skeletal muscle index and Hand Grip Strength measures will be handled with a multiple imputation procedure. Missing data will be imputed under the missing at random assumption (whatever the reason for missing data) by using regression switching approach (a chained equation with m=20 imputations), with the predictive mean matching method for continuous variables, and logistic regression models (binary, ordinal or polynomial) for categorical variables. The imputation procedure will be performed using main baseline characteristics and allocated arm. Treatment effect estimates that are obtained from multiple imputed data sets will be combined using Rubin's rules. Sensitivity analyses will be conducted on the observed data (case-complete analysis) and in per-protocol population. The per-protocol population will include all randomised patients who remain eligible for the study and will be 80% compliant to the allocated treatment. Any patients who will withdraw from the trial or treatment or who will not receive the allocated treatment will be excluded for per-protocol population. Secondary outcomes The same strategy employed to analyze the co-primary outcome will be used to compare the 3-month change in muscle performance (Measured by change in Chair Stand and Gait Velocity) and the 3-month change in SF 36 - patient-reported outcome. 3-month event-free survival will be estimated using Kaplan-Meier method treating death or complications of cirrhosis as a combined events. The treatment effect will be estimated by calculating Hazard ratio (HR) and its 95% CI by using a Cox proportional hazards regression model including centers as random effect (frailty model). The proportional hazards assumption will be assessed by plotting the scaled Schoenfeld residuals of treatment effect against the rank of survival time. Adverse events will be analyzed using descriptive analysis. ### Conditions Module **Conditions:** - Liver Cirrhosis ### 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:** 96 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Branched Chain amino acid 10 grams packet (L-Isoleucine (952 Mg), L-Leucine (1904 Mg.), L-Valine(1144 Mg). one packet at 6pm and two at 9pm. **Intervention Names:** - Drug: Branched chain amino acid **Label:** Branched Chain Amino Acid **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Equinitrogenous amount of lactoalbumin 2.1 grams, and equicaloric amount with 4.0 g saccharose and 3.0 g mannitol for a total of 33.6 kcal/packet.(one packet at 6pm and two at 9pm) **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Branched Chain Amino Acid **Description:** Branched chain amino acid 10 grams packet (L-Isoleucine (952 Mg), L-Leucine (1904 Mg.), L-Valine(1144 Mg). **Name:** Branched chain amino acid **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** an equinitrogenous amount of lactoalbumin 2.1 grams, and equicaloric amount with 4.0 g saccharose and 3.0 g mannitol for a total of 33.6 kcal/packet.(one packet at 6pm and two at 9pm) **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Change in CT Skeletal muscle index (cm2/m2) (i.e difference between the baseline and 3 month values) **Measure:** Change in CT Skeletal muscle index (cm2/m2) **Time Frame:** 3 month **Description:** 3-month change in Hand Grip Strength (Kilogram) (calculated as the difference between the baseline and 3-month values obtained by Hand Grip Dynamometer) **Measure:** Change in Hand Grip Strength (Kilograms) **Time Frame:** 3 month #### Secondary Outcomes **Description:** 3-month change in muscle performance assessed by change in Gait Velocity (m/min) **Measure:** Change in muscle performance **Time Frame:** 3 month **Description:** 3-month event-free survival at 3 months (events including complications of Cirrhosis i.e. Hepatic encephalopathy, Ascites and edema, Variceal Hemorrhage, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome) **Measure:** Event-free survival **Time Frame:** 3 month **Description:** Change in health related quality of life measure by Short Form Health Survey (SF 36) QUESTIONNAIRE **Measure:** Change in Quality of life: SF 36 Scale **Time Frame:** 3 month **Description:** Change in muscle performance assessed by improvement in Chair Stand. **Measure:** Change in muscle performance **Time Frame:** 3 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Cirrhosis as diagnosed by clinical, biochemical, radiological or histologic criteria Cirrhosis - Child C class (10 - 15 score) 2. L3 SMI value \< 45.4 3. Hand Grip Strength \< 33.67 Exclusion Criteria: 1. Patients with hepatocellular carcinoma, in hepatic coma, with acquired immunodeficiency syndrome, with renal or pancreatic insufficiency, receiving enteral nutrition or being pregnant, **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:** Ludhiana **Country:** India **Facility:** Dayanand Medical College and Hospital **State:** Punjab **Zip:** 141001 #### Overall Officials **Official 1:** **Affiliation:** Dayanand Medical College and Hospital, Ludhiana, Punjab, India **Name:** Sandeep s Sidhu, DM **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Kim G, Kang SH, Kim MY, Baik SK. Prognostic value of sarcopenia in patients with liver cirrhosis: A systematic review and meta-analysis. PLoS One. 2017 Oct 24;12(10):e0186990. doi: 10.1371/journal.pone.0186990. eCollection 2017. **PMID:** 29065187 **Citation:** Kim HY, Jang JW. Sarcopenia in the prognosis of cirrhosis: Going beyond the MELD score. World J Gastroenterol. 2015 Jul 7;21(25):7637-47. doi: 10.3748/wjg.v21.i25.7637. **PMID:** 26167066 **Citation:** Wong CH, Weiss D, Sourial N, Karunananthan S, Quail JM, Wolfson C, Bergman H. Frailty and its association with disability and comorbidity in a community-dwelling sample of seniors in Montreal: a cross-sectional study. Aging Clin Exp Res. 2010 Feb;22(1):54-62. doi: 10.1007/BF03324816. Epub 2009 Nov 25. **PMID:** 19940555 **Citation:** Merli M, Lucidi C, Giannelli V, Giusto M, Riggio O, Falcone M, Ridola L, Attili AF, Venditti M. Cirrhotic patients are at risk for health care-associated bacterial infections. Clin Gastroenterol Hepatol. 2010 Nov;8(11):979-85. doi: 10.1016/j.cgh.2010.06.024. Epub 2010 Aug 12. **PMID:** 20621200 **Citation:** Roubenoff R. Sarcopenia: effects on body composition and function. J Gerontol A Biol Sci Med Sci. 2003 Nov;58(11):1012-7. doi: 10.1093/gerona/58.11.m1012. **PMID:** 14630883 **Citation:** Montano-Loza AJ, Meza-Junco J, Prado CM, Lieffers JR, Baracos VE, Bain VG, Sawyer MB. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol. 2012 Feb;10(2):166-73, 173.e1. doi: 10.1016/j.cgh.2011.08.028. Epub 2011 Sep 3. **PMID:** 21893129 **Citation:** Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol. 2016 Dec;65(6):1232-1244. doi: 10.1016/j.jhep.2016.07.040. Epub 2016 Aug 8. **PMID:** 27515775 **Citation:** Wilson D, Jackson T, Sapey E, Lord JM. Frailty and sarcopenia: The potential role of an aged immune system. Ageing Res Rev. 2017 Jul;36:1-10. doi: 10.1016/j.arr.2017.01.006. Epub 2017 Feb 20. **PMID:** 28223244 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000009133 - Term: Muscular Atrophy - ID: D000020879 - Term: Neuromuscular Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000001284 - Term: Atrophy - ID: D000020763 - Term: Pathological Conditions, Anatomical ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M11103 - Name: Liver Cirrhosis - Relevance: HIGH - As Found: Liver Cirrhosis - ID: M28396 - Name: Sarcopenia - Relevance: HIGH - As Found: Sarcopenia - 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 - ID: M12090 - Name: Muscular Atrophy - Relevance: LOW - As Found: Unknown - ID: M4589 - Name: Atrophy - Relevance: LOW - As Found: Unknown - ID: M22619 - Name: Neuromuscular Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M22519 - Name: Pathological Conditions, Anatomical - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008103 - Term: Liver Cirrhosis - ID: D000055948 - Term: Sarcopenia - ID: D000005355 - Term: Fibrosis ### Intervention Browse Module - Browse Branches - Abbrev: NaAg - Name: Natriuretic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hemat - Name: Hematinics - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M11342 - Name: Mannitol - Relevance: LOW - As Found: Unknown - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: T10 - Name: Leucine - Relevance: LOW - As Found: Unknown - ID: T23 - Name: Valine - Relevance: LOW - As Found: Unknown - ID: T9 - Name: Isoleucine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02884479 **Brief Title:** An Open-Label Phase I/II Clinical Study of PT-112 in Combination With Docetaxel in Subjects With Advanced Solid Tumor in a Phase I Dose Escalation Study and in Subjects With Non-Small Cell Lung Cancer (NSCLC) in a Phase II Dose Confirmation Study **Official Title:** An Open-Label Phase I/II Clinical Study of PT-112 in Combination With Docetaxel in Subjects With Advanced Solid Tumor in a Phase I Dose Escalation Study and in Subjects With Non-Small Cell Lung Cancer (NSCLC) in a Phase II Dose Confirmation Study #### Organization Study ID Info **ID:** SCI-PT112-ONC-P1-001 #### Organization **Class:** INDUSTRY **Full Name:** SciClone Pharmaceuticals ### Status Module #### Completion Date **Date:** 2019-03 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2018-04-25 **Type:** ACTUAL **Last Update Submit Date:** 2018-04-23 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-12 **Type:** ESTIMATED #### Start Date **Date:** 2016-08 **Status Verified Date:** 2018-03 #### Study First Post Date **Date:** 2016-08-31 **Type:** ESTIMATED **Study First Submit Date:** 2016-08-17 **Study First Submit QC Date:** 2016-08-30 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Parexel **Class:** OTHER **Name:** National Cheng-Kung University Hospital #### Lead Sponsor **Class:** INDUSTRY **Name:** SciClone Pharmaceuticals International (Cayman) Development Limited #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to test PT-112 in Combination with Docetaxel in Subjects with Advanced Solid Tumor in a Phase I Dose Escalation Study and in Subjects with Non-Small Cell Lung Cancer. ### Conditions Module **Conditions:** - Advanced Solid Tumor - Non-Small Cell Lung Cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 75 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Increasing doses of intravenously administered PT-112 in combination with 60 mg/m2 docetaxel every 3 weeks (Q3W) in subjects with advanced solid tumor of any histological type. **Intervention Names:** - Drug: PT-112 - Drug: Docetaxel **Label:** PT-112 + Docetaxel **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - PT-112 + Docetaxel **Description:** Increasing doses of intravenously administered PT-112 in combination with 60 mg/m2 docetaxel every 3 weeks (Q3W) in subjects with advanced solid tumor of any histological type. **Name:** PT-112 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - PT-112 + Docetaxel **Description:** Increasing doses of intravenously administered PT-112 in combination with 60 mg/m2 docetaxel every 3 weeks (Q3W) in subjects with advanced solid tumor of any histological type. **Name:** Docetaxel **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** dose-limiting toxicities (DLTs) **Time Frame:** Day 0 to Day 28 **Measure:** area under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) **Time Frame:** Cycle 1, Day 1: Pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 5, 8, 12, 24 hours post dose Cycle 1, Day 8: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24 hours post dose Cycle 2, Day 8: Pre-dose, 1, 2, 4 hours post dose Cycle 3 & 4, Day 8: Pre-dose #### Secondary Outcomes **Measure:** Adverse Events **Time Frame:** Cycle 1: Day 1, Day 8, Day 15; Cycle 2: Day 1, Day 8; Follow up: 30 days post final dose ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Male or female ≥ 20 years of age on the day of signing informed consent. 2. Subjects with advanced tumor of any histological type and meet the following eligibility criteria for the corresponding part of the study: * In Part 1, the subjects who failed at least one prior therapy must have pathologically confirmed advanced solid tumor of any histological type with preference of subjects with advanced NSCLC and either no available, or intolerable to, standard of-care treatment. * In Part 2, the subjects must have pathologically confirmed advanced NSCLC. Subjects are required to have evidence of measurable disease per RECIST v1.1. 3. Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1. 4. Subject must have adequate organ function as indicated by the following laboratory values: * Absolute neutrophil count (ANC) ≥ 1.5 × 109/L. * Platelets ≥ 100 × 109/L. * Hemoglobin ≥ 90 g/L or 5.6 mmol/L. * Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or calculated or directly measured creatinine clearance ≥ 60% lower limit of normal (LLN). * Serum total bilirubin ≤ 1.5 × ULN (subjects with Gilbert's Syndrome are allowed if direct bilirubin is within normal limits). * Aspartate aminotransferase (AST \[SGOT\]) and/or alanine aminotransferase (ALT \[SGPT\]) ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases. * International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN. * Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. * Albumin ≥ 3 mg/dL. 5. Female subjects are eligible to enter and participate in the study if they are of: * 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 * is post-menopausal (total cessation of menses for ≥ 1 year) * Childbearing potential, have a negative serum pregnancy test at screening (within 7 days of the first investigational product administration), are not breast feeding, and use adequate contraception before study entry and throughout the study until 180 days after the last investigational product administration. Adequate contraception, when used consistently and in accordance with both the product label and the instructions of the physician, are defined as follows: * Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female. * Any intra-uterine device with a documented failure rate of less than 1% per year. * Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; or diaphragm with spermicide; or male condom and diaphragm. 6. Male subjects are eligible to enter and participate in the study if they are vasectomized or agree to use of contraception during the study treatment period and for at least 180 days after the last dose of the study drug. 7. Willing and able to provide written informed consent and comply with the requirements of the study. Exclusion Criteria: * Subjects meeting any of the following criteria are ineligible for participation in the study: 1. Any cytotoxic chemotherapy within 21 days, prior to initiation of study drug. 2. Receipt of more than three prior regimens of cytotoxic chemotherapy (immunotherapy and targeted therapy will not be counted as a line of therapy). 3. History of hypersensitivity reaction to docetaxel and polysorbate 80 or any of its components. 4. Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of alopecia, that has not resolved to Grade 1, as determined by National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. 5. Evidence of peripheral neuropathy of Grade 2 or greater within 28 days prior to initiation of dosing. 6. Symptomatic brain metastasis requiring active treatment. 7. Bone marrow reserve which, in the clinical judgment of the Principal Investigator, is not adequate for participation in this study. 8. Known allergy or hypersensitivity to Pt-containing agents, or known intolerance to a prior Pt-containing agent which, in the judgment of the Principal Investigator, precludes re-exposure to a Pt-containing agent. 9. Radiotherapy within 28 days prior to baseline and/or receipt of radiotherapy to \>25 % of bone marrow volume. 10. Major surgery within 28 days prior to initiation of study drug combination. 11. Life expectancy \<12 weeks. 12. Active or clinically unstable bacterial, viral, or fungal infection requiring systemic therapy. 13. Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness. 14. Clinically significant hearing impairment, as judged by the Principal Investigator. 15. Any of the following within 3 months prior to initiation of study drug: uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4, APPENDIX 2), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism. 16. Unstable cardiac dysrhythmias or persistent prolongation of the QTc (Fridericia) interval to \>450 msec for males or \>470 msec for females. 17. In Part 2, any previous malignancy, except for non squamous-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumor was successfully treated with curative intent more than two years prior to study entry. 18. Use of any investigational agents within 28 days prior to the screening. 19. Pregnant or lactating female. **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Crystal Qin, M.D, Ph.D **Phone:** 86-21-2319 3802 **Role:** CONTACT #### Locations **Location 1:** **City:** Changhua County **Contacts:** ***Contact 1:*** - **Name:** Chien-Te Li - **Role:** CONTACT ***Contact 2:*** - **Name:** Chien-Te Li - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Taiwan **Facility:** Changhua Christian Hospital **Status:** RECRUITING **Location 2:** **City:** Taichung **Contacts:** ***Contact 1:*** - **Name:** Te-Chun Hsia - **Role:** CONTACT ***Contact 2:*** - **Name:** Te-Chun Hsia - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Taiwan **Facility:** China Medical University & Hospital **Status:** NOT_YET_RECRUITING **Location 3:** **City:** Tainan City **Contacts:** ***Contact 1:*** - **Name:** Wu-Chou Su - **Role:** CONTACT ***Contact 2:*** - **Name:** Wu-Chou Su - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Taiwan **Facility:** National Cheng Kung University Hospital **Status:** RECRUITING **Location 4:** **City:** Taipei City **Contacts:** ***Contact 1:*** - **Name:** Ching-Lian Ho - **Role:** CONTACT ***Contact 2:*** - **Name:** Ching-Lian Ho - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Taiwan **Facility:** Tri-Service General Hospital **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** National Cheng-Kung University Hospital **Name:** Wu-Chou Su **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** YES ## Derived Section ### Condition Browse Module - Ancestors - 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 - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: HIGH - As Found: Lung Cancer - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: HIGH - As Found: Non-Small Cell Lung Cancer - ID: M5534 - Name: Carcinoma - 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 ### Condition Browse Module - Meshes - ID: D000008175 - Term: Lung Neoplasms - ID: D000002289 - Term: Carcinoma, Non-Small-Cell Lung ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000050257 - Term: Tubulin Modulators - ID: D000050256 - Term: Antimitotic Agents - ID: D000050258 - Term: Mitosis Modulators - 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: M1668 - Name: Docetaxel - Relevance: HIGH - As Found: Physical - ID: M26197 - Name: Tubulin Modulators - Relevance: LOW - As Found: Unknown - ID: M26196 - Name: Antimitotic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077143 - Term: Docetaxel ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00699179 **Acronym:** EFFECTIVE **Brief Title:** Observational Study to Evaluate the Efficacy and Safety of NovoMix® 30 in Type 1 and 2 Diabetes **Official Title:** EFFicacious glycaEmia Control, Treatment Goal achIevement Very simplE With NovoMix 30: A Single-country, Multicentre, Prospective, Open Label, Non-controlled, Observational, 26-week Study in Serbian Patients Using NovoMix® 30 (Biphasic Insulin Aspart 30) for Treatment of Diabetes Mellitus in Everyday Clinical Practice #### Organization Study ID Info **ID:** BIASP-3557 #### Organization **Class:** INDUSTRY **Full Name:** Novo Nordisk A/S ### Status Module #### Completion Date **Date:** 2009-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-10-31 **Type:** ESTIMATED **Last Update Submit Date:** 2016-10-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-09 **Type:** ACTUAL #### Start Date **Date:** 2008-06 **Status Verified Date:** 2016-10 #### Study First Post Date **Date:** 2008-06-17 **Type:** ESTIMATED **Study First Submit Date:** 2008-06-13 **Study First Submit QC Date:** 2008-06-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Novo Nordisk A/S #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is conducted in Europe. This observational study is aimed to reflect the post-authorisation experience with insulin analogue (biphasic insulin aspart 30) when used under normal clinical practice conditions in Serbia. ### Conditions Module **Conditions:** - Diabetes - Diabetes Mellitus, Type 1 - Diabetes Mellitus, Type 2 ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 2308 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: biphasic insulin aspart 30 **Label:** A ### Interventions #### Intervention 1 **Arm Group Labels:** - A **Description:** There is no intervention in this trial. The trial is prepared to be non-interventional one. Start dose and frequency to prescribed by the physician as a result of a normal clinical evaluation. **Name:** biphasic insulin aspart 30 **Other Names:** - NovoMix® 30 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Change in HbA1c from baseline **Time Frame:** After 6 months #### Secondary Outcomes **Measure:** Percentage of patients achieving HbA1c below 7,5% for Type 1 Diabetes Mellitus, below 7.0% and below or equal to 6.5% for Type 2 Diabetes Mellitus **Time Frame:** after 12 weeks and 26 weeks compared to baseline **Measure:** Change in FPG (glucose variability) **Time Frame:** after 12 weeks and 26 weeks compared to baseline **Measure:** Change in PPG (postprandial control) **Time Frame:** after 12 weeks and 26 weeks compared to baseline **Measure:** Change in insulin dose and number of injections **Time Frame:** at 12 weeks and 26 weeks of treatment **Measure:** Change in oral antidiabetic drug therapy dosage and eventual discontinuation of oral antidiabetic drug therapy during the study **Time Frame:** after 12 weeks and 26 weeks of treatment compared to baseline **Measure:** Change in body weight and waist circumference **Time Frame:** at 12 weeks and 26 weeks of treatment compared to baseline **Measure:** Change in number of major hypoglycaemic events during 4 weeks proceeding routine visits **Time Frame:** at 12 weeks and 26 weeks of treatment compared to baseline **Measure:** Number of adverse drug reactions (ADR) **Time Frame:** after 12 weeks and 26 weeks of treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Type 1 or Type 2 Diabetes Mellitus inadequately controlled on human insulin therapy lasting for at least 6 months * HbA1c greater than 7% * Informed Consent Exclusion Criteria: * Patients with a hypersensitivity to biphasic insulin aspart 30 or to any of the excipients * Other limiting conditions specified in the locally approved NovoMix 30 SPC ( Summary of Product Characteristics), PIL ( Patient Information Leaflet). * Women who are pregnant, breast feeding or have the intention of becoming pregnant within next couple of months **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Type 1 and 2 diabetes ### Contacts Locations Module #### Locations **Location 1:** **City:** Belgrade **Country:** Former Serbia and Montenegro **Facility:** Novo Nordisk Investigational Site **Zip:** 11 070 #### Overall Officials **Official 1:** **Affiliation:** Novo Nordisk A/S **Name:** Global Clinical Registry (GCR, 1452) **Role:** STUDY_DIRECTOR ### References Module #### See Also Links **Label:** Clinical Trials at Novo Nordisk **URL:** http://novonordisk-trials.com ## 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 Mellitus - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Diabetes Mellitus, Type 2 - ID: M7117 - Name: Diabetes Mellitus, Type 1 - Relevance: HIGH - As Found: Diabetes Mellitus, Type 1 - 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: D000003924 - Term: Diabetes Mellitus, Type 2 - ID: D000003922 - Term: Diabetes Mellitus, Type 1 ### 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: Coag - Name: Coagulants ### 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: M29801 - Name: Insulin Aspart - Relevance: HIGH - As Found: Childhood - ID: M29799 - Name: Biphasic Insulins - Relevance: HIGH - As Found: Importance - ID: M14342 - Name: Protamines - Relevance: LOW - As Found: Unknown - ID: M350709 - Name: Insulin aspart, insulin aspart protamine drug combination 30:70 - Relevance: HIGH - As Found: Differential - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000061267 - Term: Insulin Aspart - ID: D000061265 - Term: Biphasic Insulins - ID: C000557564 - Term: Insulin aspart, insulin aspart protamine drug combination 30:70 ### Misc Info Module #### Removed Countries - Country: Serbia - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00038779 **Brief Title:** Blood Transplantation for Patients With Hematologic Malignancies or Bone Marrow Failure States **Official Title:** Megadose T-cell Depleted HLA-nonidentical Blood Progenitor Cell Transplantation for Patients With Hematologic Malignancies or Bone Marrow Failure States #### Organization Study ID Info **ID:** DM96-122 #### Organization **Class:** OTHER **Full Name:** M.D. Anderson Cancer Center ### Status Module #### Completion Date **Date:** 2004-09-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-10-30 **Type:** ACTUAL **Last Update Submit Date:** 2018-10-29 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2004-09-20 **Type:** ACTUAL #### Start Date **Date:** 1996-08-14 **Type:** ACTUAL **Status Verified Date:** 2018-10 #### Study First Post Date **Date:** 2002-06-07 **Type:** ESTIMATED **Study First Submit Date:** 2002-06-05 **Study First Submit QC Date:** 2002-06-06 **Why Stopped:** Lack of Accrual ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** M.D. Anderson Cancer Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to assess early treatment failure within 100 days and to assess the effect of this regimen on engraftment, GVHD, immune recovery, relapse of malignancy and survival. ### Conditions Module **Conditions:** - Leukemia - Non Hodgkin's Lymphoma - Aplastic Anemia **Keywords:** - Lymphoma - CML - CLL - AML - ALL - MDS - AA ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 7 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: Megadose T-cell Depleted HLA-nonidentical Blood Progenitor Cell Transplantation **Label:** Megadose T cell depleted **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Megadose T cell depleted **Name:** Megadose T-cell Depleted HLA-nonidentical Blood Progenitor Cell Transplantation **Type:** PROCEDURE ### Eligibility Module **Eligibility Criteria:** * Patients with acute leukemia, lymphoma that failed to respond or relapsed after chemotherapy or CML beyond first chronic phase. * Patients with aplastic anemia or myelodysplasia which failed to respond to primary therapy are eligible. * Patients with low grade lymphoma or CLL will only be eligible if they failed two chemotherapy regimens and have stage IV disease. * Patients must be \<age 50 with a related haploidentical donor (phenotypically one, two or three HLA A, B and DR antigen mismatched) donor. * Patients should have adequate hepatic and renal function with a bilirubin of less than or equal to 1.5mg%, SGPT less than or equal to 3x the upper limits of normal, and creatine less than or equal to 1.5mg%. * Patients with serious intercurrent medical illness are not eligible. * Patients and their donors must provide written informed consent. **Maximum Age:** 49 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Houston **Country:** United States **Facility:** MD Anderson Cancer Center **State:** Texas **Zip:** 77030 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000006402 - Term: Hematologic Diseases - ID: D000000740 - Term: Anemia - ID: D000001855 - Term: Bone Marrow Diseases - ID: D000095542 - Term: Cytopenia ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: LOW - As Found: Unknown - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: M4071 - Name: Anemia, Aplastic - Relevance: HIGH - As Found: Aplastic Anemia - ID: M4070 - Name: Anemia - Relevance: LOW - As Found: Unknown - ID: M21314 - Name: Hematologic Neoplasms - Relevance: HIGH - As Found: Hematologic Malignancies - ID: M13118 - Name: Pancytopenia - Relevance: HIGH - As Found: Bone Marrow Failure - ID: M2241 - Name: Bone Marrow Failure Disorders - Relevance: HIGH - As Found: Bone Marrow Failure - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M5134 - Name: Bone Marrow Diseases - Relevance: LOW - As Found: Unknown - ID: M3170 - Name: Cytopenia - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown - ID: T460 - Name: Aplastic Anemia - Relevance: HIGH - As Found: Aplastic Anemia ### Condition Browse Module - Meshes - ID: D000019337 - Term: Hematologic Neoplasms - ID: D000000741 - Term: Anemia, Aplastic - ID: D000080983 - Term: Bone Marrow Failure Disorders - ID: D000010198 - Term: Pancytopenia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00361179 **Brief Title:** Long Term Effects of Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C/B Co-Infection and Chronic Hepatitis C **Official Title:** An Extension, Observational Protocol to Evaluate the Long Term Effects of Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C/B Co-Infection and Chronic Hepatitis C in the Original Study ML17862 #### Organization Study ID Info **ID:** 9561706020 #### Organization **Class:** OTHER **Full Name:** National Taiwan University Hospital ### Status Module #### Completion Date **Date:** 2011-12 #### Expanded Access Info #### Last Update Post Date **Date:** 2006-08-07 **Type:** ESTIMATED **Last Update Submit Date:** 2006-08-04 **Overall Status:** COMPLETED #### Start Date **Date:** 2006-05 **Status Verified Date:** 2006-08 #### Study First Post Date **Date:** 2006-08-07 **Type:** ESTIMATED **Study First Submit Date:** 2006-08-04 **Study First Submit QC Date:** 2006-08-04 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Hoffmann-La Roche #### Lead Sponsor **Class:** OTHER **Name:** National Taiwan University Hospital ### Description Module **Brief Summary:** Chronic hepatitis C may relapse in simple chronic hepatitis C patients who initially obtained sustained virologic responses. Although the HCV SVR could be maintained in around 90%, the remaining 10% of these patients may develop hepatitis C relapse during follow-up. Therefore, it is important to follow up the long-term of these patients with dual chronic hepatitis B and C. From another aspect, for the treatment of chronic hepatitis B, the virologic and serologic responses may also not be durable. Alternatively, previous studies suggested that the therapeutic efficacy might not be seen in the study period, and incremental response might occur during long-term follow-up. Therefore it is also important to clarify the long-term outcome of treatment in this dually infected population. Evaluation of the long term effects of treatment with peginterferon alfa-2a plus ribavirin for patients with chronic hepatitis C/ hepatitis B co-Infection and chronic hepatitis C in the original study ML17862 is important. This present protocol is thus to assess whether the HCV SVR is sustained and to assess the durability of the HBV virologic and serologic responses or any incremental response during a 5-year follow-up period, including six months after end of the therapy in the original study and an additional 4 and half years in this project (5 years overall follow-up after the end of treatment). Specifically, we wish to assess the (1) sustained virologic response (SVR) of HCV in both populations, (2) incidence of HBsAg loss and HBsAg seroconversion (HBsAg loss and appearance of anti-HBs) in dually infected population, (3) ALT normalization or flare off-treatment during both populations, (4) reductions of HCV RNA from the original baseline levels in the two patient populations, and (5) reduction of serum HBV DNA off-treatment in the dually infected population. **Detailed Description:** Pegylated IFNs (such as PEG-IFN alfa-2a, PEGASYS®) have been shown to possess a superior efficacy and convenience to conventional IFNs, either alone or in combination with RBV in patients with chronic hepatitis C only \[Zeuzem et al, 2000; Heathcote et al, 2000; Fried et al, 2002; Hadziyannis et al, EASL 2002\]. For patients with chronic hepatitis B, pilot study also revealed that the biochemical and virologic responses were better in HBeAg-positive patients receiving pegylated IFN than those receiving conventional IFN \[24-week post-treatment combined virologic, HBeAg loss, and ALT normalization rate: 28% vs. 12%; Lai et al, APSAL 2002\]. The efficacy using a 24-week combination therapy in the sustained clearance of serum HCV RNA is equivalent to that using a 48-week combination therapy in patients with HCV genotype non-1 \[Hadziyannis et al, EASL 2002\]. A 48-week course of pegylated IFN and RBV combination therapy, in contrast, has been shown to yield a better efficacy in the sustained clearance of serum HCV RNA in patients with HCV genotype 1 than a 24-week combination therapy in western countries \[SVR: 40\~51% vs. 29\~41%, Table 1, Hadziyannis et al, EASL 2002; Poynard et al, 1998\]. Based on these findings, NIH Consensus Statement suggests that patients with genotype 1 need 48 weeks of combination treatment and standard doses of RBV \[NIH 2002\]. Previous study revealed that a 12-week RBV therapy was not effective for patients with chronic hepatitis B \[Kakumu et al, 1993\]. Therefore, in this proposal, the treatment duration will be 24 weeks for HCV genotype 2/3, and will be 48 weeks for HCV genotype 1, in patients with monoinfected chronic hepatitis C and dual chronic hepatitis C and B. Increased RBV dosage has been considered as a contributory factor to the better efficacy in some previous studies. Recent studies suggested that using RBV 800 mg daily is adequate to treatment HCV genotype non-1 but standard dosage of RBV is required to treatment HCV genotype 1 \[NIH 2002\]. We follow the recommendations and use RBV 800 mg daily for HCV genotype non-1, both in dually infected patients and in monoinfected chronic hepatitis C patients. RBV with 1000-1200 mg daily will be used for HCV genotype 1 according the body weight of the patient, both in dually infected patients and in monoinfected chronic hepatitis C patients. Previous studies suggested that chronic hepatitis C may relapse in simple chronic hepatitis C patients who initially obtained sustained virologic responses at 6 months after end of the treatment \[Chemello et al, 1996; Marcellin et al, 1997\]. Although the HCV SVR could be maintained in around 90%, the remaining 10% of these patients may develop hepatitis C relapse during follow-up. Chemello et al followed up 107 patients with chronic hepatitis C who maintained normal aminotransferase levels as long as 12 months after interferon-alpha therapy \[Chemello et al, 1996\]. Hepatitis C virus RNA was detected in 27 (25%) patients with sustained biochemical response; 80 (75%) patients were negative for HCV RNA. Patients positive for HCV RNA were older (P \< 0.001), had received a smaller interferon-alpha dose (P = 0.02), and were more frequently infected with HCV genotype 2 (P \< 0.01). Liver histologic findings were active in 57% of patients positive for HCV RNA, despite normal alanine aminotransferase levels, compared with only 12% of patients who were negative for HCV RNA (P = 0.01). The estimated probability of hepatitis relapse by 4 years after therapy was 53% in viremic patients and 0% in patients negative for HCV RNA (P \< 0.001). Marcellin et al followed up 80 patients who had chronic hepatitis C and received interferon-alpha therapy \[Marcellin et al, 1997\]. The 80 patients had follow-up 1 to 7.6 years (mean +/- SD, 4.0 +/- 2.0 years) after interferon-alpha treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon-alpha treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested. They thus concluded that in patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, long-term sustained biochemical and virologic response is generally seen. Similar finding was noted in one reported case with dual chronic hepatitis B and C \[Yalcin et al, 2003\]. To be noted, this dually infected patient had reactivation of hepatitis B accompanied by severe flare of hepatitis activity during treatment and had relapse of hepatitis C after end of the treatment. Therefore, it is important to follow up the long-term of these patients with dual chronic hepatitis B and C. From another aspect, for the treatment of chronic hepatitis B, the virologic and serologic responses may also not be durable \[Liaw et al, 2005; Lok et al, 2004; Hadziyannis et al, 2003; Janssen et al, 2005\]. Alternatively, previous studies suggested that the therapeutic efficacy might not be seen in the study period, and incremental response might occur during long-term follow-up as learned from previous experiences of using antiviral agents including interferon for the treatment of chronic hepatitis B \[Saruc et al, 2003; Carreno et al, 2001\]. Therefore it is also important to clarify the long-term outcome of treatment in this dually infected population. This present protocol is thus to assess whether the HCV SVR is sustained and to assess the durability of the HBV virologic and serologic responses or any incremental response during a 5-year follow-up period, including six months after end of the therapy in the original study and an additional 4 and half years in this project (5 years overall follow-up after the end of treatment). Specifically, we wish to assess the (1) sustained virologic response (SVR) of HCV in both populations, (2) incidence of HBsAg loss and HBsAg seroconversion (HBsAg loss and appearance of anti-HBs) in dually infected population, (3) ALT normalization or flare off-treatment during both populations, (4) reductions of HCV RNA from the original baseline levels in the two patient populations, and (5) reduction of serum HBV DNA off-treatment in the dually infected population. ### Conditions Module **Conditions:** - Coinfection With Hepatitis B Virus and Hepatitis C Virus - Monoinfection With Hepatitis C Virus **Keywords:** - Observation - Post-treatment ### Design Module #### Design Info **Observational Model:** DEFINED_POPULATION **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 320 **Study Type:** OBSERVATIONAL ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients who were randomized, treated and returned for follow up in the ML17862 protocol will be eligible for inclusion in this protocol Exclusion Criteria: * Patients unwilling to provide informed consent or abide by the requirements of the study. * Patients who have already initiated anti-HCV or HBV treatment, approved or investigational since completion of the original protocol **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Taipei city **Country:** China **Facility:** Pei-Jer Chen **State:** Taiwan **Zip:** 100 #### Overall Officials **Official 1:** **Affiliation:** National Taiwan University Hospital **Name:** Pei-Jer Chen, M.D.; Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Liu CJ, Chuang WL, Lee CM, Yu ML, Lu SN, Wu SS, Liao LY, Chen CL, Kuo HT, Chao YC, Tung SY, Yang SS, Kao JH, Liu CH, Su WW, Lin CL, Jeng YM, Chen PJ, Chen DS. Peginterferon alfa-2a plus ribavirin for the treatment of dual chronic infection with hepatitis B and C viruses. Gastroenterology. 2009 Feb;136(2):496-504.e3. doi: 10.1053/j.gastro.2008.10.049. Epub 2008 Oct 29. **PMID:** 19084016 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007239 - Term: Infections - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000006525 - Term: Hepatitis, Viral, Human - ID: D000014777 - Term: Virus Diseases - ID: D000004769 - Term: Enterovirus Infections - ID: D000010850 - Term: Picornaviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000086982 - Term: Blood-Borne Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000018178 - Term: Flaviviridae Infections - ID: D000018347 - Term: Hepadnaviridae Infections - ID: D000004266 - Term: DNA Virus Infections - ID: D000002908 - Term: Chronic Disease - 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 - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: Rare - Name: Rare 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: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9595 - Name: Hepatitis B - Relevance: HIGH - As Found: Hepatitis B - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M9607 - Name: Hepatitis, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M21613 - Name: Hepatitis C, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis C - ID: M29581 - Name: Coinfection - Relevance: HIGH - As Found: Co-infection - 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: 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: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M20324 - Name: Flaviviridae Infections - Relevance: LOW - As Found: Unknown - ID: M20487 - Name: Hepadnaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M7442 - Name: DNA Virus Infections - 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 - ID: T2787 - Name: Herpes Simiae (B Virus) - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006506 - Term: Hepatitis A - ID: D000006526 - Term: Hepatitis C - ID: D000006509 - Term: Hepatitis B - ID: D000019698 - Term: Hepatitis C, Chronic - ID: D000060085 - Term: Coinfection - ID: D000006505 - Term: Hepatitis - ID: D000006521 - Term: Hepatitis, Chronic ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M15083 - Name: Ribavirin - Relevance: LOW - As Found: Unknown - ID: M247369 - Name: Peginterferon alfa-2a - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04103879 **Brief Title:** US Study of UM171-Expanded CB in Patients With High Risk Leukemia/Myelodysplasia **Official Title:** A Phase II Open-Label Study of UM171-Expanded Cord Blood Transplantation in Patients With High and Very High Risk Acute Leukemia/Myelodysplasia #### Organization Study ID Info **ID:** ECT-001-CB.004 #### Organization **Class:** INDUSTRY **Full Name:** ExCellThera inc. #### Secondary ID Infos **Domain:** FHCRC **ID:** Study 8743 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2026-02 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-20 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-15 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2026-02 **Type:** ESTIMATED #### Start Date **Date:** 2020-11-13 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2019-09-26 **Type:** ACTUAL **Study First Submit Date:** 2019-09-23 **Study First Submit QC Date:** 2019-09-24 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Fred Hutchinson Cancer Center #### Lead Sponsor **Class:** INDUSTRY **Name:** ExCellThera 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:** Cord blood (CB) transplants are an option for patients lacking an HLA identical donor but are hampered by low cell dose, prolonged aplasia and high transplant related mortality. UM171, a novel and potent agonist of hematopoietic stem cell self renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. In a previous trial (NCT02668315), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe. UM171 expanded CB was associated with a median neutrophil recovery at day (D)+18 post transplant. Amongst 22 patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (5%) and grade 3-4 acute GVHD (10%) were low. There was no moderate-severe chronic GVHD. Thus, overall and progression free survival at 12 months were impressive at 90% and 74%, respectively. The UM171 expansion protocol allowed access to smaller, better HLA matched CBs as \>80% of patients received a 6-7/8 HLA matched CB. Interestingly there were patients with high-risk hematologic malignancies and multiple comorbidities (5 patients who had already failed an allogeneic transplant and 5 patients with refractory/relapsed acute leukemia/aggressive lymphoma). Despite this high risk population, progression was 20% at 12 months. This new study seeks to test a similar strategy in a group of patients with high risk acute leukemia/myelodysplasia. ### Conditions Module **Conditions:** - High Risk Hematological Malignancy - Cord Blood Transplant ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will receive a myeloablative conditioning regimen. The cord to be expanded will undergo CD34+ selection. The CD34- product is cryopreserved and will be thawed and infused on Day +1 post-transplant. The CD34+ product will be placed in a closed culture with UM171 for a 7-day expansion and is infused on Day 0. Patients will receive standard supportive care and GVHD prophylaxis (such as MMF and tacrolimus). **Intervention Names:** - Biological: ECT-001-CB (UM171-Expanded Cord Blood Transplant) **Label:** ECT-001-Expanded CB **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - ECT-001-Expanded CB **Description:** Conditioning: High dose TBI (1320 cGy TBI + Fludarabine 75 mg/m2 + Cyclophosphamide 120 mg/kg) or Intermediate Intensity regimen (400 cGy TBI + Fludarabine 150 mg/m2 + Cyclophosphamide 50 mg/kg + Thiotepa 10 mg/kg). Single UM171-Expanded CB transplant (CD34+: 2.5-50x10E5/kg, CD3+\>1x10E6/kg) Immunosuppression: Tacrolimus/MMF **Name:** ECT-001-CB (UM171-Expanded Cord Blood Transplant) **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0) **Measure:** Adverse events of ECT-001-CB **Time Frame:** 100 days post-transplant **Description:** All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0) **Measure:** Adverse events of ECT-001-CB **Time Frame:** 2 years post-transplant **Description:** RFS will be measured from time of transplant until disease relapse, death or last follow-up **Measure:** Relapse-free survival **Time Frame:** At 1-year post-transplant **Description:** RFS will be measured from time of transplant until disease relapse, death or last follow-up **Measure:** Relapse-free survival **Time Frame:** At 2-year post-transplant #### Secondary Outcomes **Description:** Neutrophil engraftment (the first day of attainment of an absolute neutrophil count ≥0.5 x 10E9/L for 3 consecutive days. Time to ANC ≥ 0.1 x 10E9/L will also be documented) and platelet engraftment (first day of a sustained platelet count ≥ 20 x 10E9/L with no platelet transfusion in the preceding 7 days) **Measure:** Time to Neutrophil and Platelet engraftment **Time Frame:** First 60 days **Description:** TRM is defined as any death of any cause other than malignant relapse, occurring after the commencement of conditioning regimen that could be related to the transplantation procedure **Measure:** Incidence of transplant related mortality **Time Frame:** At day 100 post-transplant **Description:** TRM is defined as any death of any cause other than malignant relapse, occurring after the commencement of conditioning regimen that could be related to the transplantation procedure **Measure:** Incidence of transplant related mortality **Time Frame:** At 1-year post-transplant **Description:** Acute and chronic GVHD by NIH criteria **Measure:** Incidence of GVHD **Time Frame:** At 2 years post-transplant **Description:** Any of infections requiring systemic therapy, e.g., invasive candidiasis, aspergillus, other invasive fungi, CMV, adenovirus, EBV, HHV-6, HSV, VZV, PCP, toxoplasmosis and mycobacterium **Measure:** Incidence of grade 3 or higher infectious complications **Time Frame:** At 2 years post-transplant **Measure:** Incidence of pre-engraftment/engraftment syndrome requiring therapy **Time Frame:** At 2 years post-transplant **Description:** GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up **Measure:** GRFS and CRFS **Time Frame:** At 1-year post-transplant **Description:** GRFS and CRFS will be measured from time of transplant until disease relapse, death or last follow-up **Measure:** GRFS and CRFS **Time Frame:** At 2-year post-transplant ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. High and very high-risk hematologic malignancy defined as: 1. Acute Myeloid Leukemia (Primary induction failure, Chemorefractory relapse, Relapse after allogeneic or autologous transplant, High risk AML in CR1, ≥ CR2) 2. Acute Lymphoid leukemia (Primary induction failure, High risk ALL in CR1, ≥ CR2, Chemorefractory relapse, Relapse after allogeneic or autologous transplant) 3. Myelodysplastic syndrome (Relapse after allogeneic or autologous transplant, ≥10% blasts within 30 days of start of conditioning regimen, Poor and very poor cytogenetics abnormalities, CMML with HCT-specific CPSS score high or intermediate-2, Stable disease, Progressive disease while on azacitidine). 4. Chronic myelogenous leukemia (Patients who progressed to blast crisis) 2. Availability of 2 CBs ≥ 4/6 HLA match with pre-freeze CD34+ cell count ≥0.5 x 10E5/kg and TNC≥1.5 x 10E7/kg 3. Karnofsky ≥70. 4. LVE fraction ≥ 40% or fractional shortening \>22% 5. FVC, FEV1 and DLCOc ≥ 50% of predicted 6. Bilirubin \< 2 x ULN; AST and ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN. 7. Creatinine \< 2.0 mg/dl. 8. HCT-CI ≤3 if patients have ≥5% blasts in the bone marrow and HCT-CI ≤5 if 60-65 years old. Exclusion Criteria: 1. Allogeneic myeloablative transplant within 6 months. 2. Autologous hematopoietic stem cell transplant within 6 months. 3. Active or recent invasive fungal infection. 4. Presence of a malignancy other than the one for which the UCB transplant is being performed and the expected survival related to the malignancy is estimated to be less than 75% at 5 years. 5. HIV positivity. 6. Hepatitis B or C infection with measurable viral load. 7. Liver cirrhosis. 8. Pregnancy, breastfeeding or unwillingness to use appropriate contraception. 9. Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome. 10. Active central nervous system involvement. 11. Chloroma \> 2 cm. **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Aurora **Country:** United States **Facility:** University of Colorado School of Medicine. Anschutz Medical Campus **State:** Colorado **Zip:** 80045 **Location 2:** **City:** Seattle **Country:** United States **Facility:** Fred Hutchinson / University of Washington Cancer Consortium **State:** Washington **Zip:** 98109 **Location 3:** **City:** Rotterdam **Country:** Netherlands **Facility:** Erasmus Medical Center **State:** GD **Zip:** 3015 ### IPD Sharing Statement Module **Info Types:** - CSR **IPD Sharing:** YES ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000006402 - Term: Hematologic Diseases - ID: D000009371 - Term: Neoplasms by Site - ID: D000001855 - Term: Bone Marrow Diseases - ID: D000011230 - Term: Precancerous Conditions ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: LOW - As Found: Unknown - ID: M21314 - Name: Hematologic Neoplasms - Relevance: HIGH - As Found: Hematological Malignancies - ID: M14164 - Name: Preleukemia - Relevance: HIGH - As Found: Myelodysplasia - ID: M12145 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplasia - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M5134 - Name: Bone Marrow Diseases - Relevance: LOW - As Found: Unknown - ID: M14111 - Name: Precancerous Conditions - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T3993 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplasia ### Condition Browse Module - Meshes - ID: D000019337 - Term: Hematologic Neoplasms - ID: D000011289 - Term: Preleukemia - ID: D000009190 - Term: Myelodysplastic Syndromes ### 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: LOW - As Found: Unknown - ID: M283230 - Name: Fludarabine - Relevance: LOW - As Found: Unknown - ID: M18950 - Name: Tacrolimus - Relevance: LOW - As Found: Unknown - ID: M16615 - Name: Thiotepa - Relevance: LOW - As Found: Unknown - ID: M225513 - Name: Fludarabine phosphate - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01325779 **Brief Title:** Comparison of Subcutaneous Heparin and Enoxaparin for Deep Venous Thrombosis (DVT) Prophylaxis in Surgical Intensive Care Patients **Official Title:** Prevention of Lower Extremity Deep Venous Thrombosis in the Surgical Intensive Care Unit: a Randomized Trial Comparing Subcutaneous Heparin and Subcutaneous Enoxaparin #### Organization Study ID Info **ID:** HIC 2010-113 #### Organization **Class:** OTHER **Full Name:** William Beaumont Hospitals ### Status Module #### Completion Date **Date:** 2013-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-05-20 **Type:** ESTIMATED **Last Update Submit Date:** 2013-05-17 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2013-02 **Type:** ACTUAL #### Start Date **Date:** 2011-03 **Status Verified Date:** 2013-05 #### Study First Post Date **Date:** 2011-03-30 **Type:** ESTIMATED **Study First Submit Date:** 2011-03-28 **Study First Submit QC Date:** 2011-03-29 **Why Stopped:** poor enrollment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Lisa Louwers #### Responsible Party **Investigator Affiliation:** William Beaumont Hospitals **Investigator Full Name:** Lisa Louwers **Investigator Title:** Principal Investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Study hypothesis: Subcutaneous enoxaparin is more effective than subcutaneous heparin in preventing the development of DVT in the general surgical intensive care unit population. Hospitalized patients are at increased risk for the development of blood clots in the legs, known as deep venous thrombosis (DVT). Surgical patients are in a higher risk category than the general hospital population due to a number of factors including undergoing surgery and increased risk of immobility. The highest risk patients are in the surgical intensive care unit, where their surgical risks for blood clots are combined with issues such as sepsis, acquired blood clotting disorders, and increasing age, each of which are factors that contribute to the risk of blood clot development. 1. Patients who develop these blood clots (DVTs) are at risk for chronic leg swelling, pain, and in some cases, chronic ulcer development on the leg. In the worst case scenario, these blood clots can break away and migrate to the lungs where they cause a pulmonary embolism (PE), a clot in the lungs that can cause significant breathing difficulty requiring intubation and mechanical ventilation, and in some cases, death. According to recent research, DVTs account for over 200,000 patient deaths each year nationwide. 2. A large amount of data has supported the use of medication called heparin or enoxaparin in low doses to prevent these blood clots from forming while in the hospital. Both of these medications are considered standard of care for use patients considered moderate and high risk for the development of DVT. 3. While both of these medications have been shown to significantly reduce the occurrence of DVT in appropriate doses, 4. there has never been a direct comparison of the two medications in the highest-risk population of the surgical intensive care unit. Our own preliminary data suggests patients may have a lower incidence of DVTs with the use of enoxaparin versus heparin. Part of the reason for this may be the requirement for three times daily dosing of the heparin compared to once daily dosing for enoxaparin. There may also be some inherent differences in the efficacy of the medications themselves. ### Conditions Module **Conditions:** - Lower Extremity Deep Venous Thrombosis **Keywords:** - deep venous thrombosis - DVT - enoxaparin - heparin - surgical intensive care ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: heparin **Label:** subcutaneous heparin **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Intervention Names:** - Drug: enoxaparin **Label:** subcutaneous enoxaparin **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - subcutaneous heparin **Description:** subcutaneous heparin 5000 units every 8 hours **Name:** heparin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - subcutaneous enoxaparin **Description:** subcutaneous enoxaparin 40 milligrams every 24 hours **Name:** enoxaparin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Development of lower extremity deep venous thrombosis **Time Frame:** hospital admission (day 1 ) to 3 months post discharge #### Secondary Outcomes **Measure:** Adverse events associated with use of subcutaneous heparin and enoxaparin **Time Frame:** hospital admission (day 1) through discharge ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * age \> 18 years old * admission to the surgical intensive care unit * admitting physician is a surgeon or patient is status-post a surgical procedure Exclusion Criteria: * age \< 18 years old * inability to obtain informed consent from patient or legal representative within 24 hours of SICU admission * patient admitted to neurosurgery or status-post a neurosurgical procedure * patient status-post an orthopedic procedure * patient admitted with a primary diagnosis of trauma * patient with a history of a bleeding disorder or other contraindication to even low-dose anticoagulation medicine including a history of heparin-induced thrombocytopenia verified with a positive serotonin-release assay or have a high clinical suspicion of new onset heparin-induced thrombocytopenia resulting in the discontinuation of heparin or enoxaparin by the treating physicians * patients on current full anticoagulation medications including a heparin drip or warfarin **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Royal Oak **Country:** United States **Facility:** William Beaumont Hospital **State:** Michigan **Zip:** 48073 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000016769 - Term: Embolism and Thrombosis - ID: D000014652 - Term: Vascular 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: M16686 - Name: Thrombosis - Relevance: HIGH - As Found: Thrombosis - ID: M22071 - Name: Venous Thrombosis - Relevance: HIGH - As Found: Venous Thrombosis - ID: M7784 - Name: Embolism - 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 ### Condition Browse Module - Meshes - ID: D000013927 - Term: Thrombosis - ID: D000020246 - Term: Venous Thrombosis ### Intervention Browse Module - Ancestors - ID: D000000925 - Term: Anticoagulants - ID: D000005343 - Term: Fibrinolytic Agents - ID: D000050299 - Term: Fibrin Modulating Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: FiAg - Name: Fibrinolytic Agents - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M9579 - Name: Heparin - Relevance: HIGH - As Found: Obesity - ID: M20152 - Name: Enoxaparin - Relevance: HIGH - As Found: Below - ID: M46053 - Name: Calcium heparin - Relevance: LOW - As Found: Unknown - ID: M137075 - Name: Enoxaparin sodium - Relevance: LOW - As Found: Unknown - ID: M4244 - Name: Anticoagulants - Relevance: LOW - As Found: Unknown - ID: M8473 - Name: Fibrinolytic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000006493 - Term: Heparin - ID: D000017984 - Term: Enoxaparin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03378479 **Acronym:** POSA-FLU **Brief Title:** Posaconazole for the Prevention of Influenza-associated Aspergillosis in Critically Ill Patients **Official Title:** A Phase iv, Interventional, Non-blinded, Randomized Controlled Multicenter Study of Posaconazole Prophylaxis for the Prevention of Influenza-associated Aspergillosis (IAA) in Critically Ill Patients #### Organization Study ID Info **ID:** POSA-FLU #### Organization **Class:** OTHER **Full Name:** Universitaire Ziekenhuizen KU Leuven ### Status Module #### Completion Date **Date:** 2021-03-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-06-30 **Type:** ACTUAL **Last Update Submit Date:** 2022-06-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-03-31 **Type:** ACTUAL #### Start Date **Date:** 2017-12-27 **Type:** ACTUAL **Status Verified Date:** 2022-06 #### Study First Post Date **Date:** 2017-12-19 **Type:** ACTUAL **Study First Submit Date:** 2017-10-30 **Study First Submit QC Date:** 2017-12-18 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Merck Sharp & Dohme LLC #### Lead Sponsor **Class:** OTHER **Name:** Universitaire Ziekenhuizen KU Leuven #### Responsible Party **Investigator Affiliation:** Universitaire Ziekenhuizen KU Leuven **Investigator Full Name:** Joost Wauters, prof. dr. **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:** False ### Description Module **Brief Summary:** The objective of this study is to deliver proof of concept that antifungal prophylaxis can reduce the incidence of Influenza Associated Aspergillosis (IAA) in ICU (intensive care unit) patients with severe influenza. The investigators will perform an interventional non-blinded randomized controlled multicentric proof-of-concept study in patients with severe influenza admitted to the ICU. Patients will be randomized to the posaconazole prophylaxis group or to the SOC (standard of care) group. Oseltamivir will be started at the discretion of the investigator. Patients in the posaconazole group will receive posaconazole prophylaxis for 7 days. addendum: pharmacokinetics of posaconazole as prophylaxis for invasive fungal disease on ICU **Detailed Description:** Critically ill patients with PCR-confirmed influenza criteria) are eligible for inclusion in this study and will be randomized to or the posaconazole prophylaxis group or the SOC group. If a patient is randomized to the posaconazole prophylaxis group, posaconazole (Noxafil, MSD) will be started intravenously from day 1 of randomization (2\*300mg( milligram) /d on day 1, followed by 1\*300mg/d from day 2 for 7 days) In both patient groups (prophylaxis and SOC) oseltamivir (non-IMP) will be started at the discretion of the treating physician from the first day of ICU admission as 2\*150 mg/day for 10 days. If oseltamivir had already been started up before ICU admission, oseltamivir treatment will be continued up to a total of 10 days. Within 48 hours after influenza diagnosis a bronchoscopy with BAL (bronchoalveolar lavage) and a serum galactomannan will be performed as part of routine ICU care in this type of patients. If an IAA-infection is suspected based on the result of this BAL ((A) Aspergillus cultured from BAL, or (B) a galactomannan (GM)the patient will be withdrawn from the study and antifungal treatment will be started. addendum: Extensive PK sampling (UZ Leuven and Radboud): full PK curve on day 2 and day 5 (predose, 1.5; 2,3,4,6,8,10,12,18,24 h post infusion). on non PK days, until day 7, predose sample. PK in BAL fluid only in patients with mechanical ventilation and when medically indicated. Limited PK sampling: on day 2 and day 5: 1.5-3h, 4-8 h;8-12h; 12-24h post dose. on non PK days: PK pre dose. ### Conditions Module **Conditions:** - Aspergillosis; Pulmonary, Invasive (Etiology) **Keywords:** - Influenza ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 88 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** standard of care (SOC) treatment for influenza pneumonia +posaconazole 2\*300mg/d IV on day 1, followed by 1\*300mg/d IV from day 2 for 7 days; vials containing 18mg posaconazole /mL, 300mg posaconazole/vial in total) **Intervention Names:** - Drug: SOC +Posaconazole 18 MG/ML (milligram/milliliter) - Other: standard of care (SOC) **Label:** SOC + 'Posaconazole 18 MG/ML' **Type:** OTHER #### Arm Group 2 **Description:** standard of care treatment for influenza pneumonia (at the investigators discretion) **Intervention Names:** - Other: standard of care (SOC) **Label:** Standard of Care **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - SOC + 'Posaconazole 18 MG/ML' **Description:** .2\*300mg/d IV on day 1, followed by 1\*300mg/d IV from day 2 for 7 days (total 7 days) **Name:** SOC +Posaconazole 18 MG/ML (milligram/milliliter) **Other Names:** - Noxafil **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - SOC + 'Posaconazole 18 MG/ML' - Standard of Care **Description:** treatment for influenza pneumonia at the investigators discretion **Name:** standard of care (SOC) **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** A patient with IAA-infection is defined as a patient having mycological evidence of Aspergillus and at least one Aspergillus compatible sign or symptom and radiological abnormalities **Measure:** The incidence of IAA-infection at ICU discharge **Time Frame:** from date of admission in ICU assessed up to ICU discharge, approximately 21 days #### Secondary Outcomes **Description:** days to IAA diagnosis **Measure:** Time to IAA diagnosis **Time Frame:** from date of inclusion to date of first sign/symptom of IAA infection, assessed up to ICU discharge, approximately 10 days **Description:** amount of days at ICU **Measure:** length of ICU stay **Time Frame:** from date of admission in ICU to date of discharge from ICU, approximately 20 days **Description:** admission days **Measure:** length of hospital stay **Time Frame:** from date of admission in hospital to date of discharge from hospital, approximately 25 days **Description:** survival status **Measure:** mortality **Time Frame:** at day 30 and at day 90 **Description:** altered clearance of posaconazole in critically ill patients **Measure:** identify changes in PK of posaconazole in critically ill patients **Time Frame:** from day 1 until day 7 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Written informed consent must be obtained from the patient or his/her legal representative prior to any study procedures 2. Adult patient (≥ 18 years) 3. PCR-confirmed influenza based on nasopharyngeal swab (NS), bronchial aspirate (BA) or broncho-alveolar lavage (BAL) within 7 days before ICU admission or within 48 hours after ICU admission. If PCR is not available a positive result of a rapid test is required (a negative rapid test does not imply absence of influenza and thus requires confirmation by PCR) 4. Influenza symptoms present for no more than 10 days before ICU admission 5. Respiratory distress as the main reason for ICU admission. Respiratory distress will be defined as tachypnea with an respiratory rate ≥ 25x/min and a paO2/fiO2-ratio (fraction of inspired oxygen) ≤ 300 with or without (bilateral) infiltrates. Exclusion Criteria: 1. Patients with age \< 18 years 2. Pregnant women (based on a positive serum sample) 3. Expected survival on ICU admission ≤ 48h 4. Patients having influenza symptoms for more than 10 days before ICU admission 5. Patients being transferred from another hospital ward or another hospital who already have mycological evidence for an IAA-infection (based on sputum, BA or BAL culture, BAL or serum GM) 6. Patients with known intolerance or hypersensitivity to posaconazole or other azole antifungal agents 7. Patients that are being treated actively with antifungal agents for invasive aspergillosis 8. Patients with a QTc (corrected QT interval) interval ≥500 msec 9. Patients with liver cirrhosis (Child C) 10. Participation in another interventional clinical trial - **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Brugge **Country:** Belgium **Facility:** AZ Sint Jan **Zip:** 8000 **Location 2:** **City:** Gent **Country:** Belgium **Facility:** UZ Gent **Zip:** 9000 **Location 3:** **City:** Leuven **Country:** Belgium **Facility:** UZ Leuven **Zip:** 3000 **Location 4:** **City:** Roeselare **Country:** Belgium **Facility:** AZ Delta **Zip:** 8800 **Location 5:** **City:** Groningen **Country:** Netherlands **Facility:** Universitair Medisch Centrum **Location 6:** **City:** Nijmegen **Country:** Netherlands **Facility:** UMC Radboud **Zip:** 6500 **Location 7:** **City:** Rotterdam **Country:** Netherlands **Facility:** MC Erasmus **Zip:** 3015 #### Overall Officials **Official 1:** **Affiliation:** UZ Leuven **Name:** Joost Wauters, Phd **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Radboud University Medical Center **Name:** Paul Verweij, Phd **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Vanderbeke L, Janssen NAF, Bergmans DCJJ, Bourgeois M, Buil JB, Debaveye Y, Depuydt P, Feys S, Hermans G, Hoiting O, van der Hoven B, Jacobs C, Lagrou K, Lemiale V, Lormans P, Maertens J, Meersseman P, Megarbane B, Nseir S, van Oers JAH, Reynders M, Rijnders BJA, Schouten JA, Spriet I, Thevissen K, Thille AW, Van Daele R, van de Veerdonk FL, Verweij PE, Wilmer A, Bruggemann RJM, Wauters J; Dutch-Belgian Mycosis Study Group. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial. Intensive Care Med. 2021 Jun;47(6):674-686. doi: 10.1007/s00134-021-06431-0. Epub 2021 May 29. **PMID:** 34050768 ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2022-06-30 - Date Unknown: Unknown #### Event: RESET - Date: 2023-04-28 - Date Unknown: Unknown ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000009976 - Term: Orthomyxoviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000009181 - Term: Mycoses - ID: D000001423 - Term: Bacterial Infections and Mycoses ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M19010 - Name: Critical Illness - Relevance: LOW - As Found: Unknown - ID: M10295 - Name: Influenza, Human - Relevance: HIGH - As Found: Influenza - ID: M4535 - Name: Aspergillosis - Relevance: HIGH - As Found: Aspergillosis - 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: M12902 - Name: Orthomyxoviridae 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: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M12136 - Name: Mycoses - Relevance: LOW - As Found: Unknown - ID: M4722 - Name: Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: T511 - Name: Aspergillosis - Relevance: HIGH - As Found: Aspergillosis ### Condition Browse Module - Meshes - ID: D000007251 - Term: Influenza, Human - ID: D000001228 - Term: Aspergillosis ### Intervention Browse Module - Ancestors - ID: D000000935 - Term: Antifungal Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000014344 - Term: Trypanocidal Agents - ID: D000000981 - Term: Antiprotozoal Agents - ID: D000000977 - Term: Antiparasitic Agents - ID: D000058888 - Term: 14-alpha Demethylase Inhibitors - ID: D000065607 - Term: Cytochrome P-450 Enzyme Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000065088 - Term: Steroid Synthesis Inhibitors - ID: D000006727 - Term: Hormone Antagonists - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M219015 - Name: Posaconazole - Relevance: HIGH - As Found: Venous Thromboembolism - ID: M6252 - Name: Clotrimazole - Relevance: LOW - As Found: Unknown - ID: M11796 - Name: Miconazole - Relevance: LOW - As Found: Unknown - ID: M4254 - Name: Antifungal Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M4298 - Name: Antiprotozoal Agents - Relevance: LOW - As Found: Unknown - ID: M4294 - Name: Antiparasitic Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M30537 - Name: Cytochrome P-450 Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000101425 - Term: Posaconazole ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2022-06-30 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2022-06-30 - Reset Date: 2023-04-28 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04395079 **Brief Title:** Brachytherapy With Durvalumab or Tremelimumab for the Treatment of Patients With Platinum-Resistant, Refractory, Recurrent, or Metastatic Gynecological Malignancies **Official Title:** Brachytherapy With Durvalumab (MEDI4736) and Tremelimumab in Subjects With Platinum-Resistant or Refractory and Recurrent or Metastatic Gynecological Malignancies #### Organization Study ID Info **ID:** 19-000459 #### Organization **Class:** OTHER **Full Name:** Jonsson Comprehensive Cancer Center #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2020-01095 **Type:** REGISTRY **Domain:** UCLA / Jonsson Comprehensive Cancer Center **ID:** 19-000459 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2025-06-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-15 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-13 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-06-01 **Type:** ESTIMATED #### Start Date **Date:** 2020-08-07 **Type:** ACTUAL **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2020-05-20 **Type:** ACTUAL **Study First Submit Date:** 2020-05-08 **Study First Submit QC Date:** 2020-05-14 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** AstraZeneca #### Lead Sponsor **Class:** OTHER **Name:** Jonsson Comprehensive Cancer Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This phase II trial studies the side effects and how well brachytherapy with durvalumab or tremelimumab work for the treatment of gynecological malignancies that is resistant to platinum therapy (platinum-resistant), does not respond to treatment (refractory), has come back (recurrent), or has spread to other places in body (metastatic). Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial is being done to see whether brachytherapy with durvalumab or tremelimumab works better in treating patients with gynecological malignancies. **Detailed Description:** PRIMARY OBJECTIVES: I. To determine the safety of the treatment combination consisting of brachytherapy and tremelimumab. (Safety lead-in) II. To determine the median progression-free survival with brachytherapy and checkpoint inhibition with either durvalumab or tremelimumab. (Dose expansion) SECONDARY OBJECTIVES: I. To estimate the efficacy of brachytherapy and durvalumab or brachytherapy and tremelimumab in terms of: Ia. Local control of the irradiated tumor. Ib. Overall response rate. Ic. Response at non-irradiated lesions in subjects with multiple sites of disease subjects. Id. Duration of response. Ie. Disease specific survival. If. Overall survival. II. To further determine the safety and tolerability of brachytherapy with durvalumab and brachytherapy with tremelimumab (expansion cohorts). EXPLORATORY OBJECTIVE: I. To explore the immunologic changes associated with the combination of brachytherapy with durvalumab and brachytherapy with tremelimumab. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive durvalumab intravenously (IV) on day 1. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo brachytherapy on day 8. Treatment repeats every 21 days for 3 fractions in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive tremelimumab IV on day 1. Treatment repeats every 28 days for 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo brachytherapy on day 8. Treatment repeats every 21 days for 3 fractions in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks. ### Conditions Module **Conditions:** - Metastatic Malignant Female Reproductive System Neoplasm - Platinum-Resistant Malignant Female Reproductive System Neoplasm - Recurrent Malignant Female Reproductive System Neoplasm - Refractory Malignant Female Reproductive System Neoplasm ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 9 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receive durvalumab IV on day 1. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo brachytherapy on day 8. Treatment repeats every 21 days for 3 fractions in the absence of disease progression or unacceptable toxicity. **Intervention Names:** - Biological: Durvalumab - Radiation: Internal Radiation Therapy **Label:** Arm I (durvalumab, brachytherapy) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients receive tremelimumab IV on day 1. Treatment repeats every 28 days for 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo brachytherapy on day 8. Treatment repeats every 21 days for 3 fractions in the absence of disease progression or unacceptable toxicity. **Intervention Names:** - Radiation: Internal Radiation Therapy - Biological: Tremelimumab **Label:** Arm II (tremelimumab, brachytherapy) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm I (durvalumab, brachytherapy) **Description:** Given IV **Name:** Durvalumab **Other Names:** - Imfinzi - Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer - MEDI-4736 - MEDI4736 **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Arm I (durvalumab, brachytherapy) - Arm II (tremelimumab, brachytherapy) **Description:** Undergo brachytherapy **Name:** Internal Radiation Therapy **Other Names:** - Brachytherapy - Brachytherapy, NOS - Internal Radiation - Internal Radiation Brachytherapy - Radiation Brachytherapy - Radiation, Internal **Type:** RADIATION #### Intervention 3 **Arm Group Labels:** - Arm II (tremelimumab, brachytherapy) **Description:** Given IV **Name:** Tremelimumab **Other Names:** - Anti-CTLA4 Human Monoclonal Antibody CP-675,206 - CP-675 - CP-675,206 - CP-675206 - Ticilimumab **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Toxicity will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 criteria. **Measure:** Incidence of adverse events (safety lead-in) **Time Frame:** Up to 90 days **Description:** PFS will be estimated in each study arm by Kaplan-Meier estimate, where PFS is a composite endpoint based on radiologic progression, clinical deterioration or death. Furthermore, log rank test will be used to test if there is significant difference in PFS between two arms. In addition, PFS will be also estimated for localized subjects and metastatic subjects separately within each arm and stratified log rank test will be used as well. **Measure:** Progression free survival (PFS) (dose expansion) **Time Frame:** From the first day of the treatment to the first occurrence of disease progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 or death, assessed up to 2 years #### Secondary Outcomes **Description:** Will be determined by RECIST v 1.1 from the date of randomization to the date of first local progression. **Measure:** Local control at the irradiated site **Time Frame:** Up to 2 years **Description:** ORR will be as determined by RECIST v 1.1. The ORR will be defined as the number (%) of subjects with at least 1 visit response of complete response (CR) or partial response (PR). Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR. Subjects who go off treatment without progression receive a subsequent therapy, and then responds will not be included as responders in the ORR. The overall response rate will also be compared between treatment groups. **Measure:** Overall response rate (ORR) **Time Frame:** Up to 2 years **Description:** As determined by RECIST v 1.1 with response (PR and CR) sites away from the primary irradiated tumor. **Measure:** Response at non-irradiated lesions in subjects with multiple sites of disease **Time Frame:** Up to 2 years **Description:** Will be defined as the time from the date of the first documented response until the first date of documented progression or death. The end of response should coincide with the date of progression or death from any cause used for the RECIST 1.1 PFS endpoint. The time of initial response will be defined as the latest of dates contributing towards the first visit response of CR or PR. If a subject does not progress following a response, then their DoR will be censored at the PFS censoring time. DoR will not be defined for those subjects who do not have a documented response. **Measure:** Duration of response (DoR) **Time Frame:** Up to 2 years **Measure:** Disease-specific survival **Time Frame:** From the first day of treatment to the date of death related to treatment and/or disease, assessed up to 2 years **Measure:** Overall survival **Time Frame:** From the first day of treatment to the date of death due to any cause as determined, assessed up to 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects with platinum-resistant or refractory, recurrent or metastatic gynecological malignancies, including ovarian, endometrial, or cervical cancer are eligible for enrollment. Subjects unsuitable or refusing platinum-based chemotherapy are allowed to enrolled * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria. Thus, subjects with metastatic disease must have at least 1 lesion, not previously irradiated, that can be accurately measured at baseline as \>=10 mm in the longest diameter (except lymph nodes which must have a short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurement as per RECIST v1.1 guidelines * Disease amenable to be treated safely with brachytherapy * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy of \>= 12 weeks * Subjects must consent to provide an archived tumor specimen from within 12 months prior to study entry (ie, from subject signing consent to participate in the study). If not available, subjects should have at least 1 lesion amenable to biopsy and consent to provide a pre-treatment fresh biopsy. Additional archival tissue from beyond 12 months prior to study entry is also requested, if available, to support exploratory analyses * Hemoglobin \>= 9.0 g/dL * Absolute neutrophil count (ANC) \>= 1.5 (or 1.0) x (\>= 1500 per mm\^3) * Platelet count \>= 100 (or 75) x 10\^9/L (\>= 75,000 per mm\^3) * Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN) * This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =\< 5 x ULN * Creatinine \< 3 x upper limit of normal * Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply * Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) * Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) * Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up Exclusion Criteria: * Prior use of checkpoint inhibitors * Prior radiation in which the 50% isodose line overlaps with intended site for brachytherapy * Radiation treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug * Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater * Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) * Participation in another clinical study with an investigational therapeutic pharmaceutical agent i.e. chemotherapy, targeted therapy, or immunotherapy =\< 21 days or =\< 5 half-lives * Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study * Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) =\< 21 days or 5 half-lives prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or pharmacokinetics (PK) properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator * Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade \>= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria * Subjects with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician * Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study physician * Any concurrent chemotherapy, investigation product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable * Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable * History of allogenic organ transplantation * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion: * Subjects with vitiligo or alopecia * Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Subjects without active disease in the last 5 years may be included but only after consultation with the study physician * Subjects with celiac disease controlled by diet alone * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the subject to give written informed consent * History of another primary malignancy except for: * Malignancy treated with curative intent and with no known active disease \>= 5 years before the first dose of IP and of low potential risk for recurrence * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease * History of leptomeningeal carcinomatosis * Brain metastases or spinal cord compression. Subjects with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry. Brain metastases will not be recorded as RECIST target lesions at baseline if study allows subjects with brain metastasis (mets) * Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging (RECIST) obtained during the screening period or identified prior to signing the ICF. Subjects whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of =\< 10 mg/day of prednisone or its equivalent for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST target lesions at baseline * Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) \>= 470 ms calculated from 3 electrocardiogram (ECG)s (within 15 minutes at 5 minutes apart) * For durvalumab monotherapy and durvalumab + tremelimumab combination studies this criterion can be removed. For durvalumab +/- tremelimumab in combination with an agent with pro-arrhythmic potential or where effect of the combination on QT is not known if this criterion should be retained. Subject safety and the cardiac SKG should be consulted as needed * History of active primary immunodeficiency * Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive hepatitis B virus \[HBV\] surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA) * Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) * Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Subjects, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP * Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or180 days after the last dose of durvalumab + tremelimumab combination therapy * Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients * Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment * Determined by the investigator that the subject is unsuitable to participate in the study and the subject is unlikely to comply with study procedures, restrictions and requirements * Known allergy or hypersensitivity to IP or any excipient **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Los Angeles **Country:** United States **Facility:** UCLA / Jonsson Comprehensive Cancer Center **State:** California **Zip:** 90095 #### Overall Officials **Official 1:** **Affiliation:** UCLA / Jonsson Comprehensive Cancer Center **Name:** Albert J Chang **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - 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: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrent - ID: M8945 - Name: Genital Neoplasms, Female - Relevance: HIGH - As Found: Female Reproductive System Neoplasm - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - 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: D000009369 - Term: Neoplasms - ID: D000005833 - Term: Genital Neoplasms, Female - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000082082 - Term: Immune Checkpoint Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M4230 - Name: Antibodies, Monoclonal - Relevance: HIGH - As Found: Immunotherapy - ID: M272500 - Name: Durvalumab - Relevance: HIGH - As Found: Immunotherapy - ID: M10184 - Name: Immunoglobulins - Relevance: HIGH - As Found: Colorectal Cancer - ID: M10122 - Name: Immunoglobulin G - Relevance: HIGH - As Found: Optional - ID: M19117 - Name: Immunoglobulins, Intravenous - Relevance: LOW - As Found: Unknown - ID: M288326 - Name: Tremelimumab - Relevance: HIGH - As Found: CAM - ID: M1348 - Name: Ipilimumab - Relevance: HIGH - As Found: CAM - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000613593 - Term: Durvalumab - ID: D000074324 - Term: Ipilimumab - ID: C000520704 - Term: Tremelimumab - ID: D000007136 - Term: Immunoglobulins - ID: D000000911 - Term: Antibodies, Monoclonal - ID: D000007074 - Term: Immunoglobulin G ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05939479 **Acronym:** CePasR **Brief Title:** Antistaphylococcal Betalactam and Emergence of Resistance **Official Title:** Impact of Antistaphylococcal Penicillins and Cefazolin on the Emergence of Resistance in French Hospitals #### Organization Study ID Info **ID:** 2023PI051 #### Organization **Class:** OTHER **Full Name:** Central Hospital, Nancy, France ### Status Module #### Completion Date **Date:** 2023-06-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-11 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-05-01 **Type:** ACTUAL #### Start Date **Date:** 2018-01-01 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2023-07-11 **Type:** ACTUAL **Study First Submit Date:** 2023-06-23 **Study First Submit QC Date:** 2023-07-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Central Hospital, Nancy, France #### Responsible Party **Investigator Affiliation:** Central Hospital, Nancy, France **Investigator Full Name:** LEFEVRE Benjamin **Investigator Title:** M.D. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Antistaphylococcal penicillins are recommanded as first-line agent in methicillin-suceptible Staphylococcus aureus bacteraemia. Several studies in progress are investigating the efficacy and safety of cefazolin compared with antistaphylococcal penicillins. Cefazolin has broader spectrum than antistaphylococcal penicillins. The hypothesis of this project is that cefazoline could be responsible for a higher rate of bacterial resistance. The aim is to study the association between the emergence of bacterial resistance and the consumption of cefazolin and antistaphylococcal penicillins. ### Conditions Module **Conditions:** - Bacterial Resistance - Methicillin-Sensitive Staphylococcus Aureus Infection **Keywords:** - cefazolin - antistaphylococcal penicillins - Methicillin-Sensitive Staphylococcus Aureus Infection - Bacterial Resistance ### Design Module #### Design Info **Observational Model:** ECOLOGIC_OR_COMMUNITY **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 644 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** The total consumption of antibiotics (expressed as number of Defined Daily Doses (DDD) per 1000 inhabitants per day) will be correlate with the resistant bacteria emergence (only incidence for each bacterial strain) **Measure:** Association between the cefazolin/antistaphylococcal penicillins consumptions and the resistant bacteria emergence **Time Frame:** Between the first january 2018 and the 31st december 2022 #### Secondary Outcomes **Description:** Factors associated with the emergence of resistant bacteria will be described by a Cox model: hospital size (number of beds), location in France, activities (intensive care, surgery, etc.), type of antibiotics and intensity of consumption expressed in number of defined daily doses (DDD). **Measure:** Factors associated with the emergence of resistant bacteria **Time Frame:** Between the first january 2018 and the 31st december 2022 **Description:** Factors associated with the emergence of resistant bacteria will be described by a Cox model: hospital size (number of beds), location in France, activities (intensive care, surgery, etc.) and type of bacterial strain indentified (resistant or not). **Measure:** Factors associated with the consumption of antibiotics **Time Frame:** Between the first january 2018 and the 31st december 2022 **Description:** For each year, bacterial resistance will be described, in France and in each hospital, in the form of a quantitative variable: number of resistant bacterial strains isolated for each year (number of resistant strains / total number of strains). **Measure:** Evolution of resistance in French hospitals **Time Frame:** Between the first january 2018 and the 31st december 2022 **Description:** For each year, antibiotic consumption will be described, in France and in each hospital, in the form of a quantitative variable (expressed as number of Defined Daily Doses (DDD) per 1000 inhabitants per day) **Measure:** Evolution of antibiotics consumption in French hospitals **Time Frame:** Between the first january 2018 and the 31st december 2022 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: French hospitals which have collected their consumption and resistance data on the French national database named CONSORES (From 2019 to 2022) Exclusion Criteria: * None **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** All the patients hospitalized in included French hospitals ### Contacts Locations Module #### Locations **Location 1:** **City:** Nancy **Country:** France **Facility:** Lefevre **State:** Lorraine **Zip:** 54500 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007239 - Term: Infections - ID: D000007154 - Term: Immune System Diseases - ID: D000016908 - Term: Gram-Positive Bacterial Infections - ID: D000001424 - Term: Bacterial Infections - ID: D000001423 - Term: Bacterial Infections and Mycoses ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - 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: M10018 - Name: Hypersensitivity - Relevance: HIGH - As Found: Sensitive - ID: M15996 - Name: Staphylococcal Infections - Relevance: HIGH - As Found: Staphylococcus Aureus Infection - ID: M10200 - Name: Immune System Diseases - 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 ### Condition Browse Module - Meshes - ID: D000013203 - Term: Staphylococcal Infections - ID: D000006967 - Term: Hypersensitivity ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M5687 - Name: Cefazolin - Relevance: LOW - As Found: Unknown - ID: M13317 - Name: Penicillins - Relevance: LOW - As Found: Unknown - ID: M25772 - Name: beta-Lactams - Relevance: LOW - As Found: Unknown - ID: M11688 - Name: Methicillin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04101279 **Brief Title:** Midurethral Synthetic Tape With Tension Control Mechanism Versus Midurethral Free Tape **Official Title:** Evaluation of the Effectiveness and Safety of the Midurethral Synthetic Tape With Tension Control Mechanism and Midurethral Tension Free Tape #### Organization Study ID Info **ID:** MoscowSUMD #### Organization **Class:** OTHER **Full Name:** Moscow State University of Medicine and Dentistry ### Status Module #### Completion Date **Date:** 2019-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2019-09-24 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-23 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-10 **Type:** ESTIMATED #### Start Date **Date:** 2018-04-01 **Type:** ACTUAL **Status Verified Date:** 2019-09 #### Study First Post Date **Date:** 2019-09-24 **Type:** ACTUAL **Study First Submit Date:** 2019-06-14 **Study First Submit QC Date:** 2019-09-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Moscow State University of Medicine and Dentistry #### Responsible Party **Investigator Affiliation:** Moscow State University of Medicine and Dentistry **Investigator Full Name:** Gevorg Kasyan **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:** This is a prospective, comparative randomized controled trial. The general purposes of this study is to compare the efficacy and safety of midurethral synthetic tape with tension control mechanism and conventional midurethral tension free tape as surgical treatment for female urinary stress incontinence. ### Conditions Module **Conditions:** - Urinary Stress Incontinence **Keywords:** - stress urinary incontinence - midurethral tension free tape - patient reported outcome - bladder outlet obstruction - complications - tension control mechanism ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomized controlled comparative study ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 120 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: surgical management of stress urinary incontinence with synthetic tape with tension control mechanism. **Label:** Midurethral synthetic tape with tension control mechanism **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Procedure: surgical management of stress urinary incontinence with midurethral tension free tape. **Label:** midurethral tension free tape **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - midurethral tension free tape **Description:** Standard protocol for the surgical treatment of stress urinary incontinence using a transobturator approach. **Name:** surgical management of stress urinary incontinence with midurethral tension free tape. **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Midurethral synthetic tape with tension control mechanism **Description:** Standard protocol for the surgical treatment of stress urinary incontinence using a transobturator approach. A absorbing gasket attached to the middle of the tape provides tension control. **Name:** surgical management of stress urinary incontinence with synthetic tape with tension control mechanism. **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** The UDI measures the impact of urinary incontinence on activities, roles, and emotional states in women. This questionnaire presented six questions related to urinary disorders. The patient could answer "Not at all", "A little bit", "Moderately" or "Greatly", to each of the questions, each answer is evaluated at 0, 1, 2 or 3 points, respectively, and then summed up. The final score means that the greater the sum of the indicators, the worse the patient's condition. This score reflects the condition of the patient before and after surgery at 12 weeks and 1 year. **Measure:** Patient reported outcome measured as urogenital distress inventory (UDI-6) will be assessed before and after surgery at 12 weeks and 1 year. **Time Frame:** 1 year #### Secondary Outcomes **Description:** When the urodynamic research indicators deviate (Qmax \< 12 ml/s and Postvoid residual volume (PVR) \> 100 ml, we establish a diagnosis bladder outlet obstruction. **Measure:** Bladder outlet obstruction measured during urodynamics pressure flow study **Time Frame:** 1 year **Description:** Objective cure rate will be not the leakage at physical examination cough test with full bladder (200-400ml) **Measure:** Stress cough test measured before and after surgery. **Time Frame:** 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Women suffering from stress urinary incontinence, mixed urinary incontinence with prevalence stress urinary incontinence Exclusion Criteria: * Pregnancy * Women with neurogenic bladder dysfunction * Recurrent stress urinary incontinence * Woman with history of pelvic surgery * Mixed urinary incontinence with prevalence urgency urinary incontinence * Women who suffer from advanced POP (POP-Quantification system (POP-Q) stage more than 2) * Women with acute urinary tract infection * Women with bladder outlet obstruction * Women who are not able to give informed consent or participate with this randomized research study for any other reason **Maximum Age:** 80 Years **Minimum Age:** 21 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Lyudmila Potapova **Phone:** +7(915)248-30-20 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Sergei Sukhikh **Phone:** +7(985)307-74-50 **Role:** CONTACT #### Locations **Location 1:** **City:** Moscow **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** George Kasyan - **Phone:** +7(915)464-33-18 - **Role:** CONTACT ***Contact 2:*** - **Name:** George Kasyan - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Dmitriy Pushkar - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Sergei Sukhikh - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Lyudmila Potapova - **Role:** SUB_INVESTIGATOR **Country:** Russian Federation **Facility:** Moscow state university of medicine and dentistry named after A.I. Evdokimov **Status:** RECRUITING **Zip:** 127473 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014549 - Term: Urinary Incontinence - ID: D000014555 - Term: Urination Disorders - 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: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M5029 - Name: Urinary Bladder Neck Obstruction - Relevance: LOW - As Found: Unknown - ID: M17299 - Name: Urinary Incontinence - Relevance: LOW - As Found: Unknown - ID: M7936 - Name: Enuresis - Relevance: LOW - As Found: Unknown - ID: M17300 - Name: Urinary Incontinence, Stress - Relevance: HIGH - As Found: Urinary Stress Incontinence - ID: M17305 - Name: Urination Disorders - 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: D000014550 - Term: Urinary Incontinence, Stress ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01896479 **Acronym:** EXAMINER **Brief Title:** A Study of Two Different Doses of Cabozantinib (XL184) in Progressive, Metastatic Medullary Thyroid Cancer **Official Title:** A Randomized, Double-blind Study To Evaluate the Efficacy and Safety of Cabozantinib (XL184) at 60 mg/Day Compared to a 140 mg/Day in Progressive, Metastatic Medullary Thyroid Cancer Patients #### Organization Study ID Info **ID:** XL184-401 #### Organization **Class:** INDUSTRY **Full Name:** Exelixis ### Status Module #### Completion Date **Date:** 2023-12 **Type:** ESTIMATED #### Disp First Post Date **Date:** 2021-07-26 **Type:** ACTUAL **Disp First Submit Date:** 2021-07-13 **Disp First Submit QC Date:** 2021-07-20 #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-12 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-07 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2020-07 **Type:** ACTUAL #### Start Date **Date:** 2014-12 **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2013-07-11 **Type:** ESTIMATED **Study First Submit Date:** 2013-07-08 **Study First Submit QC Date:** 2013-07-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Exelixis #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The objective of this study is to evaluate the efficacy and safety of oral cabozantinib at a 60 mg dose compared with a 140 mg dose in subjects with progressive, metastatic MTC. It will test if the lower dose results in similar progression free survival (PFS) and overall response rate (ORR) with fewer adverse events compared to the PFS, ORR and adverse events found in previous clinical trials of 140 mg. ### Conditions Module **Conditions:** - Medullary Thyroid Cancer **Keywords:** - thyroid cancer - medullary thyroid cancer ### 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:** 247 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Cabozantinib (XL184) 140 mg as capsules and placebo tablets administered orally once a day. **Intervention Names:** - Drug: Cabozantinib (XL184) 140 mg - Drug: Placebo tablet **Label:** Cabozantinib (XL184) 140 mg **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Cabozantinib (XL184) 60 mg as tablets and placebo capsules administered orally once a day. **Intervention Names:** - Drug: Cabozantinib (XL184) 60 mg - Drug: Placebo capsule **Label:** Cabozantinib (XL184) 60 mg **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Cabozantinib (XL184) 140 mg **Name:** Cabozantinib (XL184) 140 mg **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Cabozantinib (XL184) 60 mg **Name:** Cabozantinib (XL184) 60 mg **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Cabozantinib (XL184) 140 mg **Name:** Placebo tablet **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Cabozantinib (XL184) 60 mg **Name:** Placebo capsule **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Adverse events are measured from informed consent and at least through 30 days after the date of a decision to discontinue study treatment. Assessed for up to 31 months. **Measure:** Safety and tolerability of cabozantinib as assessed by adverse events. **Time Frame:** Up to 31 months #### Primary Outcomes **Description:** PFS is measured from randomization until the date of first documented disease progression or date of death from any cause, whichever comes first. Assessed for up to 31 months. **Measure:** Progression Free Survival **Time Frame:** Up to 31 months #### Secondary Outcomes **Description:** ORR is the proportion of subjects with measurable disease at baseline and who experience a best overall response of complete response (CR) or partial response (PR) which is confirmed ≥ 28 days later. Assessed for up to 31 months. **Measure:** Objective Response Rate **Time Frame:** Up to 31 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. The subject has a histologically confirmed diagnosis of MTC. 2. All subjects will need to be tested for RET mutational status. If subjects do not have documentation confirming they have a RET mutation, a sample of their tumor (taken either during screening or from a procedure within 6 months prior to randomization) will need to be tested. 3. The subject has measurable disease per RECIST 1.1 that is metastatic as determined by the investigator based upon computerized tomography (CT), magnetic resonance imaging (MRI), PET scan, bone scan, or X-ray taken within 28 days before randomization. 4. The subject has documented worsening of disease (progressive disease) at screening as compared with a previous CT, PETor MRI scan, bone scan, or X-ray as determined by the investigator per RECIST 1.1 on qualifying screening images taken within 28 days prior to randomization as compared to previous images taken within 14 months before the qualifying screening images. 5. The subject has recovered to baseline or CTCAE v4.0 (Common Terminology Criteria for Adverse Events, version 4.0) ≤ Grade 1 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy. 6. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at screening. 7. The subject has adequate organ and marrow function 8. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document. 9. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment. Exclusion Criteria: 1. The subject has previously received cabozantinib. 2. Receipt of any type of small molecule kinase inhibitor or hormonal therapy within 28 days or 5 half-lives of the compound or active metabolites, whichever is shorter, before randomization. 3. Receipt of any systemic anti-tumor therapy within 28 days of randomization (42 days for nitrosoureas or/ mitomycin C). 4. Receipt of any other type of investigational agent within 28 days of randomization. 5. Receipt of radiation therapy within 28 days (14 days for radiation for bone metastases) of randomization or radionuclide treatment within 42 days of randomization. Subject is ineligible if there are any clinically relevant ongoing complications from prior radiation therapy. 6. The subject has untreated and/or active (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) central nervous system (CNS) metastasis. Must have completed radiation therapy ≥ 28 days prior to randomization and be stable without corticosteroids or anti-convulsant treatment for ≥ 10 days. 7. Treatment at therapeutic doses with oral anticoagulants or platelet inhibitors (examples are warfarin and clopidogrel). 8. The subject has uncontrolled, significant intercurrent illness including, but not limited to, cardiovascular disorders, gastrointestinal disorders, active infections, non-healing wounds, recent surgery. 9. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 28 days before randomization. 10. The subject is unable to swallow multiple tablets or capsules. 11. The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation. 12. The subject is pregnant or breastfeeding. 13. The subject has had a diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** St. Leonards **Country:** Australia **State:** New South Wales **Zip:** 2065 **Location 2:** **City:** Herston **Country:** Australia **State:** Queensland **Zip:** 4006 **Location 3:** **City:** Kurralta Park **Country:** Australia **State:** South Australia **Zip:** 5037 **Location 4:** **City:** Parkville **Country:** Australia **State:** Victoria **Zip:** 3050 **Location 5:** **City:** Québec **Country:** Canada **State:** Quebec **Zip:** JIH 5N4 **Location 6:** **City:** Toronto **Country:** Canada **Zip:** M5G 2M9 **Location 7:** **City:** Osijek **Country:** Croatia **Zip:** 31000 **Location 8:** **City:** Zagreb **Country:** Croatia **Zip:** 10000 **Location 9:** **City:** Zagreb **Country:** Croatia **Zip:** 1000 **Location 10:** **City:** Bordeaux **Country:** France **State:** Gironde **Zip:** 33076 **Location 11:** **City:** Angers **Country:** France **State:** Maine-et-Loire **Zip:** 49933 **Location 12:** **City:** Lyon **Country:** France **State:** Rhône **Zip:** 69373 **Location 13:** **City:** Villejuif **Country:** France **State:** Val-de-Marne **Zip:** 94805 **Location 14:** **City:** Dijon **Country:** France **Zip:** 21079 **Location 15:** **City:** Paris **Country:** France **Zip:** 75013 **Location 16:** **City:** Strasbourg Cedex **Country:** France **Zip:** 67065 **Location 17:** **City:** Budapest **Country:** Hungary **Zip:** 1088 **Location 18:** **City:** Debrecen **Country:** Hungary **Zip:** 4032 **Location 19:** **City:** Jerusalem **Country:** Israel **Zip:** 91120 **Location 20:** **City:** Petach Tikva **Country:** Israel **Zip:** 49100 **Location 21:** **City:** Safed **Country:** Israel **Zip:** 13100 **Location 22:** **City:** Catania **Country:** Italy **State:** CT **Zip:** 95124 **Location 23:** **City:** Roma **Country:** Italy **State:** RM **Zip:** 00161 **Location 24:** **City:** Sienna **Country:** Italy **State:** SI **Zip:** 53100 **Location 25:** **City:** Pisa **Country:** Italy **State:** Toscana **Zip:** 56124 **Location 26:** **City:** Milano **Country:** Italy **Zip:** 20133 **Location 27:** **City:** Padua **Country:** Italy **Zip:** 35138 **Location 28:** **City:** Torino **Country:** Italy **Zip:** 10153 **Location 29:** **City:** Goyang **Country:** Korea, Republic of **State:** Gyeonggido **Zip:** 410769 **Location 30:** **City:** Seoul **Country:** Korea, Republic of **Zip:** 110744 **Location 31:** **City:** Seoul **Country:** Korea, Republic of **Zip:** 135-710 **Location 32:** **City:** Amsterdam **Country:** Netherlands **State:** Noord Holland **Zip:** 1066 CX **Location 33:** **City:** Leiden **Country:** Netherlands **State:** Zuid-Holland **Zip:** 2333 ZA **Location 34:** **City:** Groningen **Country:** Netherlands **Zip:** 9713 GZ **Location 35:** **City:** Gliwice **Country:** Poland **State:** Slaskie **Zip:** 44-100 **Location 36:** **City:** Poznań **Country:** Poland **State:** Wielkopolskie **Zip:** 60-355 **Location 37:** **City:** Bucharest **Country:** Romania **Zip:** 10825 **Location 38:** **City:** Bucharest **Country:** Romania **Zip:** 11863 **Location 39:** **City:** Cluj-Napoca **Country:** Romania **Zip:** 400058 **Location 40:** **City:** Timisoara **Country:** Romania **Zip:** 300723 **Location 41:** **City:** Novosibirsk **Country:** Russian Federation **Zip:** 630068 **Location 42:** **City:** Obninsk **Country:** Russian Federation **Zip:** 249036 **Location 43:** **City:** St. Petersburg **Country:** Russian Federation **Zip:** 197089 **Location 44:** **City:** Yaroslavl **Country:** Russian Federation **Zip:** 150040 **Location 45:** **City:** Barcelona **Country:** Spain **Zip:** 08035 **Location 46:** **City:** Madrid **Country:** Spain **Zip:** 28034 **Location 47:** **City:** Madrid **Country:** Spain **Zip:** 28046 **Location 48:** **City:** Lund **Country:** Sweden **State:** Skane Ian **Zip:** SE-22185 **Location 49:** **City:** Uppsala **Country:** Sweden **State:** Uppsala Ian **Zip:** 75185 ### References Module #### References **Citation:** Capdevila J, Klochikhin A, Leboulleux S, Isaev P, Badiu C, Robinson B, Hughes BGM, Keam B, Parnis F, Elisei R, Gajate P, Gan HK, Kapiteijn E, Locati L, Mangeshkar M, Faoro L, Krajewska J, Jarzab B. A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg Per Day Compared with the Cabozantinib Capsule at 140 mg Per Day in Patients with Progressive, Metastatic Medullary Thyroid Cancer. Thyroid. 2022 May;32(5):515-524. doi: 10.1089/thy.2022.0027. **PMID:** 35403447 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004700 - Term: Endocrine System Diseases - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000006258 - Term: Head and Neck Neoplasms - 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: D000000230 - Term: Adenocarcinoma - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009380 - Term: Neoplasms, Nerve Tissue ### Condition Browse Module - Browse Branches - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16718 - Name: Thyroid Diseases - Relevance: HIGH - As Found: Thyroid - ID: M16723 - Name: Thyroid Neoplasms - Relevance: HIGH - As Found: Thyroid Cancer - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M20423 - Name: Carcinoma, Neuroendocrine - Relevance: HIGH - As Found: Medullary Thyroid Cancer - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: LOW - As Found: Unknown - ID: M9348 - Name: Head and Neck Neoplasms - 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: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: T5651 - Name: Thyroid Cancer, Medullary - Relevance: HIGH - As Found: Medullary Thyroid Cancer - ID: T4091 - Name: Neuroendocrine Tumor - Relevance: LOW - As Found: Unknown - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013964 - Term: Thyroid Neoplasms - ID: D000018278 - Term: Carcinoma, Neuroendocrine - ID: D000013959 - Term: Thyroid Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04105179 **Brief Title:** How TKA Implants Affect Muscle Quality and Activity During Daily Living and Immunological Response **Official Title:** Do TKA Implant Designs Affect Muscle Mass Change and Muscle Activity During Activities of Daily Living as Well as the Patient Immunological Response #### Organization Study ID Info **ID:** 20180532 #### Organization **Class:** OTHER **Full Name:** Ottawa Hospital Research Institute ### Status Module #### Completion Date **Date:** 2023-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-08-08 **Type:** ACTUAL **Last Update Submit Date:** 2022-08-05 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-12 **Type:** ESTIMATED #### Start Date **Date:** 2019-04-29 **Type:** ACTUAL **Status Verified Date:** 2022-08 #### Study First Post Date **Date:** 2019-09-26 **Type:** ACTUAL **Study First Submit Date:** 2018-09-13 **Study First Submit QC Date:** 2019-09-24 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Ottawa #### Lead Sponsor **Class:** OTHER **Name:** Ottawa Hospital Research Institute #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study compares two total knee replacement implants to asses muscle function and quality, and the immune response to the implants. 30 patients will receive the Smith and Nephew Journey II implant, while 30 patients will receive the Zimmer NexGen LPS-flex implant. 15 healthy controls will also be recruited and compared. **Detailed Description:** Patients will undergo biomechanics testing while they complete sit-to-stand, stand-to-sit, lateral step down, level walking, and single leg balance tasks up to 1 month before surgery, and 6 and 12 months after surgery. They will also undergo MRI imaging up to 1 month before surgery and 12 months after surgery to assess muscle quality. A secondary outcome will also be to analyze the immunological response in the patients who received femoral components made of oxidized zirconium versus contemporary components made of cobalt chrome. Fifteen healthy controls will also participate in the study and will undergo the biomechanical, MRI and blood draws at a single visit. ### Conditions Module **Conditions:** - Osteoarthritis, Knee - Inflammation Knees ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 75 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Group will receive the Smith \& Nephew Journey II knee implant or the Zimmer NexGen LPS-Flex knee implant **Intervention Names:** - Device: Zimmer NexGen LPS-Flex - Device: Smith & Nephew Journey II **Label:** Implant Groups **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Control group that will not be undergoing a total knee arthroplasty **Label:** Healthy Control Group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Implant Groups **Description:** Patients will be randomly assigned to 1 of 2 devices **Name:** Zimmer NexGen LPS-Flex **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Implant Groups **Description:** Patients will be randomly assigned to 1 of 2 devices **Name:** Smith & Nephew Journey II **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Peak knee extension moment will be measured by combining three-dimensional images of movement with time, the knee extension will be calculated in degrees while the participant walks at their normal walking speed. **Measure:** Change from baseline knee extension moment at 6 and 12 months during gait **Time Frame:** Baseline (within 1 month of surgery), 6 months post-surgery, and 12 months post-surgery; and versus healthy controls **Description:** Proton density fat fraction of the quadriceps and hamstrings muscles will be measured via MRI **Measure:** Change from baseline muscle quality assessed via MRI at 12 months **Time Frame:** Baseline (within 1 month of surgery), 12 months post-surgery; and versus healthy controls **Description:** Peak muscle activation of the quadriceps muscle will be measured with electromyography while the participant walks at their normal walking speed **Measure:** Change from baseline quadriceps muscle activation at 6 and 12 months during gait **Time Frame:** Baseline (within 1 month of surgery), 6 months post-surgery, and 12 months post-surgery; and versus healthy controls #### Secondary Outcomes **Description:** Peripheral blood will be collected prior to surgery and at 12 months post-surgery; for symptomatic patients, a third blood draw will occur at 24 months post-surgery. Concentrations of cobalt, chromium, and Nickle will be measured by inductively coupled plasma-mass spectrometry. **Measure:** Change in trace metal concentrations from baseline, 12 months, and 24 months **Time Frame:** Baseline (within 1 month of surgery), 12 months post-surgery, 24 months post-surgery; and versus healthy controls ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * The participants receiving a knee implant must requiring a total knee replacement Exclusion Criteria: * Any degenerative conditions (other than osteoarthritis at the affected knee) impacting joints of the lower extremities * bilateral knee replacements * previous joint replacement at the affected knee * any other past or present conditions that may impact gait * any active infection and any diagnosed conditions that may affect the local and systemic immune response (e.g., rheumatoid arthritis, HIV infection, lupus, pregnancy, and thrombocytosis) * BMI and waist circumference (WC) will be another exclusion criterion since both BMI and WC are associated with health problems and gait abnormalities. Any patient with both BMI \> 35 kg/m2 and a WC \> 102 cm in men or \> 88 cm in women will be excluded from the study. Healthy Controls Inclusion * controls must not suffer from lower extremity injuries or joint conditions that might alter gait dynamics Exclusion * BMI and waist circumference (WC) will be another exclusion criterion since both BMI and WC are associated with health problems and gait abnormalities. Any patient with both BMI \> 35 kg/m2 and a WC \> 102 cm in men or \> 88 cm in women will be excluded from the study **Healthy Volunteers:** True **Maximum Age:** 75 Years **Minimum Age:** 45 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Wade Gofton, MD FRCSC **Phone:** 6137985555 **Phone Ext:** 18779 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Meaghan Dufresne **Phone:** 613-737-8899 **Role:** CONTACT #### Locations **Location 1:** **City:** Ottawa **Country:** Canada **Facility:** The Ottawa Hospital **State:** Ontario **Status:** RECRUITING **Zip:** K1H 8L6 #### Overall Officials **Official 1:** **Affiliation:** University of Ottawa **Name:** Mario Lamontagne, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of Ottawa **Name:** Isabelle Catelas, PhD, PEng **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR **IPD Sharing:** YES ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010003 - Term: Osteoarthritis - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases - ID: D000010335 - Term: Pathologic Processes ### 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: LOW - As Found: Unknown - ID: M22168 - Name: Osteoarthritis, Knee - Relevance: HIGH - As Found: Osteoarthritis, Knee - ID: M10293 - Name: Inflammation - Relevance: HIGH - As Found: Inflammation - 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: D000020370 - Term: Osteoarthritis, Knee - ID: D000007249 - Term: Inflammation ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05024279 **Acronym:** PLANET **Brief Title:** Left Bundle Branch Area Pacing in Patients After TAVR **Official Title:** Pacing of the Left Bundle Branch Area NEcessitated After TAVR #### Organization Study ID Info **ID:** 21-0575 #### Organization **Class:** OTHER **Full Name:** Ludwig-Maximilians - University of Munich ### Status Module #### Completion Date **Date:** 2025-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-01-31 **Type:** ACTUAL **Last Update Submit Date:** 2023-01-30 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-04 **Type:** ESTIMATED #### Start Date **Date:** 2021-08-06 **Type:** ACTUAL **Status Verified Date:** 2023-01 #### Study First Post Date **Date:** 2021-08-27 **Type:** ACTUAL **Study First Submit Date:** 2021-08-09 **Study First Submit QC Date:** 2021-08-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ludwig-Maximilians - University of Munich #### Responsible Party **Investigator Affiliation:** Ludwig-Maximilians - University of Munich **Investigator Full Name:** Moritz F. Sinner **Investigator Title:** Assistant Professor **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:** Prospective, randomized, single center clinical trial to compare the outcome of left bundle branch area pacing versus right ventricular apical pacing in patients with higher degree atrio-ventricular block and a normal left ventricular function after transcatheter aortic valve replacement. **Detailed Description:** Transcatheter aortic valve replacement (TAVR) is a well-established treatment of aortic valve stenosis. Yet, requiry of permanent pacing due to new onset atrio-ventricular conduction block remains a frequent complication. Standard right ventricular pacing (RVP) at high pacing burden may lead to deterioration of left ventricular function. Left-Bundle-Area Pacing (LBBP) is a new, innovative method of physiological ventricular stimulation resulting in narrow, physiological QRS complexes. In this prospective, randomized, single center clinica trial, patients are included after TAVR and with normal left ventricular function who require pacing due to a higher degree atriao-ventricular block with an anticipated high pacing burden. Patients will be randomized to receive either left bundle branch area pacing (intervention) or right ventricular apical pacing (control). The results will confirm the feasibility of LBBP in patients following TAVR. Results will further investigate the primary outcome of a clinically relevant QRS narrowing and a combination of exploratory secondary endpoints including clinical outcomes, functional status, laboratory biomarkers, and quality of life. ### Conditions Module **Conditions:** - Aortic Valve Stenosis - AV Block - Pacing-Induced Cardiomyopathy **Keywords:** - left bundle branch area pacing - av block - right ventricular pacing - aortic valve stenosis - TAVR - ECG ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** 1:1 randomization ##### 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:** Patients are randomized to receive left bundle branch are pacing due to higher degree AV block **Intervention Names:** - Device: Left bundle branch area pacing **Label:** Intervention Arm **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients are randomized to receive standard right ventricular pacing due to higher degree AV block. **Intervention Names:** - Device: Right ventricular pacing **Label:** Control Arm **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention Arm **Description:** Left bundle branch area pacing will be applied as established in the literature using commercially available equipment. In case of unsuccessful application of left bundle branch area pacing, cross-over to right ventricular pacing is allowed. **Name:** Left bundle branch area pacing **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Control Arm **Description:** Right ventricular pacing as the standard, established form of pacing will be applied in the control group. No cross-over to the intervention arm is anticipated. **Name:** Right ventricular pacing **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Measure:** Pacemaker-associated complications **Time Frame:** 3 months **Measure:** Pacemaker-associated complications **Time Frame:** 12 months **Measure:** Pacemaker-associated complications **Time Frame:** 24 months **Description:** dichotomous yes / no **Measure:** procedural implantation success **Time Frame:** basline **Measure:** Implantation procedure duration **Time Frame:** baseline **Measure:** Fluoroscopy duration **Time Frame:** baseline **Measure:** Fluoroscopy dose **Time Frame:** baseline #### Primary Outcomes **Description:** QRS duration on 12-lead ECG, defined as earliest Q to latest S across all leads **Measure:** QRS duration **Time Frame:** 3 months #### Secondary Outcomes **Description:** QRS duration on 12-lead ECG, defined as earliest Q to latest S across all leads **Measure:** QRS duration **Time Frame:** 12 months **Description:** QRS duration on 12-lead ECG, defined as earliest Q to latest S across all leads **Measure:** QRS duration **Time Frame:** 24 months **Measure:** Death of any cause **Time Frame:** 3 months **Measure:** Death of any cause **Time Frame:** 12 months **Measure:** Death of any cause **Time Frame:** 24 months **Measure:** Death of cardio-vascular cause **Time Frame:** 3 months **Measure:** Death of cardio-vascular cause **Time Frame:** 12 months **Measure:** Death of cardio-vascular cause **Time Frame:** 24 months **Measure:** Re-hospitalization due to heart failure **Time Frame:** 3 months **Measure:** Re-hospitalization due to heart failure **Time Frame:** 12 months **Measure:** Re-hospitalization due to heart failure **Time Frame:** 24 months **Measure:** Change in left ventricular ejection fraction **Time Frame:** 3 months **Measure:** Change in left ventricular ejection fraction **Time Frame:** 12 months **Measure:** Change in left ventricular ejection fraction **Time Frame:** 24 months **Measure:** Change in echocardiographic left ventricular enddiastolic diameter **Time Frame:** 3 months **Measure:** Change in echocardiographic left ventricular enddiastolic diameter **Time Frame:** 12 months **Measure:** Change in echocardiographic left ventricular enddiastolic diameter **Time Frame:** 24 months **Measure:** Echocardiographic assessment of degreee of atrio-ventricular valve insufficiency **Time Frame:** 3 months **Measure:** Echocardiographic assessment of degreee of atrio-ventricular valve insufficiency **Time Frame:** 12 months **Measure:** Echocardiographic assessment of degreee of atrio-ventricular valve insufficiency **Time Frame:** 24 months **Measure:** Echocardiographic assessment of right ventricular ejection fraction **Time Frame:** 3 months **Measure:** Echocardiographic assessment of right ventricular ejection fraction **Time Frame:** 12 months **Measure:** Echocardiographic assessment of right ventricular ejection fraction **Time Frame:** 24 months **Measure:** Change in New York heart failure classification status **Time Frame:** 3 months **Measure:** Change in New York heart failure classification status **Time Frame:** 12 months **Measure:** Change in New York heart failure classification status **Time Frame:** 24 months **Measure:** Change in laboratory biomarkers NT-proBNP **Time Frame:** 3 months **Measure:** Change in laboratory biomarkers NT-proBNP **Time Frame:** 12 months **Measure:** Change in laboratory biomarkers NT-proBNP **Time Frame:** 24 months **Measure:** Change in functional status by 6 minute walk **Time Frame:** 3 months **Measure:** Change in functional status by 6 minute walk **Time Frame:** 12 months **Measure:** Change in functional status by 6 minute walk **Time Frame:** 24 months **Measure:** Change in EQ-5D quality of life **Time Frame:** 3 months **Measure:** Change in EQ-5D quality of life **Time Frame:** 12 months **Measure:** Change in EQ-5D quality of life **Time Frame:** 24 months **Measure:** Occurence of arrhythmias **Time Frame:** 3 months **Measure:** Occurence of arrhythmias **Time Frame:** 12 months **Measure:** Occurence of arrhythmias **Time Frame:** 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Successful TAVR implantation for classical (high flow high gradient), symptomatic aortic valve stenosis * LVEF ≥50% * Guideline-based indication for pacing due to AV block III°, AV block II°, or symptomatic bradycardic atrial fibrillation with an expecteed ventricular pacing burden \>20% * Signed informeed conseent to study participation Exclusion Criteria: * LVEF \<50% * Expected pacing burden \<20% * Pre-existing implanted cardiac device * Participation in a concurring interventional trial * age \<18 years * Current preegnancy * life expectancy \<6 months **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Munich **Country:** Germany **Facility:** LMU Klinikum **State:** BY **Zip:** 81377 #### Overall Officials **Official 1:** **Affiliation:** LMU Klinikum, Dept. of Cardiology **Name:** Moritz F Sinner, MD, MPH **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** LMU Klinikum, Dept. of Cardiology **Name:** Stephanie Fichtner, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000082862 - Term: Aortic Valve Disease - ID: D000006349 - Term: Heart Valve Diseases - ID: D000014694 - Term: Ventricular Outflow Obstruction - ID: D000006327 - Term: Heart Block - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000075224 - Term: Cardiac Conduction System Disease - ID: D000010335 - Term: Pathologic Processes ### 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: M12154 - Name: Cardiomyopathies - Relevance: HIGH - As Found: Cardiomyopathy - ID: M6475 - Name: Constriction, Pathologic - Relevance: LOW - As Found: Unknown - ID: M4340 - Name: Aortic Valve Stenosis - Relevance: HIGH - As Found: Aortic Valve Stenosis - ID: M27765 - Name: Atrioventricular Block - Relevance: HIGH - As Found: AV Block - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M2379 - Name: Aortic Valve Disease - Relevance: LOW - As Found: Unknown - ID: M9437 - Name: Heart Valve Diseases - Relevance: LOW - As Found: Unknown - ID: M17440 - Name: Ventricular Outflow Obstruction - Relevance: LOW - As Found: Unknown - ID: M9415 - Name: Heart Block - Relevance: LOW - As Found: Unknown - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M1472 - Name: Cardiac Conduction System Disease - Relevance: LOW - As Found: Unknown - ID: T449 - Name: Aortic Valve Stenosis - Relevance: HIGH - As Found: Aortic Valve Stenosis ### Condition Browse Module - Meshes - ID: D000009202 - Term: Cardiomyopathies - ID: D000001024 - Term: Aortic Valve Stenosis - ID: D000054537 - Term: Atrioventricular Block ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04623879 **Brief Title:** Real Life Evaluation of the Multi-organ Effects of Lumacaftor/Ivacaftor on F508del Homozygous Cystic Fibrosis Patients. **Official Title:** Real Life Evaluation of the Multi-organ Effects of Lumacaftor/Ivacaftor on F508del Homozygous Cystic Fibrosis Patients. #### Organization Study ID Info **ID:** CMC-16-0108-CTIL #### Organization **Class:** OTHER **Full Name:** Carmel Medical Center ### Status Module #### Completion Date **Date:** 2020-02-26 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-02-03 **Type:** ACTUAL **Last Update Submit Date:** 2021-02-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-07-30 **Type:** ACTUAL #### Start Date **Date:** 2016-12-29 **Type:** ACTUAL **Status Verified Date:** 2021-02 #### Study First Post Date **Date:** 2020-11-10 **Type:** ACTUAL **Study First Submit Date:** 2020-10-12 **Study First Submit QC Date:** 2020-11-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Carmel Medical Center #### Responsible Party **Investigator Affiliation:** Carmel Medical Center **Investigator Full Name:** Karin Yaakobi Bianu **Investigator Title:** Senior physician, Pediatric Pulmonology Unit and CF Center **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Background: Lumacaftor/Ivacaftor (LUM-IVA), a CFTR corrector-potentiator combination, was found to improve lung function and reduce pulmonary exacerbations (PEx). However, cystic fibrosis (CF) is a multi-organ disease and therefore there is a need for more information on the systemic effects of CFTR modulators. Aim: To evaluate pancreatic function, bone metabolism and respiratory changes through a year of LUM-IVA treatment. Methods: A prospective real world, one-year study on F508del homozygous adult CF patients who commenced treatment with LUM-IVA. Visits were scheduled on the first day of treatment and every 3 months evaluating: symptoms, Body Mass Index (BMI), spirometry, laboratory tests and Quality of life. At baseline and at 12 months, the patients underwent sweat test, oral glucose tolerance test (OGTT), chest CT and dual-energy X-ray absorptiometry (DEXA). **Detailed Description:** Introduction Cystic fibrosis (CF) is a genetic multisystem disease that is characterized by pancreatic insufficiency (PI) and chronic airway infections associated with loss of lung function, repeated pulmonary exacerbations (PEx), and ultimately, respiratory failure. F508del, the deletion of a single amino acid, is the most common mutation that causes CF. In July 2015, the U.S. Food and Drug Administration approved the combination Lumacaftor/Ivacaftor (Orkambi®, Vertex pharmaceuticals) for use in patients with CF homozygous for the F508del mutation. Briefly, this combination of a corrector (Lumacaftor) and potentiator (Ivacaftor) partially restores the activity of the membranous CF transmembrane regulator (CFTR) protein. Lumacaftor improves the processing of F508del CFTR and its transport to the cell surface, while Ivacaftor increases the probability for the channel to be open and its transport of chloride. In clinical trials, treatment with Lumacaftor-Ivacaftor (LUM-IVA) in individuals homozygous for F508del led to an increase in lung function, weight, and a significant reduction in the frequency of PEx and CF-related hospitalizations. Extra-pulmonary complications are common in CF. Of these, CF-related diabetes (CFRD) is one of the worst prognostic factors. In people with gating mutations responsive to Ivacaftor, treatment was associated with an improvement in insulin secretion after glucose challenge. Another important extra-pulmonary complication is CF bone disease (CFBD), characterized by low bone mineral density. Osteopenia and fractures are noted among 50-75% of patients diagnosed with CF. The reasons for those pathologies are malabsorption of fat soluble vitamins, a complex abnormality of sex hormone composition, primary CFTR dysfunction, chronic infection and inflammation, and low levels of bone-building exercise resulting from advanced respiratory compromise. It is well known that growth and sexual development is delayed in CF patients, due in part to nutritional deficiencies and the severity of their chronic lung disease. These delays are accompanied by low levels of sex hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The aim of the current study was to evaluate endocrine pancreatic function, bone metabolism and respiratory changes through the first year of LUM-IVA treatment in adult patients. Materials and methods Study design and participants The study was a prospective, single center, observational real-world study on F508del homozygous adult CF patients, who commenced treatment with LUM-IVA and were followed for a year. Pregnant and nursing females; solid organ or hematological transplant recipients; alcohol or drug abusers; patients with an acute upper or lower respiratory infection, and those with PEx or changes in therapy for pulmonary disease within 28 days before Day 1 (first dose of study drug) were excluded. All subjects received 400 mg Lumacaftor /250 mg Ivacaftor (LUM-IVA) fixed-dose combination film coated tablets for oral administration every12 hours. All participants remained on their pre-study stable CF medication regimen through the year. They were followed in the CF Center at Carmel Medical Center, Haifa, Israel between 2016 and 2019. The institutional board reviewed and approved the study protocol. All patients provided written informed consent. Study period Screening period was from day -28 through day -1. Treatment period was from day 1 (first dose of study drug) through 12 months ± 7 days. Five clinic visits were carried out on day 1 and at weeks 12, 24, 36 and 48 (± 7 days). At screening (V0) and at 12 months (V5) the patients underwent a sweat test, Oral glucose tolerance test (OGTT) in patients without CF related diabetes (CFRD), chest computed tomography (CT) and a bone density evaluation using Dual-energy x-ray absorptiometry (DEXA). Evaluations performed during each visit included: recording of CF-related symptoms, treatments, physical examination, vital signs, body mass index (BMI) measurements, pulmonary function tests (PFT), laboratory tests, sputum culture and disease-specific quality of life evaluation using the Cystic Fibrosis Questionnaire-Revised (CFQR). Study assessments The primary endpoint was the absolute change from baseline through 12 months in the percentage of predicted Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and forced expiratory flow between 25-75 (FEF25-75). Spirometry was performed in accordance with the American Thoracic Society/ European Respiratory Society (ATS/ERS ) Task Force, using a KoKo® spirometer (n-Spire Healthcare, Inc., Longmont CO, USA). Key secondary endpoints included the absolute and relative change from baseline through 12 months in (1) metabolic factors, including BMI, OGTT (75g of glucose were ingested orally, and glucose, insulin \& c-peptide were examined at the time of ingestion, 1 hour and 2 hours later), Albumin and HbA1C; (2) bone health factors including parathyroid hormone (PTH), Alkaline phosphatase, , Phosphor, and Calcium levels; A, D, E vitamin levels, Urine Ca/Cr ratio; and DEXA scans (3) Hormonal factors including; luteinizing hormone (LH), follicle stimulating hormone (FSH), Testosterone and Estradiol levels; and (4) evaluation of CFTR function through concentration of sweat chloride Additional evaluations included (1) chest CT scans that were performed and scored using the Bhalla scoring method by a radiologist-investigator (the total score ranges from 9 to 25, with a higher score indicating more severe structural lung changes); (2) The patient-reported CFQ-R respiratory domain score (scores range from 0 to 100, with higher scores indicating a better quality of life and 4 points considered to be a minimal clinically important difference) (3) safety parameters (electrolytes, liver and kidney function test, coagulation function) and (3) pulmonary exacerbations (PEx). A PEx was defined as a deterioration in respiratory symptoms that led to a change in treatment. Each PEx was counted as a separate event, and the number of PEx in the year prior to commencing treatment with LUM-IVA was compared to PEx in the year on the treatment. We documented: number of exacerbations, oral vs. intravenous antibiotic treatment, hospitalizations, presence of fever \>38°C, laboratory parameters (white blood cells count \[WBC\], absolute neutrophil count \[ANC\], C-reactive protein \[CRP\] at PEx start in hospitalized patients), sputum culture results and time to next PEx. ### Conditions Module **Conditions:** - Cystic Fibrosis **Keywords:** - CFTR modulators - Lumacaftor/ Ivacaftor - Bone metabolism - Pancreatic function ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 13 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** F508del homozygous adult CF patients who commenced treatment with LUM-IVA **Intervention Names:** - Drug: Lumacaftor, Ivacaftor Drug Combination **Label:** F508del homozygous adult CF patients ### Interventions #### Intervention 1 **Arm Group Labels:** - F508del homozygous adult CF patients **Name:** Lumacaftor, Ivacaftor Drug Combination **Other Names:** - Orkambi **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** the absolute change from baseline through 12 months in the percentage of predicted Forced expiratory volume in 1 second (FEV1). **Measure:** Pulmonary function tests **Time Frame:** 1 year #### Secondary Outcomes **Description:** weight and height will be combined to report BMI in kg/m\^2 **Measure:** BMI **Time Frame:** 1 year **Description:** Alkaline phosphatase - absolute and relative change from baseline ( every 3 months under treatment) **Measure:** bone parameters **Time Frame:** 1 year **Description:** DEXA scans **Measure:** bone health factors **Time Frame:** 1 year **Description:** the absolute change from baseline through 12 months in the percentage of predicted forced expiratory flow between 25-75 (FEF25-75). **Measure:** Additional Pulmonary function tests **Time Frame:** 1 year **Description:** OGTT (75g of glucose were ingested orally, and glucose was examined at the time of ingestion, 1 hour and 2 hours later)- we will report the glucose parameter of OGTT test. **Measure:** Glucose metabolism **Time Frame:** The change between 12 months (under treatment) to screening ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects who meet all of the following inclusion criteria will be eligible for this study: 1. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, and other study procedures. 2. Subjects (males and females), will be aged 18 years or older 3. Confirmed diagnosis of CF 4. Homozygous for the F508del-CFTR mutation. 5. Willing to remain on a stable CF medication regimen through 12 months. Exclusion Criteria: * Subjects who meet any of the following exclusion criteria will not be eligible for this study: 1. History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. For example: • History of cirrhosis with portal hypertension, and/or history of risk factors for Torsade de Pointes (e.g., familial long QT syndrome, hypokalemia, heart failure, left ventricular hypertrophy, bradycardia, myocardial infarction, cardiomyopathy, history of arrhythmia \[ventricular and atrial fibrillation\]), obesity, acute neurologic events. 2. Any of the following abnormal laboratory values at Screening: * Abnormal liver function defined as any 2 or more of the following: ≥3 × upper limit of normal (ULN) aspartate aminotransferase (AST), ≥3 × ULN alanine aminotransferase (ALT), ≥3 × ULN gamma-glutamyl transpeptidase (GGT), ≥3 × ULN alkaline phosphatase (ALP), or ≥2 × ULN total bilirubin * Abnormal liver function defined as any increase of ≥5 × ULN AST or ALT * Abnormal renal function defined as glomerular filtration rate ≤50 mL/min/1.73 m2 3. An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug). 4. History of solid organ or hematological transplantation. 5. History or evidence of cataract, lens opacity, Y-suture, or lamellar rings determined to be clinically significant by the ophthalmologist during the ophthalmologic examination during the Screening Period. 6. History of alcohol or drug abuse in the past year, including but not limited to cannabis, cocaine, and opiates, as deemed by the investigator. 7. Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at Screening and Day 1. **Maximum Age:** 99 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** F508del homozygous adult CF patients, who commenced treatment with LUM-IVA in a single center ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Carmel Medical Center **Name:** Karin Yaacoby-Bianu, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi: 10.1056/NEJMoa1409547. Epub 2015 May 17. **PMID:** 25981758 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000010182 - Term: Pancreatic Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000007232 - Term: Infant, Newborn, Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M6755 - Name: Cystic Fibrosis - Relevance: HIGH - As Found: Cystic Fibrosis - ID: M8485 - Name: Fibrosis - Relevance: HIGH - As Found: Fibrosis - ID: M13102 - Name: Pancreatic 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: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M10276 - Name: Infant, Newborn, Diseases - Relevance: LOW - As Found: Unknown - ID: T1710 - Name: Cystic Fibrosis - Relevance: HIGH - As Found: Cystic Fibrosis ### Condition Browse Module - Meshes - ID: D000003550 - Term: Cystic Fibrosis - ID: D000005355 - Term: Fibrosis ### Intervention Browse Module - Ancestors - ID: D000065101 - Term: Chloride Channel Agonists - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M250281 - Name: Ivacaftor - Relevance: HIGH - As Found: Laryngeal ### Intervention Browse Module - Meshes - ID: C000545203 - Term: Ivacaftor ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00872079 **Brief Title:** Personalized Warfarin Dosing by Genomics and Computational Intelligence **Official Title:** Personalized Warfarin Dosing Using Genomics and Computational Intelligence #### Organization Study ID Info **ID:** CAMM-04-07S #### Organization **Class:** FED **Full Name:** VA Office of Research and Development ### Status Module #### Completion Date **Date:** 2011-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-02-24 **Type:** ESTIMATED **Last Update Submit Date:** 2014-02-21 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2011-09 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-02-24 **Type:** ESTIMATED **Results First Submit Date:** 2014-02-21 **Results First Submit QC Date:** 2014-02-21 #### Start Date **Date:** 2008-09 **Status Verified Date:** 2014-02 #### Study First Post Date **Date:** 2009-03-31 **Type:** ESTIMATED **Study First Submit Date:** 2009-03-27 **Study First Submit QC Date:** 2009-03-27 **Why Stopped:** Lack of Funding ### Sponsor Collaborators Module #### Lead Sponsor **Class:** FED **Name:** US Department of Veterans Affairs #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will create a computer program that can be used to help dose a drug called warfarin for the prevention of blood clotting. The study will collected specific information about those patients receiving this drug and use that information to create a computer program that will predict the effects of the drug. With this prediction program in place, the investigators can perform a series of "what if I gave this amount of drug" simulations to determine the best dose of drug for that patient. Once the computer programs are developed, the investigators will test the program in patients that actually need this drug. They will also include genetic information into the prediction since it has been shown that this information can affect how well the drug works. Patients will have this genetic information determined during this study. **Detailed Description:** The objective of this project is to develop new techniques to incorporate genomic data into pharmacodynamic models to improve the dosing of chronically administered drugs. Specifically, the investigators look to improve warfarin therapy by decreasing the variability in the effect of this drug using information about the subjects genotype and computational intelligence. The investigators propose to achieve our objectives using a prospective, randomized, controlled clinical trial of a computer program that they will develop from both historical and prospective data. This computer program will be tested against a control group using standard warfarin dosing, and a group using standard dosing plus subject genotype. Warfarin dose and response data will be obtained from patients seen in the Louisville VA anticoagulation clinic. Following informed consent, subject genotype for cytochrome P450 allele 2C9 (2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) will be determined. Other data routinely obtained to aid in warfarin dosing will also be recorded. Using this information, the investigators will develop many different models for warfarin dosing using incrementally more information. Each of these models will be tested using computer simulation until they have obtained the best model. This model will be used in a pilot study to test performance in real time. The results of the pilot study will then be used to power a final clinical trial of standard dosing, standard dosing and genetic information, computer dosing, and computer dosing plus genetic information. The specific aims of this research are: 1. Determine the structure and the type of neural network model for predictions from historically obtained data. (Computer Model) 2. Prospectively develop an individualized neural network and nonlinear mixed effect modelling (NONMEM) model capable of predicting erythropoietin dosing for chronic in-center hemodialysis patients using adaptive techniques. 3. Develop computer programs based on neural computing that can be used in a clinical setting. (Computer Model) 4. Determine the utility of the computer programs prospectively in the clinical setting. ### Conditions Module **Conditions:** - Venous Thrombosis - Atrial Fibrillation - Myocardial Infarction **Keywords:** - warfarin - pharmacokinetics - pharmacodynamics ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 175 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Aim 1: Collect historical data on warfarin dosing in subjects at the VA. Aim 2: Collect genotype information on up to 300 subjects receiving warfarin anticoagulation. Aim 3: Develop a computer model incorporating the information from Aim 1 and 2. Aim 4: Conduct randomized clinical trial. **Intervention Names:** - Device: Genomics **Label:** Genomics **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Genomics **Description:** Model predictive control is a computer based algorithm that can be applied to drug dosing. This computer tool uses a model of how a patient will respond to a drug dose based on demographic and historical dosing information to predict a new drug response. A drug dose controller applies all possible doses to the response model and selects the one dose that best meets the stated goals of the drug therapy. In the case of warfarin, we will calculate an international normalized ratio (INR) value within a specific target range. **Name:** Genomics **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** During Aim 2, Determined Patient Genotypes: CYP2C9 and VKORC1. **Measure:** Patient Genomics **Time Frame:** Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Warfarin therapy * Attend anticoagulation clinic * Warfarin therapy for 6 months Exclusion Criteria: * History of non-compliance **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Louisville **Country:** United States **Facility:** VA Medical Center, Louisville **State:** Kentucky **Zip:** 40206 #### Overall Officials **Official 1:** **Affiliation:** VA Medical Center, Louisville **Name:** Michael E. Brier, PhD **Role:** PRINCIPAL_INVESTIGATOR ## 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 - ID: D000007511 - Term: Ischemia - ID: D000009336 - Term: Necrosis - ID: D000017202 - Term: Myocardial Ischemia - ID: D000014652 - Term: Vascular Diseases - ID: D000016769 - Term: Embolism and Thrombosis ### 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: M12155 - Name: Myocardial Infarction - Relevance: HIGH - As Found: Myocardial Infarction - ID: M10282 - Name: Infarction - Relevance: HIGH - As Found: Infarction - ID: M4586 - Name: Atrial Fibrillation - Relevance: HIGH - As Found: Atrial Fibrillation - ID: M16686 - Name: Thrombosis - Relevance: HIGH - As Found: Thrombosis - ID: M22071 - Name: Venous Thrombosis - Relevance: HIGH - As Found: Venous Thrombosis - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M12284 - Name: Necrosis - 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: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M7784 - Name: Embolism - Relevance: LOW - As Found: Unknown - ID: M19128 - Name: Embolism and Thrombosis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001281 - Term: Atrial Fibrillation - ID: D000009203 - Term: Myocardial Infarction - ID: D000013927 - Term: Thrombosis - ID: D000020246 - Term: Venous Thrombosis - ID: D000007238 - Term: Infarction ### Intervention Browse Module - Browse Branches - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17602 - Name: Warfarin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Genomics **Description:** Model Predictive Control: Model predictive control is a computer based algorithm that can be applied to drug dosing. This computer tool uses a model of how a patient will respond to a drug dose based on demographic and historical dosing information to predict a new drug response. A drug dose controller applies all possible doses to the response model and selects the one dose that best meets the stated goals of the drug therapy. In the case of warfarin, we will calculate an INR value within a specific target range. **ID:** EG000 **Title:** Genomics **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 175 **Units:** Participants ### Group **ID:** BG000 **Title:** Genomics **Description:** The specific aims of this research are: 1. Determine the structure and the type of neural network model for predictions from historically obtained data. (Computer Model) 2. Prospectively develop an individualized neural network and NONMEM model capable of predicting erythropoietin dosing for chronic in-center hemodialysis patients using adaptive techniques. 3. Develop computer programs based on neural computing that can be used in a clinical setting. (Computer Model) 4. Determine the utility of the computer programs prospectively in the clinical setting. ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 50 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 125 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 10 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 165 **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:** 1 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 17 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 157 **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:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** University of Louisville **Phone:** 502-852-0246 **Title:** Michael Brier ## Results Section - Outcome Measures Module ### Outcome Measure 1 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 112 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** During Aim 2, Determined Patient Genotypes: CYP2C9 and VKORC1. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** Baseline **Title:** Patient Genomics **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** Model Predictive Control: Model predictive control is a computer based algorithm that can be applied to drug dosing. This computer tool uses a model of how a patient will respond to a drug dose based on demographic and historical dosing information to predict a new drug response. A drug dose controller applies all possible doses to the response model and selects the one dose that best meets the stated goals of the drug therapy. In the case of warfarin, we will calculate an INR value within a specific target range. There are 4 Aims in this study. 1. To collect historical data on warfarin dosing in subjects. 2. To collect genotype information on up to 300 subjects receiving warfarin anticoagulation. 3. to develop a computer model incorporating the information from aim 1 and aim 2. 4. To conduct a randomized clinical trial. **ID:** OG000 **Title:** Genomics ### Participant Flow Module #### Group **Description:** Model Predictive Control: Model predictive control is a computer based algorithm that can be applied to drug dosing. This computer tool uses a model of how a patient will respond to a drug dose based on demographic and historical dosing information to predict a new drug response. A drug dose controller applies all possible doses to the response model and selects the one dose that best meets the stated goals of the drug therapy. In the case of warfarin, we will calculate an INR value within a specific target range. **ID:** FG000 **Title:** Genomics #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 175 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 175 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Pre-Assignment Details:** Participants were not enrolled into the randomized clinical trial for Aim 4 due to lack of funding. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00886379 **Acronym:** BSS **Brief Title:** Blue Sky Study: Impact of Milk and Vitamin D for Child Growth and Health **Official Title:** Blue Sky Study: Impact of Milk and Vitamin D for Child Growth and Health #### Organization Study ID Info **ID:** BSS-103306 #### Organization **Class:** OTHER **Full Name:** Brigham and Women's Hospital ### Status Module #### Completion Date **Date:** 2009-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-03-23 **Type:** ACTUAL **Last Update Submit Date:** 2021-02-26 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2021-03-23 **Type:** ACTUAL **Results First Submit Date:** 2019-05-28 **Results First Submit QC Date:** 2021-02-26 #### Start Date **Date:** 2009-01 **Status Verified Date:** 2021-02 #### Study First Post Date **Date:** 2009-04-22 **Type:** ESTIMATED **Study First Submit Date:** 2009-04-20 **Study First Submit QC Date:** 2009-04-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Brigham and Women's Hospital #### Responsible Party **Investigator Affiliation:** Brigham and Women's Hospital **Investigator Full Name:** Janet Rich-Edwards **Investigator Title:** Direct of Developmental Epidemiology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This intervention study will address the impact of vitamin D fortified milk and vitamin D supplements on the growth, levels of vitamin D, insulin-like growth factor 1, growth hormone, academic attention, respiratory infections, asthma, and flexural dermatitis (a proxy for eczema) of Mongolian children. ### Conditions Module **Conditions:** - Vitamin d Deficiency **Keywords:** - vitamin d - children - Mongolia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 597 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Mongolian milk without D **Intervention Names:** - Dietary Supplement: Mongolian milk without vitamin D **Label:** 1 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Mongolian milk with vitamin D **Intervention Names:** - Dietary Supplement: Mongolian milk with vitamin D **Label:** 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Ultra High Temperature (UHT) milk **Intervention Names:** - Dietary Supplement: UHT milk **Label:** 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Milk Substitute **Intervention Names:** - Dietary Supplement: Milk Substitute **Label:** 4 **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Seasonal D **Intervention Names:** - Dietary Supplement: Seasonal D supplement **Label:** 5 **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** Daily D **Intervention Names:** - Dietary Supplement: Daily D supplement **Label:** 6 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** 710ml per day for 49 days **Name:** Mongolian milk without vitamin D **Other Names:** - Guum milk **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - 2 **Description:** 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **Name:** Mongolian milk with vitamin D **Other Names:** - Guum milk **Type:** DIETARY_SUPPLEMENT #### Intervention 3 **Arm Group Labels:** - 3 **Description:** 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **Name:** UHT milk **Other Names:** - Gossner milk **Type:** DIETARY_SUPPLEMENT #### Intervention 4 **Arm Group Labels:** - 4 **Description:** 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **Name:** Milk Substitute **Other Names:** - Mead Johnson **Type:** DIETARY_SUPPLEMENT #### Intervention 5 **Arm Group Labels:** - 5 **Description:** Deliver dosage of 13,700 IU vitamin D over 7 days **Name:** Seasonal D supplement **Other Names:** - Tish Con **Type:** DIETARY_SUPPLEMENT #### Intervention 6 **Arm Group Labels:** - 6 **Description:** Deliver dosage of 13,700 IU vitamin D in vitamin capsules over 49 days. **Name:** Daily D supplement **Other Names:** - Tish Con **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Baseline and Follow-up 25(OH)D3 by liquid chromatography-tandem mass spectrometry **Measure:** Serum 25-hydroxyvitamin D Concentrations in Schoolchildren **Time Frame:** Blood was analyzed at day 0 and day 49 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Children in 3rd and 4th grade from selected Mongolian schools. * School selection will consider: * socioeconomic position; * geographic location; * school size; * current lunch or supplementation program; and * the interest and willingness to participate of the school's administration and faculty. Exclusion Criteria: * Allergy to milk or wheat products. **Healthy Volunteers:** True **Maximum Age:** 11 Years **Minimum Age:** 9 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Brigham and Women's Hospital **Name:** Janet Rich-Edwards, Sc.D. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Rich-Edwards JW, Ganmaa D, Pollak MN, Nakamoto EK, Kleinman K, Tserendolgor U, Willett WC, Frazier AL. Milk consumption and the prepubertal somatotropic axis. Nutr J. 2007 Sep 27;6:28. doi: 10.1186/1475-2891-6-28. **PMID:** 17900364 **Citation:** Rich-Edwards JW, Ganmaa D, Kleinman K, Sumberzul N, Holick MF, Lkhagvasuren T, Dulguun B, Burke A, Frazier AL. Randomized trial of fortified milk and supplements to raise 25-hydroxyvitamin D concentrations in schoolchildren in Mongolia. Am J Clin Nutr. 2011 Aug;94(2):578-84. doi: 10.3945/ajcn.110.008771. Epub 2011 Jun 22. **PMID:** 21697075 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001361 - Term: Avitaminosis - ID: D000003677 - Term: Deficiency Diseases - ID: D000044342 - Term: Malnutrition - 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: M17551 - Name: Vitamin D Deficiency - Relevance: HIGH - As Found: Vitamin D Deficiency - ID: M4660 - Name: Avitaminosis - Relevance: LOW - As Found: Unknown - ID: M6879 - Name: Deficiency Diseases - Relevance: LOW - As Found: Unknown - ID: M25306 - Name: Malnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014808 - Term: Vitamin D Deficiency ### Intervention Browse Module - Ancestors - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000050071 - Term: Bone Density Conservation Agents - ID: D000077264 - Term: Calcium-Regulating Hormones and Agents ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: HIGH - As Found: Ultrasound - ID: M6003 - Name: Cholecalciferol - Relevance: HIGH - As Found: Ultrasound - ID: M17558 - Name: Vitamins - Relevance: HIGH - As Found: Every - ID: M8026 - Name: Ergocalciferols - Relevance: HIGH - As Found: Ultrasound - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M5381 - Name: Calcium - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: T442 - Name: Cholecalciferol - Relevance: HIGH - As Found: Ultrasound - ID: T479 - Name: Vitamin D3 - Relevance: HIGH - As Found: Ultrasound - ID: T440 - Name: Calciferol - Relevance: HIGH - As Found: Ultrasound - ID: T445 - Name: Ergocalciferol - Relevance: HIGH - As Found: Ultrasound - ID: T478 - Name: Vitamin D2 - Relevance: HIGH - As Found: Ultrasound ### Intervention Browse Module - Meshes - ID: D000014807 - Term: Vitamin D - ID: D000004872 - Term: Ergocalciferols - ID: D000002762 - Term: Cholecalciferol - ID: D000014815 - Term: Vitamins ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Unfortified Mongolain Milk **Deaths Num At Risk:** 101 **Description:** Mongolian milk without vitamin D: 710ml per day for 49 days **ID:** EG000 **Other Num at Risk:** 101 **Serious Number At Risk:** 101 **Title:** Unfortified Mongolain Milk **Group ID:** EG001 **Title:** Fortified Mongolian Milk **Deaths Num At Risk:** 140 **Description:** Mongolian milk with vitamin D: 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **ID:** EG001 **Other Num at Risk:** 140 **Serious Number At Risk:** 140 **Title:** Fortified Mongolian Milk **Group ID:** EG002 **Title:** Fortified UHT Milk **Deaths Num At Risk:** 137 **Description:** UHT milk: 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **ID:** EG002 **Other Num at Risk:** 137 **Serious Number At Risk:** 137 **Title:** Fortified UHT Milk **Group ID:** EG003 **Title:** Daily Vitamin D Supplements **Deaths Num At Risk:** 109 **Description:** Daily D supplement: Deliver dosage of 13,700 IU vitamin D in vitamin capsules over 49 days. **ID:** EG003 **Other Num at Risk:** 109 **Serious Number At Risk:** 109 **Title:** Daily Vitamin D Supplements **Group ID:** EG004 **Title:** Seasonal Vitamin D Supplements **Deaths Num At Risk:** 92 **Description:** Seasonal D supplement: Deliver dosage of 13,700 IU vitamin D over 7 days **ID:** EG004 **Other Num at Risk:** 92 **Serious Number At Risk:** 92 **Title:** Seasonal Vitamin D Supplements **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 101 **Group ID:** BG001 **Value:** 140 **Group ID:** BG002 **Value:** 137 **Group ID:** BG003 **Value:** 109 **Group ID:** BG004 **Value:** 92 **Group ID:** BG005 **Value:** 579 **Units:** Participants ### Group **ID:** BG000 **Title:** Unfortified Mongolain Milk **Description:** Mongolian milk without vitamin D: 710ml per day for 49 days ### Group **ID:** BG001 **Title:** Fortified Mongolian Milk **Description:** Mongolian milk with vitamin D: 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. ### Group **ID:** BG002 **Title:** Fortified UHT Milk **Description:** UHT milk: 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. ### Group **ID:** BG003 **Title:** Daily Vitamin D Supplements **Description:** Daily D supplement: Deliver dosage of 13,700 IU vitamin D in vitamin capsules over 49 days. ### Group **ID:** BG004 **Title:** Seasonal Vitamin D Supplements **Description:** Seasonal D supplement: Deliver dosage of 13,700 IU vitamin D over 7 days ### Group **ID:** BG005 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 101 #### Measurement **Group ID:** BG001 **Value:** 140 #### Measurement **Group ID:** BG002 **Value:** 137 #### Measurement **Group ID:** BG003 **Value:** 109 #### Measurement **Group ID:** BG004 **Value:** 92 #### Measurement **Group ID:** BG005 **Value:** 579 **Category Title:** <=18 years #### 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 #### Measurement **Group ID:** BG005 **Value:** 0 **Category Title:** Between 18 and 65 years #### 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 #### Measurement **Group ID:** BG005 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 51 #### Measurement **Group ID:** BG001 **Value:** 65 #### Measurement **Group ID:** BG002 **Value:** 69 #### Measurement **Group ID:** BG003 **Value:** 45 #### Measurement **Group ID:** BG004 **Value:** 41 #### Measurement **Group ID:** BG005 **Value:** 271 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 50 #### Measurement **Group ID:** BG001 **Value:** 75 #### Measurement **Group ID:** BG002 **Value:** 68 #### Measurement **Group ID:** BG003 **Value:** 64 #### Measurement **Group ID:** BG004 **Value:** 51 #### Measurement **Group ID:** BG005 **Value:** 308 **Category Title:** Male **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 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Brigham and Women's Hospital **Phone:** 617-525-7929 **Title:** Dr. Janet Rich-Edwards ## Results Section - Outcome Measures Module ### Outcome Measure 1 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4 - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4 - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 5 - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 3 - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 4 - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4 - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6 - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 10 - **Upper Limit:** - **Value:** 29 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 6 - **Upper Limit:** - **Value:** 21 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 4 - **Upper Limit:** - **Value:** 12 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Baseline and Follow-up 25(OH)D3 by liquid chromatography-tandem mass spectrometry **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Blood was analyzed at day 0 and day 49 **Title:** Serum 25-hydroxyvitamin D Concentrations in Schoolchildren **Type:** PRIMARY **Unit of Measure:** ng/ml ##### Group **Description:** Mongolian milk without vitamin D: 710ml per day for 49 days **ID:** OG000 **Title:** Unfortified Mongolain Milk ##### Group **Description:** Mongolian milk with vitamin D: 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **ID:** OG001 **Title:** Fortified Mongolian Milk ##### Group **Description:** UHT milk: 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **ID:** OG002 **Title:** Fortified UHT Milk ##### Group **Description:** Daily D supplement: Deliver dosage of 13,700 IU vitamin D in vitamin capsules over 49 days. **ID:** OG003 **Title:** Daily Vitamin D Supplements ##### Group **Description:** Seasonal D supplement: Deliver dosage of 13,700 IU vitamin D over 7 days **ID:** OG004 **Title:** Seasonal Vitamin D Supplements ### Participant Flow Module #### Group **Description:** Mongolian milk without vitamin D: 710ml per day for 49 days **ID:** FG000 **Title:** Unfortified Mongolian Milk #### Group **Description:** Mongolian milk with vitamin D: 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **ID:** FG001 **Title:** Fortified Mongolian Milk #### Group **Description:** UHT milk: 710ml per day for 49 days. A total of 13,700 IU of vitamin D over the intervention period. **ID:** FG002 **Title:** Fortified UHT Milk #### Group **Description:** Daily D supplement: Deliver dosage of 13,700 IU vitamin D in vitamin capsules over 49 days. **ID:** FG003 **Title:** Daily Vitamin D Supplements #### Group **Description:** Seasonal D supplement: Deliver dosage of 13,700 IU vitamin D over 7 days **ID:** FG004 **Title:** Seasonal Vitamin D Supplements #### Period **Title:** Overall Study ##### Withdraw **Type:** Transferred Schools ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 1 ##### Withdraw **Type:** Final blood draw not obtained ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ###### Reason **Group ID:** FG002 **Number of Subjects:** 4 ###### Reason **Group ID:** FG003 **Number of Subjects:** 2 ###### Reason **Group ID:** FG004 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 104 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 143 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 143 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 112 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 95 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 101 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 140 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 137 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 109 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 92 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 3 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02354079 **Acronym:** HYPOCHOL **Brief Title:** HYPOCHOL : A Genetically-based Strategy to Identify New Targets in Cholesterol Metabolism **Official Title:** HYPOCHOL : A Genetically-based Strategy to Identify New Targets in Cholesterol Metabolism #### Organization Study ID Info **ID:** RC14_0400 #### Organization **Class:** OTHER **Full Name:** Nantes University Hospital ### Status Module #### Completion Date **Date:** 2032-01-07 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-04 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-03 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2022-01-07 **Type:** ACTUAL #### Start Date **Date:** 2016-01-07 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2015-02-03 **Type:** ESTIMATED **Study First Submit Date:** 2015-01-14 **Study First Submit QC Date:** 2015-01-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nantes University Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this study is to identify new targets in cholesterol metabolism thanks to a genetically-based strategy. **Detailed Description:** The goal is to recruit 400 subjects: 200 adult subjects with familial hypobetalipoproteinemia (FHBL) (index cases) plus 200 additional related subjects in at least 10 large informative FHBL families, in which there is no known mutation in FHBL genes. The patient care is modified: patient will have an Hospital Anxiety and Depression (HAD) questionnaire (focus on depressive syndrome), a food diary, and some additional blood analysis (including genetic analysis). One of the main issue to recruit FHBL patients is the fact that they are asymptomatic and that FHBL is not identified as a serious illness by their general physicians. Step-1. Excluding mutations in selected candidate genes As a first approach to screen candidate genes and exclude patients with known mutations, the investigators developed a custom design based on the Haloplex™ technology (Agilent® Technologies) to perform high-throughput sequencing of the coding regions of 10 genes, including those previously described in FHBL (apolipoprotein B (APOB), Proprotein convertase subtilisin/kexin type 9 (PCSK9)), Microsomal triglyceride transfer protein (MTP or ABL), chylomicron retention disease (CMRD), Secretion associated, Ras related GTPase (SARA2 gene), as well as 6 additional candidate genes in cholesterol metabolism (low density lipoprotein receptor (LDLR), Sortilin (SORT1), Inducible Degrader of the LDL receptor (IDOL), Cholesteryl ester transfer protein (CETP), Apolipoprotein E (ApoE) and Angiopoietin-like Protein 3 (ANGTPL3)). All the recruited index cases (n=200) will be genotyped to select only those without mutations in previously described genes, being approximately 50% of our index case cohort. Step-2. Identification of informative families and exome sequencing In patients without identified mutations, the investigators will conduct a familial screening in order to identify other cases of FHBL among proband relatives. An analysis of fasting plasma lipid parameters (total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Low-Density Lipoproteins (LDL-C) and triglycerides (TG)) will be performed for each related. Affected subjects will be determined by a spontaneous LDL-C \< 80 mg/dl and/or apoB \< 50 mg/dl. In contrast, non-affected subjects will display LDL-C \> 80 mg/dl and/or apoB \> 50 mg/dl. For large families, the investigators will then combine whole-exome sequencing and linkage analysis to identify any novel genetic variant likely explaining FHBL. Depending on family pedigree, whole-exome sequencing (WES) will be performed on 2 to 5 patients per family. All relatives will be genotyped for linkage analysis. In parallel to this genetic approach, a regional epidemiological analysis will be performed to identify some geographical clusters with a high prevalence of the disease, as developed in the project named VaCaRMe (for Vascular and Cardiac, Respiratory and Metabolic overcome diseases) An additional aim, based on an exhaustive phenotyping of FHBL patients, is to investigate the safety of very low LDL-C and to perform some genotype-phenotype correlations in patients with FHBL population." ### Conditions Module **Conditions:** - Hypobetalipoproteinemia **Keywords:** - Low LDL-C - Target Identification - Genetic - Endocrinology - Cardiovascular Disease ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 435 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Genetic: hypobetalipoproteinemia genetic and genotypic screening **Label:** genetic analysis **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - genetic analysis **Name:** hypobetalipoproteinemia genetic and genotypic screening **Type:** GENETIC ### Outcomes Module #### Other Outcomes **Description:** To determine number of phenotypes associated to genotype of FHBL and very low LDL-C. (Liver steatosis, Glucose homeostasis, Cancer, Depression scores, Cardiovascular diseases). **Measure:** number of phenotypes associated to genotype of FHBL and very low LDL-C **Time Frame:** ten years #### Primary Outcomes **Description:** To identify new gene involved in FHBL and determine genetic cause of FHBL (Patients with FHBL and their relatives will be recruited to establish familial forms of FHBL in large informative families with no mutations in known classical FHBL genes. This will allow perform genetic analysis using new approaches to genetic broadband (exome sequencing analysis + linkage analysis). This approach will allow specify which chromosomal regions are shared only by affected individuals, and identify new candidate genes). **Measure:** type and number of genetic abnormalities leading to FHBL **Time Frame:** ten years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * For index cases without family screening: o Patient with HBL: fasting LDL-C ≤ 50 mg/dl. * For familial affected cases: * Relative with HBL: fasting LDL-C ≤ 80 mg/dl and/or Apo B ≤ 50 mg/dl and at least one related family case suffering from HBL. All subjects, including familial non-affected cases, must give written consent (dated and signed) to participate at the constitution of biobank (including DNA samples and urine samples). Exclusion Criteria: * Use of lipid-lowering drugs (statins, fibrates, ezetimibe, bile-acid sequestering resin) or nutraceuticals known to affect lipids (red yeast rice, margarine and dairy with plant sterol) * Patient screened within an extreme metabolic disturbance (emergency situations, sepsis, hospitalization in intensive care unit) * Patients with hyperthyroidism, severe liver failure, end stage chronic kidney disease, serious pancreatic failure, anemia related to thalassemia or sickle cell disease, strict vegan diet or malnutrition * Refusal of the patient or his legal representative to participate in the study" **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Nantes **Country:** France **Facility:** CHU de Nantes **Zip:** 44093 #### Overall Officials **Official 1:** **Affiliation:** Health Care Centers of French Health Insurance in Saint-Nazaire **Name:** Charlotte AUTHIER, Doctor **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Health Care Centers of French Health Insurance in La Roche sur Yon **Name:** Didier GOXE **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007009 - Term: Hypolipoproteinemias - ID: D000008052 - Term: Lipid Metabolism, Inborn Errors - ID: D000008661 - Term: Metabolism, Inborn Errors - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000050171 - Term: Dyslipidemias - ID: D000052439 - Term: Lipid Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10045 - Name: Hypobetalipoproteinemias - Relevance: HIGH - As Found: Hypobetalipoproteinemia - ID: M10059 - Name: Hypolipoproteinemias - Relevance: LOW - As Found: Unknown - ID: M11641 - Name: Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M11054 - Name: Lipid Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - 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: T2225 - Name: Familial Hypobetalipoproteinemia - Relevance: HIGH - As Found: Hypobetalipoproteinemia - ID: T2942 - Name: Hypolipoproteinemia - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006995 - Term: Hypobetalipoproteinemias ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00578279 **Brief Title:** Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN)With Alcohol in Unresectable Pancreatic Cancer: a Pilot Study **Official Title:** Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN) With Alcohol in Patients With Locally Advanced and Unresectable Pancreatic Adenocarcinoma: A Randomized Pilot Study #### Organization Study ID Info **ID:** 0702-25 #### Organization **Class:** OTHER **Full Name:** Indiana University #### Secondary ID Infos **ID:** IRB # 0702-25 **ID:** Clarian Values Grant: vfr-262 ### Status Module #### Completion Date **Date:** 2009-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-10-19 **Type:** ESTIMATED **Last Update Submit Date:** 2012-09-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-06 **Type:** ACTUAL #### Results First Post Date **Date:** 2012-10-19 **Type:** ESTIMATED **Results First Submit Date:** 2010-09-23 **Results First Submit QC Date:** 2012-09-18 #### Start Date **Date:** 2007-03 **Status Verified Date:** 2010-06 #### Study First Post Date **Date:** 2007-12-21 **Type:** ESTIMATED **Study First Submit Date:** 2007-12-19 **Study First Submit QC Date:** 2007-12-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Indiana University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to obtain preliminary safety and efficacy data after endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with locally advanced or unresectable pancreatic adenocarcinoma. Hypotheses: 1. Increased amounts of alcohol used in EUS-CPN is safe and more efficacious in improving pain relief in patients with locally advanced or unresectable pancreatic adenocarcinoma. 2. Effective pain relief obtained from EUS-CPN will be related to better quality of life (QOL) ### Conditions Module **Conditions:** - Pancreatic Cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** subject randomized to 10ml of dehydrated alcohol **Intervention Names:** - Drug: dehydrated alcohol **Label:** A **Type:** OTHER #### Arm Group 2 **Description:** subject randomized to 20ml of dehydrated alcohol **Intervention Names:** - Drug: dehydrated alcohol **Label:** B **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - A - B **Description:** subject randomized to 10ml or 20ml of dehydrated alcohol one time during the EUS-CPN procedure **Name:** dehydrated alcohol **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Pain will be assessed at baseline 24 hours after the procedure and weekly thereafter, until the subject reports no subjective pain relief from the procedure. Pain relief is defined as a decrease in 2 points on a 0-10 point pain rating scale. Zero is no pain and 10 is the worst pain. **Measure:** The Change in Mean Pain Scale Rating in Patients Following Treatment With 10mL or 20mL of Alcohol Injection **Time Frame:** baseline up to 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * A total of 20 consecutive subjects with locally advanced or unresectable pancreatic adenocarcinoma (stage II to IV) with pain (abdominal and/or back). Subjects with known or suspected unresectable pancreatic adenocarcinoma will be recruited for this study, as a diagnosis of unresectable pancreatic adenocarcinoma is often made during the endoscopic ultrasound (EUS) procedure. * Subjects must have documented disease by computed tomography (CT), endoscopic retrograde cholangio-pancreatography (ERCP), or EUS. * Subjects undergoing EUS for pancreatic cancer staging. * Subjects undergoing pancreatic cancer surgery are eligible for study entry beginning 5 days after the operation if they have not had an intraoperative celiac plexus neurolysis. * No evidence of dementia or altered mental status that would prohibit the giving and understanding of informed consent, and no evidence of psychiatric risk that would preclude adequate compliance with this protocol. Subjects must not have a coagulopathy (platelet \<50,000, INR\>1.5, or bleeding disorder, or on blood thinners) Subjects with platelets below 50,000 will not be eligible to participate in this study due to the risk of bleeding. Patients will be asked to discontinue use of non-steroidals for 5 days prior to the procedure. Patients on plavix will be asked to discontinue use for 7 days prior to the procedure if they are clinically able to do so. Patients on coumadin or lovenox will also need to discontinue use prior to the procedure, but decisions regarding their management will be made on an individual basis as per our usual standards of care. * Subjects must provide signed written informed consent. * A baseline pain score is not required, however, subjects must be having pain that is requiring a stable dose of pain medication for control of pain. Exclusion Criteria: * Subjects will be excluded if they have undergone a celiac plexus neurolysis (endoscopic, percutaneous, or surgical). * Presence of an implanted epidural or intrathecal analgesic therapy. Subjects with psychiatric illness that affects their ability to assess quality of life or compliance with the protocol. * Subjects with uncorrectable coagulopathy * Subjects with an allergy to bupivacaine or alcohol. * Presence of an aneurysm in the abdominal aorta, celiac trunk, or superior mesenteric artery. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Indianapolis **Country:** United States **Facility:** Clarian Health: Indiana University Hospital **State:** Indiana **Zip:** 46202 #### Overall Officials **Official 1:** **Affiliation:** Indiana University **Name:** Julia LeBlanc, MD, MPH **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: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13110 - Name: Pancreatic Neoplasms - Relevance: HIGH - As Found: Pancreatic Cancer - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M5696 - Name: Celiac Disease - 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: 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 - Ancestors - ID: D000000891 - Term: Anti-Infective Agents, Local - ID: D000000890 - Term: Anti-Infective Agents - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M3777 - Name: Ethanol - Relevance: HIGH - As Found: Ureteral catheter - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M4215 - Name: Anti-Infective Agents, Local - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000000431 - Term: Ethanol ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** 10 mL of Alcohol Injection **Description:** subject randomized to 10ml of dehydrated alcohol **ID:** EG000 **Other Num at Risk:** 10 **Serious Number At Risk:** 10 **Title:** 10 mL of Alcohol Injection **Group ID:** EG001 **Title:** 20 mL of Alcohol Injection **Description:** subject randomized to 20ml of dehydrated alcohol **ID:** EG001 **Other Num at Risk:** 10 **Serious Number At Risk:** 10 **Title:** 20 mL of Alcohol Injection **Frequency Threshold:** 1 **Time Frame:** 12 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 10 **Group ID:** BG001 **Value:** 10 **Group ID:** BG002 **Value:** 20 **Units:** Participants ### Group **ID:** BG000 **Title:** 10 mL of Alcohol Injection **Description:** subject randomized to 10ml of dehydrated alcohol ### Group **ID:** BG001 **Title:** 20 mL of Alcohol Injection **Description:** subject randomized to 20ml of dehydrated alcohol ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 14 **Value:** 66 #### Measurement **Group ID:** BG001 **Spread:** 10 **Value:** 63 #### Measurement **Group ID:** BG002 **Spread:** 12 **Value:** 64 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 11 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 9 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 20 **Class Title:** United States **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:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Indiana University Medical Center **Phone:** (317) 948-8125 **Title:** Julia K. LeBlanc, MD ## Results Section - Outcome Measures Module ### Outcome Measure 1 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Anticipated Posting Date:** 2010-12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.8 - **Upper Limit:** - **Value:** 7.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9.2 - **Upper Limit:** - **Value:** 8.4 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Pain will be assessed at baseline 24 hours after the procedure and weekly thereafter, until the subject reports no subjective pain relief from the procedure. Pain relief is defined as a decrease in 2 points on a 0-10 point pain rating scale. Zero is no pain and 10 is the worst pain. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** baseline up to 1 year **Title:** The Change in Mean Pain Scale Rating in Patients Following Treatment With 10mL or 20mL of Alcohol Injection **Type:** PRIMARY **Unit of Measure:** units on a scale ##### Group **Description:** subject randomized to 10ml of dehydrated alcohol **ID:** OG000 **Title:** 10 mL of Alcohol Injection ##### Group **Description:** subject randomized to 20ml of dehydrated alcohol **ID:** OG001 **Title:** 20 mL of Alcohol Injection ### Participant Flow Module #### Group **Description:** subject randomized to 10ml of dehydrated alcohol **ID:** FG000 **Title:** 10 mL of Alcohol Injection #### Group **Description:** subject randomized to 20ml of dehydrated alcohol **ID:** FG001 **Title:** 20 mL of Alcohol Injection #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 10 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 10 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 10 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 10 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05139979 **Brief Title:** Yogic Breathing and Guided Meditation for Long Covid Symptoms **Official Title:** Yogic Breathing and Guided Meditation for Long Covid Symptoms #### Organization Study ID Info **ID:** 2021P000552 #### Organization **Class:** OTHER **Full Name:** Beth Israel Deaconess Medical Center ### Status Module #### Completion Date **Date:** 2024-03-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-14 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-13 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-03-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-09-15 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2021-12-01 **Type:** ACTUAL **Study First Submit Date:** 2021-09-23 **Study First Submit QC Date:** 2021-11-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Beth Israel Deaconess Medical Center #### Responsible Party **Investigator Affiliation:** Beth Israel Deaconess Medical Center **Investigator Full Name:** Balachundhar Subramaniam **Investigator Title:** Professor of Anesthesia **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study aims to assess the impact of brief digitally delivered breathing practice and guided meditation on post-Covid physical and mental symptoms in Long Covid Patients. **Detailed Description:** Long Covid symptoms can last weeks to months after the initial Covid infection or can appear weeks after. It can occur in those with mild disease or asymptomatic patients. Most commonly reported symptoms of Long Covid are: * Tiredness or fatigue * Difficulty thinking or concentrating (sometimes referred to as "brain fog") * Headache * Loss of smell or taste * Dizziness on standing * Fast-beating or pounding heart (also known as heart palpitations) * Chest pain * Difficulty breathing or shortness of breath * Cough * Joint or muscle pain * Depression or anxiety * Fever * Symptoms that get worse after physical or mental activities To this date, nearly 180 million people have been infected with Covid19 and over 3 million have lost their lives worldwide. The increasing prevalence of patients with Long Covid symptoms and the lack of effective solutions to address their condition, creates an urgent need for non-pharmacological interventions that are effective and scalable and can be delivered online to accommodate for the limitations due to the Covid pandemic. Yogic Breathing and Meditation techniques have been shown to have various health benefits including improving pulmonary function and mental health. Prominent health institutions are recommending breathing exercise to their Covid patients to assist their respiratory recovery9. Meditation and breathing is also shown to help with Covid related stress and anxiety. This study is a waitlisted randomized controlled trial conducted in 2 phases: Phase 1: If participants are in the intervention group, they will be asked to learn and practices two Yogic Breathing practices (Simha Kriya and Nadi Shuddhi) and a guided meditation (Isha Kriya) for 3 weeks They will be asked to complete a set of questionnaires at baseline and the end of each week. Participants in the waitlisted control group will be asked to perform their regular daily routine as they wait to be enrolled into the intervention at the end of 3 weeks. The waitlisted control group will also be recruited for semi-structured individual interviews during this time. Phase 2: The waitlisted control group will begin the intervention at week 3 and continue until week 6. They will be asked to continue completing the questionnaires at the end of each week. The intervention group will be asked to complete a final follow-up questionnaire at the end of week 6. The intervention group will also be recruited for semi-structured individual interviews during this time. Focus group discussions with both the intervention and control groups are conducted at the end of the study to collect general information about the participant's general experience with the current study and what matters to them as a Long COVID patients. ### Conditions Module **Conditions:** - COVID-19 - Stress - Shortness of Breath **Keywords:** - Long COVID-19 - Mental health - Anxiety - Stress - Breathing - Meditation - Yoga - Isha Kriya ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Upon enrollment and randomization, the intervention group will be followed weekly for 3 weeks as well as on week 6. The waitlisted control group will be followed for 3 weeks as controls and will then learn the intervention and be followed for additional 3 weeks (total of 6 weeks). ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 189 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Breathing and Wellness Webinar: two yogic breathing practices (Simha Kriya and Naddi Shuddi) and a guided meditation (Isha Kriya). **Intervention Names:** - Behavioral: Breathing and Wellness Webinar **Label:** Webinar-Based Intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** This group will be asked to wait for 3 weeks before being introduced to the Breathing and Wellness Webinar intervention which includes two yogic breathing practices (Simha Kriya and Naddi Shuddi) and a guided meditation (Isha Kriya). **Intervention Names:** - Other: Routine Daily Activity **Label:** Control **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Webinar-Based Intervention **Description:** Simha Kriya : a 3-minute energizing breathing practice to expand lung capacity and improve immunity, to be practiced twice daily. Nadi Shuddhi - a gentle 4-minute breathing practice for creating mental balance and relaxation, to be practiced for a minimum of 4 minutes daily. Isha Kriya - a 15-minute guided meditation that incorporates the breath and the awareness to create mental clarity and health, to be practiced at least once (ideally twice) daily. **Name:** Breathing and Wellness Webinar **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Control **Description:** Participants in the control group are asked to perform routine daily activities until enrolled into the intervention arm. **Name:** Routine Daily Activity **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The weekly compliance questionnaire is a tool which helps the participants to keep track of their activities each week. This enables the study team to measure compliance and protocol adherence by the participants by collecting information on their routine activity practiced and its frequency. This will be reported in "Number of days an intervention was practiced in a week". Participants completing at least 3 days of activity would be considered as compliant for that week. **Measure:** Compliance **Time Frame:** For Phase 1 analysis: Baseline to 3 weeks. For Phase 2 analysis: Baseline to 6 weeks. #### Secondary Outcomes **Description:** PSS is a 10-question validated instrument that assesses stress. Participants are asked to rate on a scale of 0 (never) to 4 (very often) how often they agree with various statements. **Measure:** Perceived Stress Scale (PSS) **Time Frame:** For Phase 1 analysis: Baseline to 3 weeks. For Phase 2 analysis: Baseline to 6 weeks. **Description:** This is a short validated survey used to measure six different dimensions of mood swings over a period of time. These include: Tension or Anxiety, Anger or Hostility, Vigor or Activity, Fatigue or Inertia, Depression or Dejection, Confusion or Bewilderment. A five-point scale ranging from "not at all" to "extremely" is administered and scores for each dimension contributes to calculation of positive and negative subscales in conjunction to total mood disturbance. **Measure:** Profile of Mood States (POMS) **Time Frame:** For Phase 1 analysis: Baseline to 3 weeks. For Phase 2 analysis: Baseline to 6 weeks. **Description:** SF12 is a validated self-reported measure of the impact of health on everyday quality of life. It evaluates domains of physical activities, social activities, usual role activities, bodily pain, general mental health, vitality and general health perception. **Measure:** Quality of Life Survey (SF12) **Time Frame:** For Phase 1 analysis: Baseline to 3 weeks. For Phase 2 analysis: Baseline to 6 weeks. **Description:** MDP is a validated scale to assess the overall breathing discomfort, sensory qualities and emotional responses using 8 questions. It is not intended for a particular activity and can be used during rest, activity or during clinical care. For assessing Long Covid patients, the first three parts (breathing discomfort and sensory qualities) are commonly used. **Measure:** Multidimensional Dyspnea Profile (MDP) **Time Frame:** For Phase 1 analysis: Baseline to 3 weeks. For Phase 2 analysis: Baseline to 6 weeks. **Description:** SS8 is a validated brief questionnaire to assess common somatic symptoms including pain, shortness of breath, dizziness, fatigue and trouble sleeping. Participants are asked to rate on a scale of 0 (not at all) to 4 (very much) how often they agree with various statements. Items from each of the 8 questions are then summed to create a total perceived stress score. **Measure:** Somatic Symptom Scale 8 Items (SS8) **Time Frame:** For Phase 1 analysis: Baseline to 3 weeks. For Phase 2 analysis: Baseline to 6 weeks. **Description:** The semi-structured individual interviews will allow us to gain rich, descriptive information about the participant's experience with the long COVID symptoms, treating physicians, and the effect of the provided practices on their symptoms. The focus group interviews will be semi-structured to ensure a systematic and flexible approach to data collection, allowing us to gain rich information about the participant's general experience with the current study and what matters to them as a Long COVID patients. The interviews will cover the following main topics: (1) Perceptions of the participants on their long COVID symptoms, (2) Perceptions of the participants on their treating physicians (3) the effect of the provided meditation practices on their long COVID symptoms (4) and what matters to the Long COVID patients as well as their general experience as participants in the current study. **Measure:** Qualitative Assessments **Time Frame:** For Phase 1 analysis: Baseline to 3 weeks. For Phase 2 analysis: Baseline to 6 weeks. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age between 18 and 70 years * Interested in attending the online Breathing and Wellness webinar. * Laboratory-confirmed (PCR) history of Covid-19 infection. * Long Covid condition diagnosis by a physician. * Able to read and comprehend English. * Currently residing in the United States. Exclusion Criteria: ● Any medically limiting diagnosis that prevents a patient from doing the intervention or completing the assessments as determined by the PI such as severe Major Depression (under medication), Schizophrenia, Bipolar disorder. **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Beth Israel Deaconess Medical Centre **State:** Massachusetts **Zip:** 02215 #### Overall Officials **Official 1:** **Affiliation:** Beth Israel Deaconess Medical Center **Name:** Balachundar Subramaniam, MD, MPH **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Greenhalgh T, Knight M, A'Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020 Aug 11;370:m3026. doi: 10.1136/bmj.m3026. No abstract available. **PMID:** 32784198 **Citation:** Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021 May;8(5):416-427. doi: 10.1016/S2215-0366(21)00084-5. Epub 2021 Apr 6. **PMID:** 33836148 **Citation:** Abel AN, Lloyd LK, Williams JS. The effects of regular yoga practice on pulmonary function in healthy individuals: a literature review. J Altern Complement Med. 2013 Mar;19(3):185-90. doi: 10.1089/acm.2011.0516. Epub 2012 Sep 14. **PMID:** 22978245 **Citation:** Budhi RB, Payghan S, Deepeshwar S. Changes in Lung Function Measures Following Bhastrika Pranayama (Bellows Breath) and Running in Healthy Individuals. Int J Yoga. 2019 Sep-Dec;12(3):233-239. doi: 10.4103/ijoy.IJOY_43_18. **PMID:** 31543632 **Citation:** Rangasamy V, Thampi Susheela A, Mueller A, F H Chang T, Sadhasivam S, Subramaniam B. The effect of a one-time 15-minute guided meditation (Isha Kriya) on stress and mood disturbances among operating room professionals: a prospective interventional pilot study. F1000Res. 2019 Mar 26;8:335. doi: 10.12688/f1000research.18446.1. eCollection 2019. **PMID:** 32665843 **Citation:** Maric V, Mishra J, Ramanathan DS. Using Mind-Body Medicine to Reduce the Long-Term Health Impacts of COVID-Specific Chronic Stress. Front Psychiatry. 2021 Feb 22;12:585952. doi: 10.3389/fpsyt.2021.585952. eCollection 2021. No abstract available. **PMID:** 33692706 **Citation:** Rain M, Subramaniam B, Avti P, Mahajan P, Anand A. Can Yogic Breathing Techniques Like Simha Kriya and Isha Kriya Regulate COVID-19-Related Stress? Front Psychol. 2021 Apr 15;12:635816. doi: 10.3389/fpsyg.2021.635816. eCollection 2021. **PMID:** 33935886 **Citation:** Narayanan S, Tennison J, Cohen L, Urso C, Subramaniam B, Bruera E. Yoga-Based Breathing Techniques for Health Care Workers During COVID-19 Pandemic: Interests, Feasibility, and Acceptance. J Altern Complement Med. 2021 Aug;27(8):706-709. doi: 10.1089/acm.2020.0536. Epub 2021 Apr 9. **PMID:** 33835830 #### See Also Links **Label:** Related Info **URL:** http://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-long-term-effects/art-20490351 **Label:** Related Info **URL:** http://covid19.who.int **Label:** Related Info **URL:** http://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/coronavirus-recovery-breathing-exercises ## 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 - ID: D000012120 - Term: Respiration Disorders - ID: D000010335 - Term: Pathologic Processes - ID: D000094025 - Term: Post-Infectious Disorders - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000012818 - Term: Signs and Symptoms, Respiratory ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - ID: M3013 - Name: Post-Acute COVID-19 Syndrome - Relevance: HIGH - As Found: Long COVID - ID: M27137 - Name: Respiratory Aspiration - Relevance: LOW - As Found: Unknown - ID: M7591 - Name: Dyspnea - Relevance: HIGH - As Found: Shortness of Breath - ID: M16355 - Name: Syndrome - 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: 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 - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: M3014 - Name: Post-Infectious Disorders - 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: M15623 - Name: Signs and Symptoms, Respiratory - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 - ID: D000094024 - Term: Post-Acute COVID-19 Syndrome - ID: D000004417 - Term: Dyspnea ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05403879 **Brief Title:** Modified Hook Wiring Technique for Greater Tuberosity Fractures, a Prospective Study **Official Title:** Modified Hook Wiring Technique for Greater Tuberosity Fractures, a Prospective Study #### Organization Study ID Info **ID:** R.22.03.1644 #### Organization **Class:** OTHER **Full Name:** Mansoura University ### Status Module #### Completion Date **Date:** 2023-12-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-03 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-12-30 **Type:** ACTUAL #### Start Date **Date:** 2022-03-23 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2022-06-03 **Type:** ACTUAL **Study First Submit Date:** 2022-05-31 **Study First Submit QC Date:** 2022-05-31 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Mansoura University #### Responsible Party **Investigator Affiliation:** Mansoura University **Investigator Full Name:** Amr Elshahhat, MD. **Investigator Title:** lecturer of orthopedics **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False ### Description Module **Brief Summary:** the purpose of this study is to assess functional and radiological outcome of open reduction and internal fixation of isolated displaced greater tuberosity fractures (more than 5mm displacement) in adults advocating modified hook wiring with a follow-up period of one year. **Detailed Description:** after being informed about the study and potential risks, all enrolled cases giving informed consent will undergo fixation of their fractured greater tuberosity, then physiotherapy. patients will be followed up till full union, clinical and radiological follow up for at least one year utilizing approved clinical scores and radiological criteria for healing. any complication will be recorded. ### Conditions Module **Conditions:** - Greater Tuberosity Fractures ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 10 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: fixation of greater tuberosity fractures **Label:** cases undergoing fixation of fractured greater tuberosity **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - cases undergoing fixation of fractured greater tuberosity **Description:** deltopectoral approach for shoulder, then open reduction and fixation of displaced greater tuberosity fractures using hooked Kirshner wires **Name:** fixation of greater tuberosity fractures **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** postoperative assessing pain, range of motion, function of shoulder. Scores range from 0 to 100 with a score of 0 indicating a worse shoulder condition and 100 indicating a better shoulder condition **Measure:** functional outcome using American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment score **Time Frame:** at least one year follow up #### Secondary Outcomes **Description:** estimate time till radiological healing on follow-up radiographs **Measure:** healing time **Time Frame:** anticipated 2-4 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Patients presented and admitted at Mansoura Trauma, emergency hospital affiliated to Mansoura university, with acute isolated displaced GT fractures ( more than 5mm displacement), with/without glenohumeral dislocations, with age between 18years to 50 years. Exclusion Criteria: 1. Skeletally immature patients (less than 18 years), age more than 50 years. 2. Open and pathological fractures 3. Associated proximal humeral fractures 4. History of previous GH dislocations 5. History of previous shoulder injuries or surgeries **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Mansoura **Country:** Egypt **Facility:** Mansoura university hospital **State:** Dakahlia **Zip:** 35511 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014947 - Term: Wounds and Injuries - ID: D000070599 - Term: Shoulder 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: M15592 - Name: Shoulder Fractures - Relevance: HIGH - As Found: Greater Tuberosity Fractures - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M602 - Name: Shoulder Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000050723 - Term: Fractures, Bone - ID: D000012784 - Term: Shoulder Fractures ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03404479 **Acronym:** DIA IIT_01 **Brief Title:** Trial to Evaluate Efficacy and Safety of Combination of Diacerein and Celecoxib Administered in Patients With Knee OA **Official Title:** A Prospective, Randomized, Double-blinded, Multi-center, Trial to Evaluate Efficacy and Safety of Combination of Diacerein and Celecoxib Administered Orally in Patients With Knee Osteoarthritis #### Organization Study ID Info **ID:** DIA IIT_01 #### Organization **Class:** OTHER **Full Name:** Seoul St. Mary's Hospital ### Status Module #### Completion Date **Date:** 2019-01-02 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2018-02-26 **Type:** ACTUAL **Last Update Submit Date:** 2018-02-22 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-01-02 **Type:** ESTIMATED #### Start Date **Date:** 2018-01-25 **Type:** ACTUAL **Status Verified Date:** 2018-02 #### Study First Post Date **Date:** 2018-01-19 **Type:** ACTUAL **Study First Submit Date:** 2018-01-12 **Study First Submit QC Date:** 2018-01-12 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Korea University Guro Hospital #### Lead Sponsor **Class:** OTHER **Name:** Whan-Seok Choi #### Responsible Party **Investigator Affiliation:** Seoul St. Mary's Hospital **Investigator Full Name:** Whan-Seok Choi **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:** The purpose of this study is to evaluate the pain relief effect of Co-administration of Diacerein with Celecoxib in patients with knee osteoarthritis compared with single administration of each drug. **Detailed Description:** A large epidemiological study in Europe reported that over four-thirds of patients with osteoarthritis received combination therapy with two or more drugs. Approximately 1.5% of patients with osteoarthritis using three or more drugs are using COX-2(Cyclo-oxygenase-2) inhibitors and SYSADOA(Symptomatic slow acting drug), And it has been investigated that much more patients are using the two classes of drugs when the range is extended to other oral NSAIDs other than COX-2 inhibitors. Therefore, considering the characteristics of patients with osteoarthritis, such as basal disease and treatment effects on each type of drug, it is important to find the optimal combination of drugs for each patient characteristics. There is a previous study using osteoarthritis rat model as a biological basis of diacerein and celecoxib administration. Previous studies have shown that the combined use of Diacerein and Celecoxib improves osteoarthritis. The purpose of this study is to evaluate the pain relief effect of Co-administration of Diacerein with Celecoxib in patients with knee osteoarthritis compared with single administration of each drug. ### Conditions Module **Conditions:** - Knee Osteoarthritis **Keywords:** - Knee Osteoarthritis - Diacerein ### 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:** 90 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Co-administration of Diacerein 50mg, Celecoxib 100mg. **Intervention Names:** - Drug: Diacerein - Drug: Celecoxib **Label:** Co-administration group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Single administration of Diacerein 50mg and placebo. **Intervention Names:** - Drug: Diacerein **Label:** Single administration group 1 **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Single administration of Celecoxib 100mg and placebo. **Intervention Names:** - Drug: Celecoxib **Label:** Single administration group 2 **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Co-administration group - Single administration group 1 **Description:** For 12 weeks, administered twice a day by oral. **Name:** Diacerein **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Co-administration group - Single administration group 2 **Description:** For 12 weeks, administered twice a day by oral. **Name:** Celecoxib **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Changes in pain VAS(Visual analogue scale) score before and after 12 weeks of drugs administration. (No pain score: 0, Worst pain score: 100) **Measure:** pain VAS score **Time Frame:** 12 weeks after randomization #### Secondary Outcomes **Description:** Changes in pain NRS(Numeric rating scale) score before and after 12 weeks of drugs administration. (No pain score: 0, Worst pain score: 10) **Measure:** pain NRS score **Time Frame:** 12 weeks after randomization **Description:** Changes in WOMAC(Western Ontario and mcmaster Universities Osteoarthritis Index) index score before and after 12 weeks of drugs administration (possible score range, Pain: 0-20, Stiffness: 0-8, Physical function: 0-68; Total Score range: 0-96 ('none' to 'extreme')) **Measure:** WOMAC index score **Time Frame:** 12 weeks after randomization **Description:** Changes in GSRS(Gastrointestinal symptom rating scale) index score before and after 12 weeks of drugs administration. (Score range: 0-45 ('none' to 'extreme')) **Measure:** GSRS index score **Time Frame:** 12 weeks after randomization ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Subjects who voluntarily consented, after listening enough explanation for this study and investigational product. 2. Adult over 50 years of age. 3. At least one of the knee pain VAS score is 40mm or more. 4. Meets the ACR(American College of Rheumatology) criteria for diagnosis. (1) Confirmation of osteophytes on radiographic inspection. (2) One or more of the following three items. ① Age\> 50 years ② Morning stiffness \<30 minutes ③ Crepitus 5. Patients who require medication for more than 12 weeks due to osteoarthritis symptoms. 6. Those who are able to follow the requirements of this clinical trial, such as being able to trace during the clinical trial period and to read and write the VAS questionnaire. 7. Those who weigh more than 40kg Exclusion Criteria: 1. Secondary knee osteoarthritis 2. Other inflammatory Knee Osteoarthritis (e.g. gout, rheumatoid arthritis, etc.) 3. Patients presenting with gastroesophageal reflux disease, peptic ulcer. 4. Helicobacter infected patients who have not been treated for eradication (recruitment if negative in re-examination after treatment). 5. Short bowel syndrome that can cause inflammatory bowel disease (ulcerative colitis, Crohn's disease) and drug absorption disorder. 6. Intestinal obstruction syndrome 7. Unexplained abdominal pain 8. ALT(Alanine aminotransferase) level of liver function test exceeded 5 times of reference range 9. Total bilirubin level exceeded 2 mg / dL 10. Serum albumin level less than 2 g / dL 11. Ascites 12. Hepatic encephalopathy 13. Hepatitis B, hepatitis C (excluding healthy carriers) or HIV positive 14. MDRD(Modification of Diet in Renal Disease) Estimated Glomerular filtration rate less than 60 mL / m2 15. Patients with hyperkalemia (over 5.5 meq / L) 16. history of asthma, acute rhinitis, nasal polyps, angioedema, urticaria or allergic reactions to aspirin or other non-steroidal anti-inflammatory drugs(including COX-2 inhibitors). 17. Malignant tumors other than basal cell or squamous cell carcinoma of the skin, CIN(Cervical Intraepitherial Neoplasia) and CIS(Carcinoma in situ) of the cervix, and intraepithelial carcinoma of other areas Within 5 years of consent date. 18. Medical history of hypersensitivity to the components of the investigational products. (The components of test drug 1 and 2, including the Rhein-based drug) 19. Patients with an allergic reaction to sulfonamide. 20. Patients with galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption. 21. Subjects who have not reached the prescribed period after receiving contraindicated medication or treatment before participation in this clinical trial. 22. Patients receiving contraindicated medication. 23. Alcohol and other drug abuse cases based on 6 months before screening. 24. Pregnant women or nursing mothers who are not willing to stop breastfeeding. 25. Female who do not fall into one or more of the following categories(In other words, only the following female can participate:) * (1) Menopause (non-therapy-induced amenorrhea of more than 12 months) Female * (2) Female infertility due to surgery (no ovaries and / or uterus) * (3) If you have sexual intercourse with only one male partner who has been confirmed to have no semen after fertilization. * (4) Female subjects who agreed to abstinence during the clinical trial period. * If the subject is assured of an abstinence throughout the trial period.(e.g. clergy) * However, intermittent abstinence (eg, contraception using ovulation period, symptothermal) or coitus interrupts is not a case of consent for abstinence. * (5) For women of childbearing age, the following methods or methods of contraception use the effective method of contraception to be used during the period of this clinical trial: * Oral contraceptive * The contraceptive patch * Intra uterine device (IUD) * contraceptive implant * contraceptive injection * intrauterine hormonal apparatus * Tubal ligation and infertility surgery 26. If 30 days have not elapsed after the date of signing of the previous clinical trial or currently participating in other clinical trials. 27. Patients who are scheduled for surgery during the clinical trial period or who have difficulties in completing the protocol during this clinical trial due to other reasons. 28. In addition to the above, other diseases that the investigator judges to be inappropriate. **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Yu-na Jo **Phone:** 82-70-4335-5448 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Sung Woon Yang **Phone:** 82-31-354-0604 **Role:** CONTACT #### Locations **Location 1:** **City:** Seoul **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Whan-Seok Choi, M.D., Ph.D. - **Phone:** 82-2-2258-6285 - **Role:** CONTACT ***Contact 2:*** - **Name:** Whan-Seok Choi, M.D., Ph.D - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Chul-Min Kim, M.D., Ph.D - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Ji Hyeon Ju, M.D., Ph.D - **Role:** SUB_INVESTIGATOR **Country:** Korea, Republic of **Facility:** Seoul ST. Mary's Hospital **Status:** RECRUITING **Zip:** 06591 **Location 2:** **City:** Seoul **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Seon-Mee Kim, MD, PhD - **Phone:** 82-2-2626-3276 - **Role:** CONTACT ***Contact 2:*** - **Name:** Seon-Mee Kim, M.D., Ph.D. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Korea, Republic of **Facility:** Korea University Guro Hospital **Status:** RECRUITING **Zip:** 08308 #### Overall Officials **Official 1:** **Affiliation:** Seoul St. Mary's Hospital **Name:** Whan-Seok Choi, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Korea University Guro Hospital **Name:** Seon-Mee Kim, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Li Z, Meng D, Li G, Xu J, Tian K, Li Y. Celecoxib Combined with Diacerein Effectively Alleviates Osteoarthritis in Rats via Regulating JNK and p38MAPK Signaling Pathways. Inflammation. 2015 Aug;38(4):1563-72. doi: 10.1007/s10753-015-0131-3. **PMID:** 25687638 **Citation:** Martel-Pelletier J, Pelletier JP. Effects of diacerein at the molecular level in the osteoarthritis disease process. Ther Adv Musculoskelet Dis. 2010 Apr;2(2):95-104. doi: 10.1177/1759720X09359104. **PMID:** 22870441 **Citation:** Panova E, Jones G. Benefit-risk assessment of diacerein in the treatment of osteoarthritis. Drug Saf. 2015 Mar;38(3):245-52. doi: 10.1007/s40264-015-0266-z. **PMID:** 25652235 **Citation:** Nicolas P, Tod M, Padoin C, Petitjean O. Clinical pharmacokinetics of diacerein. Clin Pharmacokinet. 1998 Nov;35(5):347-59. doi: 10.2165/00003088-199835050-00002. **PMID:** 9839088 ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2023-05-09 - Date Unknown: Unknown #### Event: RESET - Date: 2024-01-23 - Date Unknown: Unknown ## 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: HIGH - As Found: Knee Osteoarthritis - 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: 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: M241175 - Name: Diacerein - Relevance: HIGH - As Found: Adenotonsillectomy - 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 - ID: C000025292 - Term: Diacerein ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2023-05-09 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2023-05-09 - Reset Date: 2024-01-23 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06283979 **Acronym:** BLADE OPU2 **Brief Title:** A Randomized Controlled Phase II Trial of STIMULAN VG vs Standard of Care (SoC) for the Treatment of Osteomyelitis Associated With Stage IV Pressure Ulcers. **Official Title:** A Multi-center, Randomized (1:1), Controlled Phase II Trial of STIMULAN VG With Debridement and a Course of Systemic Antibiotics vs Standard of Care (SoC) for the Treatment of Osteomyelitis Associated With Stage IV Pressure Ulcers. #### Organization Study ID Info **ID:** 199723 #### Organization **Class:** INDUSTRY **Full Name:** Biocomposites Ltd ### Status Module #### Completion Date **Date:** 2025-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-22 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-12-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-07-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-02-28 **Type:** ACTUAL **Study First Submit Date:** 2024-02-21 **Study First Submit QC Date:** 2024-02-21 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** MCRA #### Lead Sponsor **Class:** INDUSTRY **Name:** Biocomposites Ltd #### 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 trial is to assess the safety, tolerability and between-group effect size of STIMULAN VG (with debridement) and a course of systemic antibiotics to standard of care (debridement and systemic antibiotics only) for the treatment of osteomyelitis associated stage IV pressure ulcers. **Detailed Description:** The trial is an open-label, multi-center, randomized (1:1), controlled phase 2 trial in patients diagnosed with stage IV pressure ulcers. ### Conditions Module **Conditions:** - Pressure Ulcer, Stage IV - Osteomyelitis **Keywords:** - between-group effect size - surgical debridement - ulcer bursectomy - systemic antibiotics ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Ulcer bursectomy and debridement and STIMULAN VG insertion into the ulcer cavity. Flap closure. Peri-operative antibiotics. **Intervention Names:** - Combination Product: STIMULAN VG - Procedure: Standard of Care **Label:** Interventional STIMULAN VG **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Ulcer bursectomy, debridement and flap closure. Peri-operative antibiotics. **Intervention Names:** - Procedure: Standard of Care **Label:** Standard of Care (SoC) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Interventional STIMULAN VG **Description:** Insertion of STIMULAN VG into the ulcer cavity prior to flap closure. **Name:** STIMULAN VG **Type:** COMBINATION_PRODUCT #### Intervention 2 **Arm Group Labels:** - Interventional STIMULAN VG - Standard of Care (SoC) **Description:** Standard of Care. Ulcer bursectomy, debridement and flap closure. Peri-operative antibiotics. **Name:** Standard of Care **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** An individual patient treatment will be considered a success if there is complete wound closure and healing at the surgical site at two consecutive visits 2 weeks apart. **Measure:** Individual patient success and findings at the 8 week follow-up visit **Time Frame:** 8 week ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: In order to be eligible to participate in this study, subjects must meet all of the following criteria: 1. Presenting with a Stage IV pressure ulcers requiring treatment of excision, bony debridement and flap coverage. 2. Operative candidate for flap surgery. 3. Presence of focal osteomyelitis as suggested by imaging to show extent of infection. Acceptable imaging techniques are Magnetic Resonance Imaging or CT scan. 4. Adults ≥ 18 years in age at the time of treatment. 5. Psychosocially, mentally, and physically able to fully comply with this protocol, including adhering to scheduled visits, treatment plan, completing forms, and other study procedures. 6. Ability of the subject or legal authorized representative to provide voluntary, signed and dated informed consent prior to any study-related procedures. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from participating in this study: 1. Reasons contributing to pressure ulcer cannot be addressed. 2. Patients receiving primary closure 3. Severe immunological compromised patients as determined by the clinician. 4. Patients with diffuse or widespread pelvic osteomyelitis that is not amenable to adequate margins for debridement. 5. Current or recent history (within last 2 years) of active substance abuse (e.g., recreational drugs, narcotics, or alcohol) that in the judgement of the investigator, may compromise the participant's safety/recovery or ability to follow the trial procedures. 6. Current smoker. 7. Diabetic patient with Hba1C level above 9. 8. Allergy to any component of the investigational product, such as calcium sulfate, glycopeptide antibiotics (Vancomycin), or aminoglycoside antibiotics (Gentamicin). 9. Concurrent involvement in a study of another investigational product. 10. Pregnant or planning to become pregnant during study period. 11. Flexion contractures where patient cannot passively get full extension. 12. Uncontrolled muscle spasms. 13. Unable to comply with bedrest restriction. 14. Unable to provide consent. 15. Fecal or urinary incontinence with contamination of the wound. 16. Unable to achieve wheelchair and cushion offloading of pressure wound prior to surgery - as demonstrated by pressure mapping. 17. Investigator considers the participant to be clinically malnourished. 18. Any conditions with known hypercalcemia (\> 10.3 mg/dl) or posing a significant risk for developing hypercalcemia (i.e., Hyperparathyroidism). 19. Investigator believes trial participation may compromise safety of the participant or trial results. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Keira Watts, Clinical Project Manager **Phone:** +44 (0) 1782 338 580 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Nicole Villagomez **Phone:** (202) 552-5800 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000012883 - Term: Skin Ulcer - ID: D000012871 - Term: Skin Diseases - ID: D000001850 - Term: Bone Diseases, Infectious - ID: D000007239 - Term: Infections - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC01 - Name: Infections - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M6870 - Name: Pressure Ulcer - Relevance: HIGH - As Found: Pressure Ulcer - ID: M17206 - Name: Ulcer - Relevance: HIGH - As Found: Ulcer - ID: M12942 - Name: Osteomyelitis - Relevance: HIGH - As Found: Osteomyelitis - ID: M15686 - Name: Skin Ulcer - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin 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: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M5129 - Name: Bone Diseases, Infectious - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: T4321 - Name: Osteomyelitis - Relevance: HIGH - As Found: Osteomyelitis ### Condition Browse Module - Meshes - ID: D000010019 - Term: Osteomyelitis - ID: D000003668 - Term: Pressure Ulcer - ID: D000014456 - Term: Ulcer ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - 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:** NCT04939779 **Brief Title:** Trial to Evaluate Bioequivalence of LCB01-0371 in Different Batches **Official Title:** A Randomized, Open-label, Single-dose, Two-way Crossover, Phase 1 Trial to Evaluate Bioequivalence of "LCB01-0371(Batch#1650006)" and "LCB01-0371(Batch#3183817R)" in Healthy Adult Subjects #### Organization Study ID Info **ID:** LCB01-0371-18-1-08 #### Organization **Class:** INDUSTRY **Full Name:** LigaChem Biosciences, Inc. ### Status Module #### Completion Date **Date:** 2021-02-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-06-25 **Type:** ACTUAL **Last Update Submit Date:** 2021-06-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-01-24 **Type:** ACTUAL #### Start Date **Date:** 2021-01-14 **Type:** ACTUAL **Status Verified Date:** 2021-06 #### Study First Post Date **Date:** 2021-06-25 **Type:** ACTUAL **Study First Submit Date:** 2021-02-21 **Study First Submit QC Date:** 2021-06-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** LigaChem Biosciences, Inc. #### 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 objective of this clinical trial is to evaluate bioequivalence of "LCB01-0371 (Batch# 1650006)" and "LCB01-0371(Batch#3183817R) in healthy adult subject ### Conditions Module **Conditions:** - Healthy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 25 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Period 1: LCB01-0371 tablet 400mg (Reference drug, Batch# 1650006) Period 2: LCB01-0371 tablet 400mg (Test drug, Batch# 3183817R) **Intervention Names:** - Drug: LCB01-0371 tablet 400mg (Test drug, Batch# 3183817R) - Drug: LCB01-0371 tablet 400mg (Reference drug, Batch# 1650006) **Label:** Group A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Period 1: LCB01-0371 tablet 400mg (Test drug, Batch# 3183817R) Period 2: LCB01-0371 tablet 400mg (Reference drug, Batch# 1650006) **Intervention Names:** - Drug: LCB01-0371 tablet 400mg (Test drug, Batch# 3183817R) - Drug: LCB01-0371 tablet 400mg (Reference drug, Batch# 1650006) **Label:** Group B **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Group A - Group B **Description:** Oral administration **Name:** LCB01-0371 tablet 400mg (Test drug, Batch# 3183817R) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Group A - Group B **Description:** Oral administration **Name:** LCB01-0371 tablet 400mg (Reference drug, Batch# 1650006) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Pharmacokinetic parameters will be assessed using non-compartmental method **Measure:** Pharmacokinetic evaluation: The observed maximum concentration(Cmax) **Time Frame:** 0-12hours **Description:** Area under the plasma concentration curve from zero until the last measurable concentration **Measure:** Pharmacokinetic evaluation:Area under the blood concentration-time curve (AUClast) **Time Frame:** 0-12hours #### Secondary Outcomes **Description:** Pharmacokinetic parameters will be assessed using non-compartmental method **Measure:** Pharmacokinetic evaluation: Time to reach Cmax(Tmax) **Time Frame:** 0-12hours **Description:** Pharmacokinetic parameters will be assessed using non-compartmental method **Measure:** Pharmacokinetic evaluation: Elimination half-life(t1/2) **Time Frame:** 0-12hours **Description:** Pharmacokinetic parameters will be assessed using non-compartmental method **Measure:** Pharmacokinetic evaluation: Apparent total body clearance after extravascular administration(CL/F) **Time Frame:** 0-12hours **Description:** Pharmacokinetic parameters will be assessed using non-compartmental method **Measure:** Pharmacokinetic evaluation:Apparent volume of distribution after extravascular administration(Vd/F) **Time Frame:** 0-12hours **Description:** Area under the curve from time 0 extrapolated to infinite time **Measure:** Pharmacokinetic evaluation:Area under the blood concentration-time curve (AUCinf) **Time Frame:** 0-12hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. A person who is a healthy adult aged between 19 and 45 years old with the result of BMI between 18.0 kg/m2 and 28.0 kg/m2 2. A healthy adult whose weight is over 50 kg 3. A person who is deemed suitable for a clinical trial subject in physical examination, vital sign tests, diagnostic examination, and 12-lead ECG by the medical doctor, etc. Exclusion Criteria: 1. A person who has a clinically significant history of the disease, such as liver, kidney, gastrointestinal disease, respiratory tract disease, muscular-skeletal disease, endocrine disease, nervous system disease, blood ∙ tumor disease, cardiovascular disease, etc. 2. A person who has a history of gastrointestinal diseases or surgery that may affect the absorption of IP, etc. **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 19 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Seongnam-si **Country:** Korea, Republic of **Facility:** Seoul National University Bundang Hospital **State:** Gyeonggi-do **Zip:** 13620 #### Overall Officials **Official 1:** **Affiliation:** Seoul National University Bundang Hospital **Name:** Jae-Yong Chung **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000011500 - Term: Protein Synthesis Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M351859 - Name: Delpazolid - Relevance: HIGH - As Found: Penpulimab - ID: M22872 - Name: Oxazolidinones - Relevance: HIGH - As Found: Penpulimab - ID: M4222 - Name: Anti-Bacterial 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: C000627008 - Term: Delpazolid - ID: D000023303 - Term: Oxazolidinones ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00003279 **Acronym:** SILVA **Brief Title:** Vaccination Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer **Official Title:** The SILVA Study: Survival in an International Phase III Prospective Randomized LD Small Cell Lung Cancer Vaccination Study With Adjuvant BEC2 and BCG #### Organization Study ID Info **ID:** EORTC-08971 #### Organization **Class:** NETWORK **Full Name:** European Organisation for Research and Treatment of Cancer - EORTC #### Secondary ID Infos **ID:** EORTC-08971 **ID:** UCLA-9902001 ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2012-03-06 **Type:** ESTIMATED **Last Update Submit Date:** 2012-03-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2000-01 **Type:** ACTUAL #### Start Date **Date:** 1998-03 **Status Verified Date:** 2012-03 #### Study First Post Date **Date:** 2004-08-25 **Type:** ESTIMATED **Study First Submit Date:** 1999-11-01 **Study First Submit QC Date:** 2004-08-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NETWORK **Name:** European Organisation for Research and Treatment of Cancer - EORTC #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** RATIONALE: Vaccines may help the body build an immune response to kill tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of vaccination with monoclonal antibody BEC2 and BCG with that of no further therapy in treating patients who have limited-stage small cell lung cancer. **Detailed Description:** OBJECTIVES: I. Determine the impact of adjuvant monoclonal antibody BEC2 and BCG on survival of patients with limited stage small cell lung cancer. II. Determine the safety of this regimen in these patients. III. Determine progression-free survival and quality of life of these patients treated with this regimen. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, Karnofsky performance status (60-70% vs 80-100%), and response to first-line combined modality treatment (complete vs partial). Within 3-7 weeks after completion of prior induction chemoradiotherapy, responding patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive best supportive care and are observed until disease progression is documented. Arm II: Patients receive adjuvant monoclonal antibody BEC2 and BCG intradermally on day 1 of weeks 0, 2, 4, 6, and 10. Treatment consists of 5 vaccinations over a period of 10 to 12 weeks in the absence of unacceptable toxicity or disease progression. Quality of life is assessed at baseline, at weeks 6, 12, and 24, and then every 6 months thereafter. Patients are followed every 3 months. PROJECTED ACCRUAL: Approximately 500 patients will be accrued for this study within 4 years. ### Conditions Module **Conditions:** - Lung Cancer **Keywords:** - limited stage small cell lung cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 500 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** BCG vaccine **Type:** BIOLOGICAL #### Intervention 2 **Name:** monoclonal antibody BEC2 **Type:** BIOLOGICAL ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: Histologically or cytologically proven limited stage small cell lung cancer (SCLC) Must have completed adequate first-line combined modality treatment comprising at least 4-6 courses of a 2-drug chemotherapy regimen and chest radiotherapy No evidence of disease progression or relapse Disease response (complete or partial) after treatment PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: WBC greater that 3,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: AST less than 1.5 times upper limit of normal Hepatitis B negative Renal: Not specified Cardiovascular: Adequate cardiac function Other: HIV negative Not pregnant or nursing Fertile patients must use effective contraception No prior malignancy within 5 years except adequately treated nonmelanomatous skin cancer or carcinoma in situ of the cervix No history of tuberculosis No grade 3 local skin toxicity reaction (ulceration) to 5 IU or greater of PPD test No active infections requiring systemic antibiotics, antiviral, or antifungal treatments No serious unstable chronic illnesses No psychological, familial, sociological, or geographical condition that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: No prior therapy with proteins of murine origin At least one month since prior immunotherapy No other concurrent immunotherapy Chemotherapy: See Disease Characteristics No concurrent chemotherapy Endocrine therapy: No concurrent chronic use of systemic corticosteroids Radiotherapy: See Disease Characteristics No concurrent radiotherapy including prophylactic cranial irradiation No prior spleen radiotherapy Surgery: No prior surgery for SCLC No prior splenectomy Other: No prior second-line therapy for SCLC At least one month since prior investigational agents No concurrent chronic use of systemic antihistamines or nonsteroidal anti-inflammatory drugs No concurrent immunosuppressive therapy **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 Comprehensive Cancer Center **State:** Alabama **Zip:** 35294 **Location 2:** **City:** Scottsdale **Country:** United States **Facility:** Mayo Clinic Scottsdale **State:** Arizona **Zip:** 85259 **Location 3:** **City:** La Jolla **Country:** United States **Facility:** Scripps Clinic and Research Foundation - La Jolla **State:** California **Zip:** 92037 **Location 4:** **City:** Los Angeles **Country:** United States **Facility:** Jonsson Comprehensive Cancer Center, UCLA **State:** California **Zip:** 90095-1781 **Location 5:** **City:** Denver **Country:** United States **Facility:** Colorado Permanente Medical Group, P.C. **State:** Colorado **Zip:** 80205 **Location 6:** **City:** Bridgeport **Country:** United States **Facility:** Bridgeport Hospital **State:** Connecticut **Zip:** 06610 **Location 7:** **City:** Greenwich **Country:** United States **Facility:** Greenwich Hospital Association **State:** Connecticut **Zip:** 06830 **Location 8:** **City:** Hartford **Country:** United States **Facility:** St. Francis Hospital and Medical Center **State:** Connecticut **Zip:** 06105 **Location 9:** **City:** Norwich **Country:** United States **Facility:** Norwich Cancer Center **State:** Connecticut **Zip:** 06360 **Location 10:** **City:** Stamford **Country:** United States **Facility:** Bennett Cancer Center **State:** Connecticut **Zip:** 06902 **Location 11:** **City:** Washington **Country:** United States **Facility:** Veterans Affairs Medical Center - Washington, DC **State:** District of Columbia **Zip:** 20422 **Location 12:** **City:** Hollywood **Country:** United States **Facility:** Memorial Regional Cancer Center **State:** Florida **Zip:** 33021 **Location 13:** **City:** Miami **Country:** United States **Facility:** Mercy Hospital **State:** Florida **Zip:** 33133 **Location 14:** **City:** Miami **Country:** United States **Facility:** Sylvester Cancer Center, University of Miami **State:** Florida **Zip:** 33136 **Location 15:** **City:** North Miami Beach **Country:** United States **Facility:** Columbia - HCA Cancer Research Network **State:** Florida **Zip:** 33180 **Location 16:** **City:** Atlanta **Country:** United States **Facility:** Emory University School of Medicine **State:** Georgia **Zip:** 30322 **Location 17:** **City:** Decatur **Country:** United States **Facility:** Georgia Cancer Specialists **State:** Georgia **Zip:** 30033 **Location 18:** **City:** West Roxbury **Country:** United States **Facility:** Veterans Affairs Medical Center - West Roxbury **State:** Massachusetts **Zip:** 02132 **Location 19:** **City:** Saint Louis Park **Country:** United States **Facility:** CCOP - Metro-Minnesota **State:** Minnesota **Zip:** 55416 **Location 20:** **City:** Great Falls **Country:** United States **Facility:** Benefis Healthcare **State:** Montana **Zip:** 59403 **Location 21:** **City:** Great Falls **Country:** United States **Facility:** Great Falls Clinic **State:** Montana **Zip:** 59405 **Location 22:** **City:** Las Vegas **Country:** United States **Facility:** Southwest Cancer Clinic **State:** Nevada **Zip:** 89119 **Location 23:** **City:** Reno **Country:** United States **Facility:** University of Nevada - Reno **State:** Nevada **Zip:** 89520 **Location 24:** **City:** East Orange **Country:** United States **Facility:** Veterans Affairs Medical Center - East Orange **State:** New Jersey **Zip:** 07018-1095 **Location 25:** **City:** Buffalo **Country:** United States **Facility:** Veterans Affairs Medical Center - Buffalo **State:** New York **Zip:** 14215 **Location 26:** **City:** New York **Country:** United States **Facility:** Memorial Sloan-Kettering Cancer Center **State:** New York **Zip:** 10021 **Location 27:** **City:** Durham **Country:** United States **Facility:** Duke Comprehensive Cancer Center **State:** North Carolina **Zip:** 27710 **Location 28:** **City:** Akron **Country:** United States **Facility:** Akron City Hospital **State:** Ohio **Zip:** 44309 **Location 29:** **City:** Cincinnati **Country:** United States **Facility:** Christ Hospital **State:** Ohio **Zip:** 45219 **Location 30:** **City:** Tulsa **Country:** United States **Facility:** Oklahoma Oncology Inc. **State:** Oklahoma **Zip:** 74104 **Location 31:** **City:** Providence **Country:** United States **Facility:** Rhode Island Hospital **State:** Rhode Island **Zip:** 02903 **Location 32:** **City:** Lubbock **Country:** United States **Facility:** Joe Arrington Cancer Research and Treatment Center **State:** Texas **Zip:** 79410-1894 **Location 33:** **City:** Charleston **Country:** United States **Facility:** Charleston Area Medical Center **State:** West Virginia **Zip:** 25304 **Location 34:** **City:** Madison **Country:** United States **Facility:** University of Wisconsin Comprehensive Cancer Center **State:** Wisconsin **Zip:** 53792 **Location 35:** **City:** Camperdown **Country:** Australia **Facility:** Royal Prince Alfred Hospital, Sydney **State:** New South Wales **Zip:** 2050 **Location 36:** **City:** Concord **Country:** Australia **Facility:** Repatriation General Hospital **State:** New South Wales **Zip:** 2139 **Location 37:** **City:** Newcastle **Country:** Australia **Facility:** Newcastle Mater Misericordiae Hospital **State:** New South Wales **Zip:** NSW 2310 **Location 38:** **City:** Penrith **Country:** Australia **Facility:** Nepean Hospital **State:** New South Wales **Zip:** 2750 **Location 39:** **City:** St. Leonards **Country:** Australia **Facility:** Royal North Shore Hospital **State:** New South Wales **Zip:** 2065 **Location 40:** **City:** Westmead **Country:** Australia **Facility:** NSW Breast Cancer Institute **State:** New South Wales **Zip:** 2145 **Location 41:** **City:** Adelaide **Country:** Australia **Facility:** Royal Adelaide Hospital **State:** South Australia **Zip:** 5000 **Location 42:** **City:** East Bentweigh **Country:** Australia **Facility:** Monash Medical Center **State:** Victoria **Zip:** 3165 **Location 43:** **City:** East Melbourne **Country:** Australia **Facility:** Peter MacCallum Cancer Institute **State:** Victoria **Zip:** 8006 **Location 44:** **City:** Parkville **Country:** Australia **Facility:** Royal Melbourne Hospital **State:** Victoria **Zip:** 3050 **Location 45:** **City:** Perth **Country:** Australia **Facility:** Royal Perth Hospital **State:** Western Australia **Zip:** 6000 **Location 46:** **City:** Vienna (Wein) **Country:** Austria **Facility:** Pulmologisches Zentrum Der Stadt Wien **Zip:** A-1145 **Location 47:** **City:** Leuven **Country:** Belgium **Facility:** U.Z. Gasthuisberg **Zip:** B-3000 **Location 48:** **City:** Berlin **Country:** Germany **Facility:** Universitaetsklinikum Benjamin Franklin **Zip:** D-12200 **Location 49:** **City:** Gauting, Munich (Munchen) **Country:** Germany **Facility:** Asklepios Fachkliniken Munchen- Gauting **Zip:** DOH-8-2131 **Location 50:** **City:** Grosshansdorf **Country:** Germany **Facility:** Hospital Grosshansdorf **Zip:** D-22927 **Location 51:** **City:** Heidelberg **Country:** Germany **Facility:** Thoraxklinik Rohrbach **Zip:** D-69126 **Location 52:** **City:** Herne **Country:** Germany **Facility:** Marienhospital/Ruhr University Bochum **Zip:** DOH-4-4625 **Location 53:** **City:** 's-Hertogenbosch **Country:** Netherlands **Facility:** Groot Ziekengasthuis 's-Hertogenbosch **Zip:** 5211 NL **Location 54:** **City:** Amsterdam **Country:** Netherlands **Facility:** Academisch Ziekenhuis der Vrije Universiteit **Zip:** 1007 MB **Location 55:** **City:** Harderwijk **Country:** Netherlands **Facility:** Ziekenhuis St Jansdal **Zip:** 3840 AC **Location 56:** **City:** Nieuwegein **Country:** Netherlands **Facility:** Sint Antonius Ziekenhuis **Zip:** 3435 CM **Location 57:** **City:** Tilburg **Country:** Netherlands **Facility:** Twee Steden Ziekenhuis Vestiging Tilburg **Zip:** 5042 AD **Location 58:** **City:** Auckland **Country:** New Zealand **Facility:** Green Lane Hospital **Zip:** 3 **Location 59:** **City:** Wellington **Country:** New Zealand **Facility:** Wellington Cancer Centre **Zip:** 6039 **Location 60:** **City:** Barakaldo, Bilbao **Country:** Spain **Facility:** Hospital de Cruces **Zip:** E-48903 **Location 61:** **City:** Barcelona **Country:** Spain **Facility:** Hospital de la Santa Cruz I Sant Pau **Zip:** 08025 **Location 62:** **City:** Barcelona **Country:** Spain **Facility:** Ciudad Sanitaria Vall D'Hebron **Zip:** 08035 **Location 63:** **City:** Barcelona **Country:** Spain **Facility:** Hospital Clinic y Provincial de Barcelona **Zip:** 08036 **Location 64:** **City:** Elche **Country:** Spain **Facility:** Hospital Universitario de Elche **Zip:** E-03203 **Location 65:** **City:** Madrid **Country:** Spain **Facility:** Hospital de la Princesa **Zip:** 28006 **Location 66:** **City:** Madrid **Country:** Spain **Facility:** Hospital Universitario 12 de Octubre **Zip:** 28041 **Location 67:** **City:** San Sebastian **Country:** Spain **Facility:** Hospital Nostra Senora Aranzazu **Location 68:** **City:** Valencia **Country:** Spain **Facility:** Hospital Universitario LA FE **Zip:** 46009 **Location 69:** **City:** Valencia **Country:** Spain **Facility:** Hospital Clinico Universitario de Valencia **Zip:** 46010 **Location 70:** **City:** Valencia **Country:** Spain **Facility:** Hospital General Universitario Valencia **Zip:** 46014 **Location 71:** **City:** Valencia **Country:** Spain **Facility:** Hospital Arnau Vilanova **Zip:** 46015 **Location 72:** **City:** Zaragoza **Country:** Spain **Facility:** Hospital Miguel Servet **Zip:** 50009 **Location 73:** **City:** Basel **Country:** Switzerland **Facility:** University Hospital **Zip:** CH-4031 **Location 74:** **City:** Bern **Country:** Switzerland **Facility:** Inselspital, Bern **Zip:** CH-3010 **Location 75:** **City:** Chur **Country:** Switzerland **Facility:** Ratisches Kantons und Regionalspital **Zip:** CH-7000 **Location 76:** **City:** Saint Gallen **Country:** Switzerland **Facility:** Kantonsspital - Saint Gallen **Zip:** CH-9007 **Location 77:** **City:** Sutton **Country:** United Kingdom **Facility:** Royal Marsden Hospital **State:** England **Zip:** SM2 5PT #### Overall Officials **Official 1:** **Affiliation:** Free University Medical Center **Name:** Giuseppe Giaccone, MD, PhD **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Bottomley A, Debruyne C, Felip E, Millward M, Thiberville L, D'Addario G, Rome L, Zatloukal P, Coens C, Giaccone G. Symptom and quality of life results of an international randomised phase III study of adjuvant vaccination with Bec2/BCG in responding patients with limited disease small-cell lung cancer. Eur J Cancer. 2008 Oct;44(15):2178-84. doi: 10.1016/j.ejca.2008.06.036. **PMID:** 18676140 ## Derived Section ### Condition Browse Module - Ancestors - 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 - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: HIGH - As Found: Lung Cancer - ID: M28323 - Name: Small Cell Lung Carcinoma - Relevance: HIGH - As Found: Small Cell Lung Cancer - ID: M5534 - Name: Carcinoma - 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: T5271 - Name: Small Cell Lung Cancer - Relevance: HIGH - As Found: Small Cell Lung Cancer ### Condition Browse Module - Meshes - ID: D000008175 - Term: Lung Neoplasms - ID: D000055752 - Term: Small Cell Lung Carcinoma ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000276 - Term: Adjuvants, Immunologic ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown - ID: M4225 - Name: Antibodies - Relevance: HIGH - As Found: Program - ID: M4230 - Name: Antibodies, Monoclonal - Relevance: HIGH - As Found: Chemotherapy - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M4793 - Name: BCG Vaccine - Relevance: HIGH - As Found: Right and left - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M3628 - Name: Adjuvants, Immunologic - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000000906 - Term: Antibodies - ID: D000000911 - Term: Antibodies, Monoclonal - ID: D000001500 - Term: BCG Vaccine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00111579 **Brief Title:** Study to Evaluate the Immune Responses of Trivalent Cold-Adapted Influenza Vaccine (CAIV-T) Compared With (TIV) **Official Title:** A Prospective, Randomized, Open-Label Study to Evaluate the Immune Responses of Trivalent Cold-Adapted Influenza Vaccine (CAIV-T) Compared With Trivalent Inactivated Vaccine (TIV) in Children 6 to <36 Months of Age #### Organization Study ID Info **ID:** MI-CP123 #### Organization **Class:** INDUSTRY **Full Name:** MedImmune LLC ### Status Module #### Completion Date **Date:** 2006-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2008-07-24 **Type:** ESTIMATED **Last Update Submit Date:** 2008-07-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2006-01 **Type:** ACTUAL #### Start Date **Date:** 2005-05 **Status Verified Date:** 2008-07 #### Study First Post Date **Date:** 2005-05-24 **Type:** ESTIMATED **Study First Submit Date:** 2005-05-23 **Study First Submit QC Date:** 2005-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** MedImmune LLC #### Responsible Party **Old Name Title:** Chris Ambrose, Dir. Medical Affairs **Old Organization:** MedImmune LLC ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to describe the level of serum antibody conferred by CAIV-T and TIV against homotypic and heterotypic influenza virus strains. ### Conditions Module **Conditions:** - Influenza ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 52 **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** CAIV-T **Intervention Names:** - Biological: CAIV-T **Label:** 1 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** TIV **Intervention Names:** - Other: TIV **Label:** 2 **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** A total vol. of 0.2 mL will be administered intranasally (approx. 0.1 mL into each nostril)for ea. of two doses. **Name:** CAIV-T **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - 2 **Description:** A total vol. of 0.25 will be administered intramuscularly for each of two doeses. **Name:** TIV **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** The following immunogenicity endpoints: The strain-specific HAI seroconversion rates (≥ 4-fold increase) among baseline seronegative participants (HAI titer ≤ 1:4), by dose number **Time Frame:** Day 28 post final vaccination **Measure:** The proportion of participants achieving ≥ 4-fold increase in strain-specific HAI titer from baseline in all participants regardless of baseline serostatus, by dose number **Time Frame:** Day 28 post final vaccination #### Secondary Outcomes **Measure:** Safety endpoints include: AEs SAEs and significant new medical conditions for all participants **Time Frame:** Day 28 post vaccination ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or Female * Ages 6 to but less than 36 months (reached their 6th month but have not yet reached their 3rd birthday) at the time of randomization * Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization (if applicable) obtained from the participant's parent/legal representative * Ability of the parent/legal representative to understand and comply with the requirements of the study * Parent/legal representative available by telephone * Ability to complete follow-up period of 180 days after final study vaccination, as required by the protocol Exclusion Criteria: * History of hypersensitivity to any component of CAIV-T or TIV, including egg or egg products, monosodium glutamate, porcine gelatin or thimerosal * History of hypersensitivity to gentamicin * Any known immunosuppressive condition or immune deficiency disease (including HIV infection), or ongoing receipt of any immunosuppressive therapy * Household contact who is immunocompromised (participants should also avoid close contact with immunocompromised individuals for at least 21 days after each study vaccination) * History of Guillain-Barre syndrome * Medically diagnosed wheezing, bronchodilator use, or steroid use (systemic or inhaled), by parent/legal representative report or chart review, within the 42 days prior to randomization (i.e., children with recent persistent asthma are excluded); or history of severe persistent asthma, according to the criteria described in the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma - Update on Selected Topics 2002 * Acute febrile (not greater than 100.0 degrees F oral or equivalent) and/or clinically significant respiratory illness (e.g., cough or sore throat) within 72 hours prior to either study vaccination * Use of aspirin or aspirin-containing products within 30 days prior to randomization, or expected use through 180 days after final study vaccination * Receipt of any prior influenza vaccine * Use of anti-influenza medications (including amantadine, rimantadine, oseltamivir, and zanamivir) within 14 days prior to randomization, or expected use through 180 days after final study vaccination * Administration of any live virus vaccine within 30 days prior to randomization, or expected receipt through 30 days after final study vaccination * Administration of any inactivated (i.e., non-live) vaccine within 14 days prior to randomization, or expected receipt within 14 days before, or 14 days after, either study vaccination * Receipt of any investigational agent within 30 days prior to randomization, or expected receipt through 180 days after final study vaccination (use of licensed agents for indications not listed in the package insert is permitted) * Receipt of any blood product within 90 days prior to randomization, or expected receipt through 180 days after final study vaccination * Family member or household contact who is an employee of the research center or otherwise involved with the conduct of the study * Any condition that, in the opinion of the investigator, would interfere with evaluation of the vaccine or interpretation of the study results **Healthy Volunteers:** True **Maximum Age:** 36 Months **Minimum Age:** 6 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Layton **Country:** United States **Facility:** Wee Care Pediatrics **State:** Utah **Zip:** 84041 **Location 2:** **City:** Ogden **Country:** United States **Facility:** Bear Care Pediatrics **State:** Utah **Zip:** 84405 **Location 3:** **City:** Pleasant Grove **Country:** United States **Facility:** Alpine Pediatrics **State:** Utah **Zip:** 84062 **Location 4:** **City:** Provo **Country:** United States **Facility:** Utah Valley Pediatrics **State:** Utah **Zip:** 84604 **Location 5:** **City:** South Jordan **Country:** United States **Facility:** Families First Pediatrics **State:** Utah **Zip:** 84095 #### Overall Officials **Official 1:** **Affiliation:** MedImmune LLC **Name:** Robert Walker, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000009976 - Term: Orthomyxoviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus 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: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M10295 - Name: Influenza, Human - Relevance: HIGH - As Found: Influenza - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M12902 - Name: Orthomyxoviridae 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: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007251 - Term: Influenza, Human ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03972579 **Brief Title:** Behavioral Profile Matching: A Precision Medicine Approach to Concussion Rehabilitation **Official Title:** Behavioral Profile Matching: A Precision Medicine Approach to Concussion Rehabilitation #### Organization Study ID Info **ID:** H18-02344 #### Organization **Class:** OTHER **Full Name:** University of British Columbia ### Status Module #### Completion Date **Date:** 2021-07-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-11-16 **Type:** ACTUAL **Last Update Submit Date:** 2021-11-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-02-15 **Type:** ACTUAL #### Start Date **Date:** 2019-05-15 **Type:** ACTUAL **Status Verified Date:** 2021-11 #### Study First Post Date **Date:** 2019-06-03 **Type:** ACTUAL **Study First Submit Date:** 2019-05-22 **Study First Submit QC Date:** 2019-05-31 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** Canadian Institutes of Health Research (CIHR) #### Lead Sponsor **Class:** OTHER **Name:** University of British Columbia #### Responsible Party **Investigator Affiliation:** University of British Columbia **Investigator Full Name:** Noah Silverberg **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:** At least 1 in 5 people who sustain a concussion will have persistent symptoms and difficulties with daily activities. The researchers have identified two unhelpful coping styles following a concussion - avoidance and endurance. Individuals who engage in avoidance behavior may benefit from a different type of treatment than those who engage in endurance behavior. The researchers will evaluate whether assigning individuals to a specific psychologically-informed treatment tailored to their coping style is practical, acceptable, and beneficial for their recovery. **Detailed Description:** Psychosocial factors are known to affect recovery from concussion, but are not sufficiently taken into account by current treatment approaches. Distinct behavioral profiles after concussion have emerged in our research: (1) avoidance, where individuals perceive activity as overly dangerous and take care to avoid overexertion, and (2) endurance, where individuals persist with high levels of activity despite worse symptoms until they "crash," requiring recuperative rest. The researchers hypothesize that patients with these behavioral profiles likely benefit from different treatment approaches. The next step in our research program is to evaluate the feasibility and potential impact of tailoring therapies based on an Avoidance-Endurance Model adapted from the chronic pain literature. The proposed project aims to evaluate whether matching patients with concussion to tailored therapies based on their behavioral profile (avoidance vs endurance) is feasible. A secondary aim is to test our hypothesis that participants receiving the intervention matched to their behavioral profile will have less post-treatment disability than mismatched participants. In a pilot double-blind (patient, assessor) RCT with 1:1 allocation stratified by behavioral profile (avoidance vs. endurance), 64 adults with persistent symptoms after concussion will complete an initial evaluation, an activity diary over the following week, and then be randomized to receive an interdisciplinary treatment package tailored to avoidance or endurance profiles. In brief, the program designed for avoidance will involve graded exposure to cognitively demanding activity (e.g., mental math exercises), physical exertion (e.g., treadmill jogging), and sensory stimulation (e.g., scenes with visual motion). The focus of the endurance program will be pacing, i.e., shifting from symptom-contingent to time-contingent behavior. A blinded assessor will administer outcome measures 12 weeks after enrollment. Feasibility criteria include acceptability of randomization and treatment tolerability, fidelity, and adherence. Proposed changes to "profile matching" study due to COVID-19 pandemic (March 30, 2020) Due to the COVID-19 pandemic, there will be no new enrollments as of March 30, 2020. The study will continue to be advertised at concussion clinic group education sessions, which are now being held virtually, but inform prospective participants that enrollment will be postponed by at least one month. Interested patients will be added to a waitlist for screening when the study resumes enrollment (once COVID-19 social distancing restrictions are lifted and non-essential business/services are resumed). For participants who have expressed interest in the study and/or have already been screened, but have not completed their baseline assessment: Defer baseline assessment. Inform the participant that the study will resume enrolling when COVID-19 restrictions have been lifted. They will keep their place on a study waitlist. Patients who have been screened will need to be re-screened when enrollment resumes. For participants who have completed their baseline assessment or are already active in treatment: Continue treatment per protocol. However, participants who have completed no more than 25% of treatment (4 of 16 sessions) should be offered the option of a temporary stoppage for at least one month (i.e., the target of completing all 16 sessions within 10 weeks can be dropped). If the therapists believe that treatment progress is being significantly impeded by COVID-19 restrictions, they may suggest a stoppage. The final decision about stoppage should be made by the participant. If they prefer a stoppage, the therapists should contact the participant in one month to decide whether to resume treatment or delay by another month. Any stoppages should be communicated to the study coordinator. For participants who completed treatment, or at least 75% of their treatment (12 of 16 sessions), by March 13, 2020 but did not complete their outcome assessment until after that date: Complete the outcome assessment per protocol, but add one question immediately following the WHODAS. Introduce the question as follows: "These questions were about how much difficulty you had with various activities due to your health conditions over the past month. In other words, I asked you focus on difficulties caused by your concussion and/or other health conditions. However, the investigators recognize that it might be hard to ignore circumstances other than your health conditions when answering these questions." Ask: "To what extent were your answers to these questions affected by the COVID-19 pandemic?" If they ask what "affected by the COVID-19 pandemic" means, the research assistant may provide examples: "Such as all of sudden being laid off or asked to work overtime, or not being able to go out because of social distancing policies." Provide responses: 0=minimally or not at all, 1=somewhat, 2=quite a bit, 3=very much or entirely. Confirm their response by asking "So, were it not for the COVID-19 pandemic, would you have answered these questions ___________ differently?" Please also record (free text) notes if participants provide explanations or reasons. Note that this additional question is being asked only for the primary study outcome (WHODAS). This question will be removed from the protocol one month after COVID-19 social distancing restrictions are lifted and non-essential business/services are resumed. Changes to the statistical analysis plan: Participants whose treatment progress and/or outcome assessment was likely substantially impacted by COVID-19 will be excluded from the primary analysis. Participants who treatment progress and/or outcome assessment was possibly mildly impacted, but not likely substantially impacted, by COVID-19 will be included in the primary analysis. This will be operationalized according to the Table 1 below. Participants who are eligible (completed no more than 4 therapy sessions by March 30, 2020) and choose to temporarily stop treatment during the COVID-19 disruption period will not be counted in the numerator or denominator for calculating the retention rate as a feasibility outcome. Coding the COVID_status variable: 0 Operational definition: 0a. Participants who completed their outcome assessment by March 13, 2020. 0b. Participants who completed at least 75% of their treatment (12 of 16 sessions) by March 13, 2020 and the outcome assessment between March 14 and on April 30\*, and answered 0 or 1 to the WHODAS COVID question. 0c. Participants who completed no more than 25% of their treatment (0-4 therapy sessions) by March 30, 2020 and agreed to temporarily stop treatment (before their 5th therapy session) until after April 30, 2020\*. 0d. Participants who enrolled after April 30, 2020\*. 0e. Participants who meet criteria 1b or 1c (below) but both of their therapists agreed with the statement "therapy goals and progress were not affected by COVID-19" and the participant answered 0 or 1 to the WHODAS COVID question. -Represents participants whose therapy progress and outcome assessment were minimally or not affected by COVID-19 disruptions. It captures participants who did most or all of their therapy outside of the COVID-19 disruption period, as well as the few who continued therapy unimpeded by COVID-19 disruptions. These participants will be included the primary analysis. Coding the COVID_status variable: 1 Operational definition: 1a. Participants who completed at least 75% of their treatment (12 of 16 sessions) by March 13, 2020 and their outcome assessment between March 14-April 30, 2020\*, and answered 2 or 3 to the WHODAS COVID-19 question. 1b. Participants who completed more than 25% but less than 75% of their treatment (i.e., 5-11 sessions) by March 30, 2020, and do not meet criterion 0e. 1c. Participants who completed no more than 25% of their treatment (0-4) by March 30, 2020 and chose to continue treatment during the period in which COVID-19 social distancing restrictions, and do not meet criterion 0e. -Represents participants whose therapy progress and/or outcome assessment were likely affected by COVID-19 disruptions. These participants will be excluded from primary analysis. \*Note: March 14, 2020 is the start of the COVID-19 disruption period in British Columbia, when the first social distancing policies were introduced. April 30, 2020 is a placeholder date for when COVID-19 social distancing restrictions are lifted and non-essential business/services are resumed. The actual date will be updated. ### Conditions Module **Conditions:** - Mild Traumatic Brain Injury ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 64 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Weekly 60-min sessions with an occupational therapist and psychologist over 8 weeks. **Intervention Names:** - Behavioral: Graded exposure therapy **Label:** Graded exposure therapy **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Weekly 60-min sessions with an occupational therapist and psychologist over 8 weeks. **Intervention Names:** - Behavioral: Pacing + mindfulness **Label:** Pacing + mindfulness **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Graded exposure therapy **Description:** Gradually increased contact with avoided sensory stimuli (e.g., light, noise, movement) and activities (e.g., mental exertion, physical exercise, stressful activities) in order to increase tolerance. **Name:** Graded exposure therapy **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Pacing + mindfulness **Description:** Shifting from symptom-contingent to time-contingent activity stopping rules, minimizing activity level peaks (excessive endurance behavior) and valleys (prolonged periods of recuperative rest) to improve overall functioning. **Name:** Pacing + mindfulness **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Measure:** World Health Organization Disability Assessment Schedule (WHODAS) 2.0 12-item **Time Frame:** Initial assessment, past 30 days. #### Secondary Outcomes **Measure:** Rivermead Postconcussion Symptom Questionnaire **Time Frame:** initial assessment, past 24 hours. ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * Aged 18-70 years old. * Sustained a mild traumatic brain injury between 1 and 12 months ago. * Fluent in English. * Access to a computer, tablet, or smartphone with internet capability. * 3+ persistent moderate-severe symptoms on the Rivermead Postconcussion Symptom Questionnaire. * High avoidance (Fear Avoidance Behavior after Traumatic Brain Injury; FAB-TBI) and/or endurance behavior (Behavioral Response to Illness Questionnaire - All-Nothing subscale). Exclusion criteria: * Patients with a cardiac contraindication to aerobic exercise will be excluded **Healthy Volunteers:** True **Maximum Age:** 69 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Vancouver **Country:** Canada **Facility:** GF Strong Rehab Centre **State:** British Columbia **Zip:** V5Z 2G9 #### Overall Officials **Official 1:** **Affiliation:** University of British Columbia **Name:** Noah Silverberg, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Terpstra AR, Louie DR, Iverson GL, Yeates KO, Picon E, Leddy JJ, Silverberg ND. Psychological Contributions to Symptom Provocation Testing After Concussion. J Head Trauma Rehabil. 2023 Mar-Apr 01;38(2):E146-E155. doi: 10.1097/HTR.0000000000000796. Epub 2022 Jun 9. **PMID:** 35687896 **Citation:** Silverberg ND, Cairncross M, Brasher PMA, Vranceanu AM, Snell DL, Yeates KO, Panenka WJ, Iverson GL, Debert CT, Bayley MT, Hunt C, Baker A, Burke MJ; Canadian Traumatic Brain Injury Research Consortium (CTRC). Feasibility of Concussion Rehabilitation Approaches Tailored to Psychological Coping Styles: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2022 Aug;103(8):1565-1573.e2. doi: 10.1016/j.apmr.2021.12.005. Epub 2021 Dec 28. **PMID:** 34971596 **Citation:** Terpstra AR, Cairncross M, Yeates KO, Vranceanu AM, Greenberg J, Hunt C, Silverberg ND. Psychological mediators of avoidance and endurance behavior after concussion. Rehabil Psychol. 2021 Nov;66(4):470-478. doi: 10.1037/rep0000390. Epub 2021 Aug 19. **PMID:** 34410757 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000006259 - Term: Craniocerebral Trauma - ID: D000020196 - Term: Trauma, Nervous System - ID: D000014947 - Term: Wounds and Injuries - ID: D000016489 - Term: Head Injuries, Closed - ID: D000014949 - Term: Wounds, Nonpenetrating ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5207 - Name: Brain Injuries - Relevance: HIGH - As Found: Brain Injury - ID: M628 - Name: Brain Injuries, Traumatic - Relevance: HIGH - As Found: Traumatic Brain Injury - ID: M5201 - Name: Brain Concussion - Relevance: HIGH - As Found: Mild Traumatic Brain Injury - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M9349 - Name: Craniocerebral Trauma - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown - ID: M18892 - Name: Head Injuries, Closed - Relevance: LOW - As Found: Unknown - ID: M17687 - Name: Wounds, Nonpenetrating - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001930 - Term: Brain Injuries - ID: D000070642 - Term: Brain Injuries, Traumatic - ID: D000001924 - Term: Brain Concussion ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M16759 - Name: Tin Fluorides - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03180879 **Brief Title:** Ibuprofen Bioavailability Study **Official Title:** An Open Label, Randomised, Single Dose, Three-way Crossover Study to Compare the Bioavailability of 400 mg Ibuprofen From 2 x 200 mg Ibuprofen Acid Orodispersable Tablets, 2x 200 mg Ibuprofen Acid Tablets and 2 x 342 mg Ibuprofen Lysine Tablets in Fasted Healthy Volunteers #### Organization Study ID Info **ID:** RB7-UK-1604 #### Organization **Class:** INDUSTRY **Full Name:** Reckitt Benckiser Healthcare (UK) Limited ### Status Module #### Completion Date **Date:** 2017-06-13 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-10-05 **Type:** ACTUAL **Last Update Submit Date:** 2017-10-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-06-13 **Type:** ACTUAL #### Start Date **Date:** 2017-04-10 **Type:** ACTUAL **Status Verified Date:** 2017-04 #### Study First Post Date **Date:** 2017-06-08 **Type:** ACTUAL **Study First Submit Date:** 2017-05-17 **Study First Submit QC Date:** 2017-06-06 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Simbec Research #### Lead Sponsor **Class:** INDUSTRY **Name:** Reckitt Benckiser Healthcare (UK) Limited #### 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 project is the in-house development of a 200 mg ibuprofen acid orodispersable tablet (ODT; meltlet). It is designed to appeal to consumers who want a dosage form that may be taken without water and can be used 'on the go'. Vanquish has an improved organoleptic profile compared to the currently marketed meltet by the Sponsor. ODTs are also considered as a suitable dosage form for children who may be reluctant to swallow tablets. This product has the potential for application in both adults and children due to the convenience of the format and the ease of administration for both groups. This will be the first pharmacokinetic (PK) assessment of the ibuprofen acid ODT formulation. ### Conditions Module **Conditions:** - Healthy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 36 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Treatment Order: Test, Reference, Comparator **Intervention Names:** - Drug: Test - RB ibuprofen acid orodispersible tablets - Drug: Reference - RB Nurofen ibuprofen acid tablets - Drug: Comparator - Dolormin ibuprofen lysine tablets **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Treatment Order: Test, Comparator, Reference **Intervention Names:** - Drug: Test - RB ibuprofen acid orodispersible tablets - Drug: Reference - RB Nurofen ibuprofen acid tablets - Drug: Comparator - Dolormin ibuprofen lysine tablets **Label:** 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Treatment Order: Reference, Test, Comparator **Intervention Names:** - Drug: Test - RB ibuprofen acid orodispersible tablets - Drug: Reference - RB Nurofen ibuprofen acid tablets - Drug: Comparator - Dolormin ibuprofen lysine tablets **Label:** 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Treatment Order: Reference, Comparator, Test **Intervention Names:** - Drug: Test - RB ibuprofen acid orodispersible tablets - Drug: Reference - RB Nurofen ibuprofen acid tablets - Drug: Comparator - Dolormin ibuprofen lysine tablets **Label:** 4 **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Treatment Order: Comparator, Test, Reference **Intervention Names:** - Drug: Test - RB ibuprofen acid orodispersible tablets - Drug: Reference - RB Nurofen ibuprofen acid tablets - Drug: Comparator - Dolormin ibuprofen lysine tablets **Label:** 5 **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** Treatment Order: Comparator, Reference, Test **Intervention Names:** - Drug: Test - RB ibuprofen acid orodispersible tablets - Drug: Reference - RB Nurofen ibuprofen acid tablets - Drug: Comparator - Dolormin ibuprofen lysine tablets **Label:** 6 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 - 2 - 3 - 4 - 5 - 6 **Description:** RB ibuprofen acid orodispersible tablets, 2 x 200 mg, single dose, oral. **Name:** Test - RB ibuprofen acid orodispersible tablets **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 1 - 2 - 3 - 4 - 5 - 6 **Description:** RB Nurofen ibuprofen acid tablets, 2 x 200 mg, single dose, oral. **Name:** Reference - RB Nurofen ibuprofen acid tablets **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - 1 - 2 - 3 - 4 - 5 - 6 **Description:** Dolormin ibuprofen lysine tablets 2 x 342 mg (each 342 mg tablet contains 200 mg ibuprofen), single dose, oral. **Name:** Comparator - Dolormin ibuprofen lysine tablets **Type:** DRUG ### Outcomes Module #### Other Outcomes **Measure:** Overall proportion of subjects with adverse events (AEs), i.e. the occurrence of one or more AEs per subject **Time Frame:** Through study completion - Screening to study follow-up (approx 6 weeks) **Description:** Measured in degrees Celcius **Measure:** Change from baseline in oral temperature. **Time Frame:** Through study completion - Screening to study follow-up (approx 6 weeks) **Description:** Measured in beats per minute **Measure:** Change from baseline in resting heart rate. **Time Frame:** Through study completion - Screening to study follow-up (approx 6 weeks) **Description:** Measured in mmHg **Measure:** Change from baseline in resting blood pressure.. **Time Frame:** Through study completion - Screening to study follow-up (approx 6 weeks) **Measure:** Change from baseline in standard haematology testing. **Time Frame:** Through study completion - Screening to study follow-up (approx 6 weeks) **Measure:** Change from baseline in standard biochemistry testing. **Time Frame:** Through study completion - Screening to study follow-up (approx 6 weeks) **Measure:** Change from baseline in standard urinary testing. **Time Frame:** Through study completion - Screening to study follow-up (approx 6 weeks) #### Primary Outcomes **Description:** The Test and Reference will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Reference ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%: **Measure:** AUC0-t - the area under plasma concentration curve from administration to last quantifiable concentration at time t. **Time Frame:** PK Analysis 0-12hrs **Description:** The Test and Reference will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Reference ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%: **Measure:** Cmax - the maximum observed plasma concentration. **Time Frame:** PK Analysis 0-12hrs #### Secondary Outcomes **Description:** The Test and Comparator will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%: **Measure:** AUC0-t - the area under plasma concentration curve from administration to last quantifiable concentration at time t. **Time Frame:** PK Analysis 0-12hrs **Description:** The Test and Comparator will be considered similar if for ibuprofen, for each corresponding PK parameter, the 90% confidence interval for the Test to Comparator ratio (rounded to two decimal places) of LS geometric means is fully contained within the interval 80.00 to 125.00%: **Measure:** Cmax - the maximum observed plasma concentration. **Time Frame:** PK Analysis 0-12hrs **Description:** Secondary endpoint for Test, Reference and Comparator products **Measure:** Kel - Elimination rate constant **Time Frame:** PK Analysis 0-12hrs **Description:** Secondary endpoint for Test, Reference and Comparator products **Measure:** AUC0-inf - Area under the plasma concentration-time curve from administration to infinity **Time Frame:** PK Analysis 0-12hrs **Description:** Secondary endpoint for Test, Reference and Comparator products **Measure:** AUCR - Ratio AUC0-t/AUC0-inf **Time Frame:** PK Analysis 0-12hrs **Description:** Secondary endpoint for Test, Reference and Comparator products **Measure:** Tmax - Time until Cmax is first achieved **Time Frame:** PK Analysis 0-12hrs **Description:** Secondary endpoint for Test, Reference and Comparator products **Measure:** T1/2 - Plasma concentration (elimination) half-life **Time Frame:** PK Analysis 0-12hrs **Description:** Secondary endpoint for Test, Reference and Comparator products **Measure:** Cn - The plasma concentration at each planned nominal time point. **Time Frame:** PK Analysis 0-12hrs ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Male or female subjects who have given written informed consent. 2. Age: ≥ 18 years ≤ 50 years. 3. Body Mass Index (BMI) of ≥ 18.0 and ≤ 30 kg/m2. 4. Healthy as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening. 5. Female subject of child bearing potential with a negative pregnancy test at the screening visit and willing to use an effective method of contraception unless of non-childbearing potential or where abstaining from sexual intercourse in line with the preferred and usual lifestyle of the subject from first dose until 3 months after the final dose of study medication. 6. Female subject of non-child bearing potential with negative pregnancy test at the screening visit. 7. Male subject willing to use an effective method of contraception unless anatomically sterile or where abstaining from sexual intercourse in line with the preferred and usual lifestyle of the subject from first dose until 3 months after the final dose of study medication. Exclusion Criteria: 1. Pregnant or lactating females. 2. A history and/or presence of significant disease of any body system, including significant psychiatric disorders, parasuicide. 3. Any condition that may currently interfere with the absorption, distribution, metabolism or excretion of drugs. 4. A history of allergy or intolerance related to treatment with ibuprofen, aspirin or other non-steriodal anti-inflammatory drugs (NSAIDs), or the excipients of the formulations 5. A history of or active peptic or duodenal ulcers or gastrointestinal bleed or upper gastro-intestinal bleed, or other significant gastro-intestinal disorders. 6. A history of frequent dyspepsia, e.g. heartburn or indigestion. 7. A history of significant and frequent migraine. 8. Current smokers or ex-smokers who have smoked or used nicotine replacement products during the 6 months prior to the first dose of study medication. 9. A history of substance abuse (including alcohol). 10. Consumption of foods or beverages containing caffeine (e.g. coffee, tea, cola and chocolate) above 300 mg caffeine per day, prior to 48 hours of each treatment period. (One cup of coffee equals approximately 50 mg caffeine). 11. Those with positive test for drugs of abuse and alcohol. 12. Ingestion of a prescribed drug at any time in the 14 days before the first dose of study medication (excluding hormonal contraceptives and hormone replacement therapy), or consumption of enzyme inhibitors or inducers 30 days prior to the first dose of study medication (such as barbiturates, carbamazepine, erythromycin, phenytoin, etc.). 13. Ingestion of an over-the-counter preparation within 7 days before the first dose of study medication, including herbal medications, vitamins, fish oil supplements, ibuprofen and other NSAIDs. 14. Those who have consumed grapefruit or grapefruit juice, pumelo or Seville oranges in the 7 days before the first dose of study medication. 15. Donation of blood \> 400 mL e.g. to the blood transfusion service in the 12 weeks prior to the first dose of study medication. 16. Known human immune deficiency virus (HIV) positive status, or a positive viral serology test. 17. Topical use of ibuprofen within 7 days before the first dose of study medication. 18. Strenuous physical exercise from 48 hours prior to first dose of study medication. 19. Those previously randomised into this study. 20. Those who are an employee at the study site. 21. Those who are a partner or first degree relative of the Investigator. 22. Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of study medication. 23. Those unable in the opinion of the Investigator to comply fully with the study requirements. **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Merthyr Tydfil **Country:** United Kingdom **Facility:** Simbec Research #### Overall Officials **Official 1:** **Affiliation:** Simbec Research **Name:** Annelize Koch, MBBS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Sugar D, Francombe D, da Silva T, Hanid S, Hutchings S. Comparative Bioavailability Study of a New Orodispersible Formulation of Ibuprofen Versus Two Existing Oral Tablet Formulations in Healthy Male and Female Volunteers. Clin Ther. 2019 Aug;41(8):1486-1498. doi: 10.1016/j.clinthera.2019.04.040. Epub 2019 Jun 12. **PMID:** 31202508 ## Derived Section ### 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: 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 - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M10102 - Name: Ibuprofen - Relevance: HIGH - As Found: Last - 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: M19209 - Name: Cyclooxygenase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: T11 - Name: Lysine - Relevance: HIGH - As Found: Craving ### Intervention Browse Module - Meshes - ID: D000007052 - Term: Ibuprofen ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00406679 **Brief Title:** Analgesic Efficacy, Safety and Tolerability of Two Paracetamol-containing Solutions in Post-Surgical Dental Pain **Official Title:** Single-Dose Comparison of the Analgesic Efficacy, Safety and Tolerability of Two Paracetamol 1%-Containing Solutions and Placebo in a Post-Surgical Dental Pain Model #### Organization Study ID Info **ID:** R-01270-A015 #### Organization **Class:** INDUSTRY **Full Name:** Baxter Healthcare Corporation #### Secondary ID Infos **ID:** EudraCT2005-005575-14 ### Status Module #### Completion Date **Date:** 2007-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2011-08-11 **Type:** ESTIMATED **Last Update Submit Date:** 2011-08-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-10 **Type:** ACTUAL #### Start Date **Date:** 2006-11 **Status Verified Date:** 2011-08 #### Study First Post Date **Date:** 2006-12-04 **Type:** ESTIMATED **Study First Submit Date:** 2006-11-29 **Study First Submit QC Date:** 2006-11-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Baxter Healthcare Corporation #### Responsible Party **Old Name Title:** Keyvan Tadjalli Mehr, MD **Old Organization:** Baxter Healthcare Corporation ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of the study is to evaluate the therapeutic efficacy and safety of two different paracetamol-containing solutions in postoperative dental pain. They will be compared to placebo (a dummy treatment which contains no active ingredient). ### Conditions Module **Conditions:** - Pain, Postoperative **Keywords:** - pain, postoperative - surgery, oral - surgery, dental ### 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:** 135 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Paracetamol (acetaminophen) solution experimental **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: placebo **Label:** 2 **Type:** PLACEBO_COMPARATOR #### Arm Group 3 **Intervention Names:** - Drug: paracetamol (acetaminophen) solution commercial **Label:** 3 **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** 1 gm IV **Name:** Paracetamol (acetaminophen) solution experimental **Other Names:** - paracetamol - acetaminophen **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 3 **Description:** 1 gm IV **Name:** paracetamol (acetaminophen) solution commercial **Other Names:** - paracetamol - acetaminophen **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - 2 **Description:** equivalent volume IV 0.9% sodium chloride (equivalent volume) **Name:** placebo **Other Names:** - sodium chloride - saline **Type:** DRUG ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ASA I or II and scheduled for elective surgical extraction of 1 or more impacted mandibular 3rd molars, at least 1 of which must be a fully or partially impacted mandibular 3rd molar requiring mandibular bone removal. * Moderate or severe pain within 4 hours after the completion of surgery. Exclusion Criteria: * Another acute or chronic painful physical condition * Use of any other analgesics (within 24 hours), sedatives, or narcotic drugs as well as microsomal enzyme inducers * Inability to use and understand Visual Analog Scale and Verbal Rating Score **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Manchester **Country:** United Kingdom **Facility:** University Dental Hospital of Manchester **State:** England **Location 2:** **City:** Cardiff **Country:** United Kingdom **Facility:** University Dental Hospital NHS Trust Cardiff **State:** Wales #### Overall Officials **Official 1:** **Affiliation:** Baxter Healthcare Corporation **Name:** Keyvan Tadjalli-Mehr, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011183 - Term: Postoperative Complications - ID: D000010335 - Term: Pathologic Processes - 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: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M13069 - Name: Pain, Postoperative - Relevance: HIGH - As Found: Pain, Postoperative - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M16853 - Name: Toothache - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010149 - Term: Pain, Postoperative ### Intervention Browse Module - Ancestors - 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: D000058633 - Term: Antipyretics ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics - Abbrev: Antipy - Name: Antipyretics ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: HIGH - As Found: Procedure - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M2340 - Name: Acetaminophen - Relevance: HIGH - As Found: Compared - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M29176 - Name: Antipyretics - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000000082 - Term: Acetaminophen - ID: D000019999 - Term: Pharmaceutical Solutions ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03048279 **Brief Title:** Registry for Multiple Endocrine Neoplasia Syndromes: MEN1/MEN2 **Official Title:** Registry for Multiple Endocrine Neoplasia Syndromes: MEN1/MEN2 #### Organization Study ID Info **ID:** RCR01-485 #### Organization **Class:** OTHER **Full Name:** M.D. Anderson Cancer Center #### Secondary ID Infos **Domain:** NCI CTRP Clinical Trials Reporting Registry **ID:** NCI-2021-12213 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2026-09-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-10 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-08 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2026-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2001-09-05 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2017-02-09 **Type:** ESTIMATED **Study First Submit Date:** 2017-02-07 **Study First Submit QC Date:** 2017-02-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** M.D. Anderson Cancer 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:** Objectives: To contribute new and prospective data to our existing database library for patients with MEN1 and MEN2 at The University of Texas M.D. Anderson Cancer Center. **Detailed Description:** Previously followed MEN1 and MEN2 patients at M.D. Anderson Cancer Center will be mailed an introductory letter and a "consent to be contacted" form to determine whether they are interested in participating in the study. New MEN1 and MEN2 patients seen in clinic at M.D. Anderson Cancer Center will be asked if they wish to learn more about this study. Interested patients will also be asked to distribute the introductory letter and consent to be contacted form to their blood relatives. Printed materials regarding this study will only be mailed to non-MDACC individuals with the expressed written or verbal permission from a consenting MDACC patient. All interested individuals will return the signed "consent to be contacted" form to the PI. Consented individuals will be interviewed by phone and/or mail to obtain updated family and medical history specific to their diagnosis of either MEN1 or MEN2. To verify accuracy of medical data collected, all non-MDACC participants will be asked if they consent to have their off-site medical records released to us for review. There will be no treatment or collection of blood or tissue in this study. Although this study presents minimal risk to participants, participant consent will be obtained due to the need to obtain permission to make contact with patients and their families. Approximately 1500 patients and their relatives will be included in this study. This will be done on an inpatient and outpatient basis. ### Conditions Module **Conditions:** - Multiple Endocrine Neoplasia Syndromes **Keywords:** - Multiple Endocrine Neoplasia Syndromes - MEN1 - MEN2 - Relatives - Database - Questionnaires - Surveys ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1500 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Consented individuals will be interviewed by phone and/or mail to obtain medical history specific to their diagnosis of either MEN1 or MEN2. **Intervention Names:** - Behavioral: Questionnaires **Label:** Multiple Endocrine Neoplasia Syndromes: MEN1/MEN2 #### Arm Group 2 **Description:** Participants will be asked to complete a health and family history questionnaire. This questionnaire process may be completed by phone or mail. **Intervention Names:** - Behavioral: Questionnaires **Label:** Close Relatives of Registered MDACC MEN Patients ### Interventions #### Intervention 1 **Arm Group Labels:** - Close Relatives of Registered MDACC MEN Patients - Multiple Endocrine Neoplasia Syndromes: MEN1/MEN2 **Description:** Multiple Endocrine Neoplasia Syndromes: MEN1/MEN2 Group: Participants interviewed by phone and/or mail to obtain medical history specific to their diagnosis of either MEN1 or MEN2. Close Relatives of Registered MDACC MEN Patients Group: Participants asked to complete a health and family history questionnaire. This questionnaire process may be completed by phone or mail. **Name:** Questionnaires **Other Names:** - Surveys **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Measure:** Contribution of New and Prospective Data to Existing Database Library for Patients with MEN1 and MEN2 by Completion of Health Questionnaires **Time Frame:** 25 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Registered MDACC patients diagnosed with MEN1 or MEN2. 2. Close relatives of registered MDACC MEN patients. Exclusion Criteria: 1. Individuals who are either non-MDACC registered patients or do not have a close relative who is an MEN patient registered at MDACC. **Healthy Volunteers:** True **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** MEN1 and MEN2 patients at M.D. Anderson Cancer Center and their relatives ### Contacts Locations Module #### Locations **Location 1:** **City:** Houston **Country:** United States **Facility:** University of Texas MD Anderson Cancer Center **State:** Texas **Zip:** 77030 #### Overall Officials **Official 1:** **Affiliation:** M.D. Anderson Cancer Center **Name:** Nancy D. Perrier, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### See Also Links **Label:** University of Texas MD Anderson Cancer Center **URL:** http://www.mdanderson.org ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000009371 - Term: Neoplasms by Site - ID: D000004700 - Term: Endocrine System Diseases - ID: D000009378 - Term: Neoplasms, Multiple Primary - ID: D000009386 - Term: Neoplastic Syndromes, Hereditary - ID: D000030342 - Term: Genetic Diseases, Inborn ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: HIGH - As Found: Endocrine Neoplasia - ID: M12322 - Name: Multiple Endocrine Neoplasia - Relevance: HIGH - As Found: Multiple Endocrine Neoplasia - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M12323 - Name: Neoplasms, Multiple Primary - Relevance: LOW - As Found: Unknown - ID: M12331 - Name: Neoplastic Syndromes, Hereditary - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: T3935 - Name: Multiple Endocrine Neoplasia Type 2 - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009369 - Term: Neoplasms - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000009377 - Term: Multiple Endocrine Neoplasia - ID: D000013577 - Term: Syndrome ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04840979 **Brief Title:** Discovery and Validation of Genetic Variants Affecting Microglial Activation in Alzheimer's Disease **Official Title:** Discovery and Validation of Genetic Variants Affecting Microglial Activation in Alzheimer's Disease With 11C-ER176 #### Organization Study ID Info **ID:** AAAT2774 #### Organization **Class:** OTHER **Full Name:** Columbia University #### Secondary ID Infos **ID:** RF1AG070438 **Link:** https://reporter.nih.gov/quickSearch/RF1AG070438 **Type:** NIH ### Status Module #### Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-26 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Start Date **Date:** 2021-05-11 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2021-04-12 **Type:** ACTUAL **Study First Submit Date:** 2021-04-08 **Study First Submit QC Date:** 2021-04-08 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute on Aging (NIA) #### Lead Sponsor **Class:** OTHER **Name:** Columbia University #### Responsible Party **Investigator Affiliation:** Columbia University **Investigator Full Name:** Philip De Jager **Investigator Title:** Weil-Granat Professor of Neurology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The primary objectives are to validate that a previously identified gene variant influences the proportion of activated microglia (PAM) and the amount of TSPO binding on PET imaging, to identify novel loci that influence PAM and TSPO PET, and to understand the functional consequences of gene variants that drive microglial activation in Alzheimer's disease. **Detailed Description:** While activated microglia have been observed in the vicinity of neuritic amyloid plaques in Alzheimer's disease (AD), there have been no large-scale assessments of microglial activation in aging and neurodegenerative disease. The investigators seek to understand the genetic underpinning of microglial responses-particularly the proportion of microglia in a morphologically-defined state of activation-that increase susceptibility to AD, so the investigators can develop more targeted forms of immune-based therapies to prevent cognitive decline and progression to dementia. The objective is to refine the genetic architecture of microglial activation to validate a previously identified gene variant -- and to identify novel loci -- that influence the proportion of activated microglia. The investigators also seek to understand the functional consequences of variants driving microglial activation in AD. The central hypothesis is that identifiable gene variants influence microglial activation and susceptibility to AD. The investigators will test this hypothesis by conducting genome-wide analysis and identifying associations between gene variants and microglial activation. Microglial activation will be measured in human autopsy tissue (ex vivo), living human brain using PET imaging (in vivo), and in monocyte-derived microglia-like cells (in situ and in vitro). This genetic study is designed to validate a finding that was discovered in participants with self-reported European-Caucasian ancestry. Therefore, the study seeks to enroll participants who self-report as white, not Hispanic or Latino. However, if this study is successful, the investigators plan to use the methods in this protocol in a future study to identify new genetic variants associated with changes on TSPO PET in a more diverse participant population. The investigators intend to use the results from this study to eventually benefit individuals of all racial and ethnic groups. ### Conditions Module **Conditions:** - Alzheimer Disease **Keywords:** - PET scan - Inflammation - Genetic testing - Cognitive Impairment ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 250 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects diagnosed with Alzheimer's disease (AD) or mild cognitive impairment (MCI) will have one PET scan with 11C-ER176, with arterial sampling. If the subject lacks known AD-biomarkers, they may undergo a 18F-florbetaben PET scan prior to the 11C-ER176 PET scan. Genome-wide genetic analysis will be performed. Participants will undergo an annual clinical evaluation and blood sample collection for 5 years to establish the trajectory of AD-related serum biomarkers and syndromic diagnoses. **Intervention Names:** - Drug: 11C-ER176 - Drug: 18F-florbetaben **Label:** Cognitive Impairment **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Healthy volunteers who are cognitively normal will have one PET scan with 11C-ER176, with arterial sampling. If the subject lacks known AD-biomarkers, they may undergo an 18F-florbetaben PET scan prior to the 11C-ER176 PET scan. Genome-wide genetic analysis will be performed. Participants will undergo an annual clinical evaluation and blood sample collection for 5 years to establish the trajectory of AD-related serum biomarkers and syndromic diagnoses. **Intervention Names:** - Drug: 11C-ER176 - Drug: 18F-florbetaben **Label:** No Cognitive Impairment **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Cognitive Impairment - No Cognitive Impairment **Description:** 11C-ER176 is a novel TSPO radioligand that was developed because of its relative insensitivity to the rs6971 polymorphism. Increased TSPO signal on PET is associated with activation of microglia in the brain. The radioligand will be administered in tracer doses at activity of up to 20 mCi (740 MBq), IV, total of one injection. A single dose of radioligand will be injected over 1 minute. **Name:** 11C-ER176 **Other Names:** - [11C]ER176 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Cognitive Impairment - No Cognitive Impairment **Description:** Florbetaben has been approved by the FDA to help diagnose Alzheimer's disease. Florbetaben measures amyloid in the brain. **Name:** 18F-florbetaben **Other Names:** - [18F] Florbetaben **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The measure will be in vivo validation of GWAS and assessment of clinical relevance by performing TSPO PET imaging using 11C-ER176 to measure microglial activation. PET images will be analyzed using 1) the two-tissue kinetic model to calculate total distribution volume, corrected for free fraction of radioligand in plasma (VT/fP). Analysis will be a meta-analysis of the association of rs2997325 with 11C-ER176 binding (total distribution volume, VT). **Measure:** Correlation between the chromosome 1 variant (rs2997325) and TSPO binding **Time Frame:** Up to 1 year **Description:** 11C-ER176 data will be used to perform a discovery GWAS for additional variants that influence TSPO binding and to define the genetic architecture of the PAM trait. Using PLINK and all imputed high quality genotypes (imputation r2 \>0.8), adjusted for sex, age, and technical variables, the investigators will perform a GWAS for TSPO binding. **Measure:** Number of variants discovered in genome-wide association study (GWAS) that influence TSPO binding **Time Frame:** Up to 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: 1. Age 50 and older at time of study entry. 2. Meet criteria for either a) amnestic mild cognitive impairment (single or mixed domain) or Alzheimer's disease, or b) have no cognitive impairment, based on history, exam, and neuropsychological testing. 3. Patients must have Clinical Dementia Rating Scale score of 0.5 or 1 at enrollment. Controls must have Clinical Dementia Rating scale score of 0 at enrollment. 4. Subjects must have AD biomarker previously obtained for research or clinical purposes or undergo a 18F-florbetaben PET scan during the screening process. Patients must have positive amyloid PET scan or CSF results consistent with AD. Controls must have a negative amyloid PET scan or CSF results not consistent with AD. 5. Self-identify as white, non-Hispanic or Latino 6. Subjects must be ableto provide informed consent 7. Written and oral fluency in English 8. Able to participate in all scheduled evaluations and to complete all required tests and procedures. 9. In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study. Exclusion Criteria: 1. Past or present history of certain brain disorders other than MCI or AD. 2. Certain significant medical conditions, which make study procedures of the current study unsafe. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries. 3. Contraindication to MRI scanning 4. Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.). 5. Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits. 6. Participation in the last year in a clinical trial for a disease modifying drug for AD. 7. Inability to have a catheter in subject's vein for the injection of radioligand. 8. Inability to have blood drawn from subject's veins. 9. Taking anticoagulant (e.g., warfarin) or immunosuppressive/immunomodulatory medication. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not exclusionary. Use of steroids in the 30 days preceding the PET scan. 10. Having a diagnosis of a chronic inflammatory disease (for example, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus) or a chronic infectious disease such as H.I.V. **Healthy Volunteers:** True **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Galen Ziaggi **Phone:** 212-305-9079 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Elena Golub **Phone:** 212-305-9079 **Role:** CONTACT #### Locations **Location 1:** **City:** New York **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Galen Ziaggi - **Phone:** 212-305-9079 - **Role:** CONTACT ***Contact 2:*** - **Name:** Philip De Jager, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Columbia University Irving Medical Center **State:** New York **Status:** RECRUITING **Zip:** 10032 #### Overall Officials **Official 1:** **Affiliation:** Columbia University **Name:** Philip De Jager, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Investigator qualifications and previous work will be reviewed by PI. Subsequent email correspondence will relay technical criteria needed for access. **Description:** Individual participant data will be available upon reasonable request from a qualified investigator. **IPD Sharing:** YES **Time Frame:** Up to two weeks after review and approval of request. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003704 - Term: Dementia - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000024801 - Term: Tauopathies - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000019965 - Term: Neurocognitive Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M29705 - Name: Cognitive Dysfunction - Relevance: LOW - As Found: Unknown - ID: M3885 - Name: Alzheimer Disease - Relevance: HIGH - As Found: Alzheimer's Disease - ID: M6904 - Name: Dementia - 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: M23002 - Name: Tauopathies - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M21836 - Name: Neurocognitive 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: T2192 - Name: Familial Alzheimer Disease - Relevance: HIGH - As Found: Alzheimer's Disease ### Condition Browse Module - Meshes - ID: D000000544 - Term: Alzheimer Disease ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01345279 **Brief Title:** Indirect Comparison Topotecan Cervical Carcinoma **Official Title:** Indirect Comparison of the Efficacy Between Topotecan and Other Treatments for Recurrent Carcinoma of the Cervix #### Organization Study ID Info **ID:** 114016 #### Organization **Class:** INDUSTRY **Full Name:** GlaxoSmithKline ### Status Module #### Completion Date **Date:** 2009-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-05-30 **Type:** ACTUAL **Last Update Submit Date:** 2017-05-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-07 **Type:** ACTUAL #### Start Date **Date:** 2009-06 **Status Verified Date:** 2017-05 #### Study First Post Date **Date:** 2011-05-02 **Type:** ESTIMATED **Study First Submit Date:** 2010-07-16 **Study First Submit QC Date:** 2011-04-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Indirect comparisons were performed using data from GOG-0179 versus GOG-0169 to permit comparison of topotecan in combination with cisplatin versus cisplatin plus paclitaxel via the common comparator of cisplatin monotherapy. Both GOG-0179 and GOG-0169 were conducted in patients with stage IVB, recurrent or persistent carcinoma of the cervix, but there were some differences between the respective study populations. Patients with prior chemotherapy were eligible for GOG-0179 but ineligible for GOG-0169 (except when chemotherapy was used for radiation sensitisation). Fewer patients had received chemotherapy as a radiosensitiser in GOG-0169 (27%) than in GOG-0179 (\~60%) and these patients were unevenly distributed between treatment arms in GOG-0169. In addition, the proportion of patients receiving cisplatin as a radiosensitiser in GOG-0169 is unknown. For these reasons, there are limitations associated with the indirect meta-analysis. ### Conditions Module **Conditions:** - Cervical Intraepithelial Neoplasia ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 1 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: cisplatin **Label:** cisplatin #### Arm Group 2 **Intervention Names:** - Drug: cisplatin - Drug: topotecan **Label:** cisplatin + topotecan #### Arm Group 3 **Intervention Names:** - Drug: cisplatin - Drug: paclitaxel **Label:** cisplatin + paclitaxel ### Interventions #### Intervention 1 **Arm Group Labels:** - cisplatin - cisplatin + paclitaxel - cisplatin + topotecan **Description:** 50 mg/m2 IV cisplatin on day 1 and then every 3 weeks for 6 courses **Name:** cisplatin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - cisplatin + topotecan **Description:** topotecan 0.75 mg/m2 on days 1, 2, and 3. The regimen was repeated every 3 weeks for 6 courses **Name:** topotecan **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - cisplatin + paclitaxel **Description:** 135 mg/m2 paclitaxel on day 1 and then every 3 weeks for 6 courses **Name:** paclitaxel **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Overall survival **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * randomised clinical trials, or systematic reviews and meta-analyses * treatment with topotecan or platinum-based single and combination regimens in female patients of any race with cancer of the cervix recurrent after radiotherapy or stage IVB disease Exclusion Criteria: * None **Minimum Age:** 21 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** The search was designed to identify all clinical data published since the Cancer Care Ontario systematic review in 2006. The Cancer Care Ontario systematic review searched MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006), the Cochrane Library (Cochrane Database of Systematic Reviews (2006 Issue 1), and Cochrane Controlled Trials Register (2006 Issue 1)), the Canadian Medical Association Infobase, and the National Guidelines Clearinghouse. The conference proceedings of the American Society of Clinical Oncology (1995-2005) and the European Society of Medical Oncology (2002-2005) were also searched. The search was completed on 18 December 2008 ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** GlaxoSmithKline **Name:** GSK Clinical Trials **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000011230 - Term: Precancerous Conditions - 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: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M5826 - Name: Uterine Cervical Dysplasia - Relevance: HIGH - As Found: Cervical Intraepithelial Neoplasia - ID: M14111 - Name: Precancerous Conditions - 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 - ID: T1074 - Name: Cervical Intraepithelial Neoplasia - Relevance: HIGH - As Found: Cervical Intraepithelial Neoplasia ### Condition Browse Module - Meshes - ID: D000002578 - Term: Uterine Cervical Dysplasia ### Intervention Browse Module - Ancestors - ID: D000000972 - Term: Antineoplastic Agents, Phytogenic - ID: D000000970 - Term: Antineoplastic Agents - ID: D000050257 - Term: Tubulin Modulators - ID: D000050256 - Term: Antimitotic Agents - ID: D000050258 - Term: Mitosis Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000059004 - Term: Topoisomerase I Inhibitors - ID: D000059003 - Term: Topoisomerase Inhibitors - 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: M19537 - Name: Paclitaxel - Relevance: HIGH - As Found: Surgery - ID: M231 - Name: Albumin-Bound Paclitaxel - Relevance: LOW - As Found: Unknown - ID: M21674 - Name: Topotecan - Relevance: HIGH - As Found: PD-1 - ID: M6182 - Name: Cisplatin - Relevance: LOW - As Found: Unknown - ID: M26197 - Name: Tubulin Modulators - Relevance: LOW - As Found: Unknown - ID: M26196 - Name: Antimitotic Agents - Relevance: LOW - As Found: Unknown - ID: M29349 - Name: Topoisomerase I Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000017239 - Term: Paclitaxel - ID: D000019772 - Term: Topotecan ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02175979 **Acronym:** SANICSII **Brief Title:** SANICS II Trial: Stimulation of the Autonomic Nervous System in Colorectal Surgery by Perioperative Nutrition **Official Title:** SANICS II Trial: A Multicenter Prospective Double-blind Randomized Controlled Trial Investigating the Effect of Stimulation of the Autonomic Nervous System in Colorectal Surgery by Perioperative Nutrition #### Organization Study ID Info **ID:** NL45640.060.13 #### Organization **Class:** OTHER **Full Name:** Catharina Ziekenhuis Eindhoven ### Status Module #### Completion Date **Date:** 2017-12-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-09-19 **Type:** ACTUAL **Last Update Submit Date:** 2019-08-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-03-20 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-09-19 **Type:** ACTUAL **Results First Submit Date:** 2019-05-03 **Results First Submit QC Date:** 2019-08-14 #### Start Date **Date:** 2014-08 **Status Verified Date:** 2019-08 #### Study First Post Date **Date:** 2014-06-26 **Type:** ESTIMATED **Study First Submit Date:** 2014-06-25 **Study First Submit QC Date:** 2014-06-25 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Danone Research **Class:** OTHER **Name:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) **Class:** OTHER **Name:** ZonMw: The Netherlands Organisation for Health Research and Development **Class:** OTHER **Name:** Fonds NutsOhra #### Lead Sponsor **Class:** OTHER **Name:** Misha D.P. Luyer #### Responsible Party **Investigator Affiliation:** Catharina Ziekenhuis Eindhoven **Investigator Full Name:** Misha D.P. Luyer **Investigator Title:** dr. M.D.P. Luyer **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The main objective is to investigate the effects of perioperative nutrition on postoperative ileus and anastomotic leakage in patients undergoing colorectal surgery. Perioperative enteral nutrition is compared to the standard of care (fasting perioperatively). **Detailed Description:** Postoperative ileus (POI) and anastomotic leakage (AL) are important clinical determinants of short-term morbidity and mortality following colorectal surgery. Importantly, AL is also a risk factor for local recurrence of colorectal cancer and has a significant impact on disease-free and overall survival. It is therefore believed that improving postoperative outcome following colorectal surgery will also improve long-term oncological outcomes regarding overall survival and tumour recurrence. POI is a common complication after colorectal surgery that causes discomfort for the patient but also leads to a prolonged hospital length of stay and increasing health care costs. For POI it is believed that formation of an inflammatory infiltrate in the muscular layers of the intestine following bowel manipulation during surgery leads to a decreased gastrointestinal motility. In recent years the investigators have demonstrated in experimental models that administration of enteral nutrition modulates the inflammatory response via the autonomic nervous system by release of cholecystokinin (CCK). Composition of the enteral nutrition and timing of administration are both essential for the magnitude of effect. For the most optimal effect, nutrition is given with a higher fraction of lipids and protein and is administered just before, during and directly after the inciting event. In this way, the inflammatory response is optimally dampened via release of CCK. In an experimental study has been shown that such a lipid-enriched enteral nutrition reduces systemic inflammation and postoperative ileus in a CCK-dependent manner when given just before and directly after bowel manipulation. Next, the investigators performed a study in healthy volunteers in which the effect of continuous low volume enteral nutrition was investigated on inflammatory parameters in a human endotoxemia model. In this study was shown that lipid enriched nutrition reduced the inflammatory response upon endotoxemia in man. Also in a clinical setting the investigators have shown that enteral nutrition reduces inflammation and postoperative ileus. In a randomized controlled trial the investigators have shown that enteral nutrition early after colorectal surgery reduced POI. Furthermore, in a model of sham-feeding using chewing gum was shown that inflammation and postoperative ileus were reduced following colorectal surgery. Interestingly, both clinical studies with sham feeding and early enteral nutrition revealed a yet unaccountable effect on anastomotic leakage. Evidence on the relation between POI and anastomotic leakage is scarce but has great impact. It seems that an early intervention with enteral nutrition shortly before, during and early after colorectal surgery may reduce inflammation and reduce important determinants in postoperative morbidity as POI and anastomotic leakage. All patients will receive a self-migrating nasojejunal tube one day before surgery. The position of the nasojejunal tube is verified by means of an X-ray at the night before surgery. Preoperatively, patients receive standard of care with a fast for solid (oral) food of 6 hours and a (oral) fluid fast for 2 hours before administration. Three hours before surgery the pump is started to administer nutrition in standardized amounts. Enriched enteral nutrition (produced by Danone research) is administered via a programmed Flocare enteral feeding pump. The pump is connected to the opaque branched system that is connected both to the nasojejunal tube and to a sealed container. Patients are either allocated to the experimental group, in which the blinded branched system leads the enteral nutrition via the nasojejunal tube to the patient. Via this route, the patients in the experimental group will receive the enteral nutrition just before, during and directly after surgery. In patients allocated to the control group, the blinded branched system leads the enteral nutrition to the container. Consequently, when the feeding pump starts just before surgery, patients in the control group do not receive the nutrition. In both groups, the pump with enteral nutrition is stopped 6 hours after surgery and normal intake is resumed. Based on previous results a power calculation is performed. For POI a sample size of at least 91 patients per group is needed based on a power of 0.8 and an alpha of 0.05. For AL a reduction of AL of at least 75% was observed in the previous clinical studies. Using a power of 0.8 and a drop-out percentage of 5% a total of 140 patients are needed per group. Since perioperative nutrition is a new concept, a safety analysis is performed after inclusion of 40 patients in which feasibility and safety of preoperative nutrition are assessed. The effect size is determined based on previous studies and is substantial. Considering the size of the effect, an interim-analysis will be performed after inclusion of 140 patients. All analyses will be done according to the intention-to-treat approach in which all randomized patients are included, regardless of adherence to the study protocol. Occurrences of the primary and secondary endpoints are compared between the treatment groups. Results are presented as risk ratios with corresponding 95% confidence intervals. A two-tailed P \< 0.05 is considered statistically significant. To compare the groups, the data will be tested for normal distribution and an unpaired T-test will be performed when appropriate, otherwise the Mann-Whitney U or Chi-square tests. SPSS (Statistical Package for the Social Sciences version 20) will be used to analyze the data. The investigators respect the Dutch Scientific Code of conduct with regard to collection and storage of our data. The investigators hereby mind the criteria of retrievability, accessibility and interchangeability of the data. The investigators will obtain written informed consent from all patients, in which is stated that their records will be used and saved for research purposes for a minimum of 15 years. Anonymity and confidentiality of data will be guaranteed compliant with CBP (Commission Protection of Personal Data) guidelines. Thus, all variables will be registered anonymously, but via a secured code, personally identifiable information can be retrieved. The investigators verified completeness of patient Data Management Strategy via the Data Archiving and Networked Services checklist. Rough data will be stored in a digital archive, with appended description, to interpret the data. ### Conditions Module **Conditions:** - Postoperative Ileus - Anastomotic Leak **Keywords:** - postoperative ileus - anastomotic leak - colorectal surgery - inflammation ### 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:** 280 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** standard of care **Intervention Names:** - Dietary Supplement: standard **Label:** standard **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** enriched enteral tube feeding 1.5ml/ minute perioperative **Intervention Names:** - Dietary Supplement: enriched enteral nutrition **Label:** enriched enteral nutrition **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - enriched enteral nutrition **Description:** enriched enteral tube feeding perioperative **Name:** enriched enteral nutrition **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - standard **Description:** standard of care **Name:** standard **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** number of patients with absence of flatus or stool passage and inability to tolerate a regular oral diet between surgery and postoperative day 4 **Measure:** Number of Patients Developing Postoperative Ileus **Time Frame:** up to 3 weeks after surgery #### Secondary Outcomes **Description:** number of patients developing anastomotic leakage **Measure:** Anastomotic Leakage **Time Frame:** up to 6 weeks after surgery **Description:** number of patients developing aspiration pneumonia **Measure:** Aspiration Pneumonia **Time Frame:** up to 3 week after surgery **Description:** Percent change in Gastric Antral Area, assessed by Ultrasound of the Gastric Antrum Following a Standardized Meal **Measure:** Gastric Motility **Time Frame:** 3 days after surgery **Description:** Length of functional recovery in days, Functional recovery was defined as postoperative patients not receiving intravenous fluid who have adequate pain control, restoration ofindependent mobility, sufficient caloric intake, and no signs of active infection **Measure:** Functional Recovery **Time Frame:** up to 6 weeks after surgery **Description:** the inflammatory response measured systemically (in blood): C-reactive protein (CRP) **Measure:** C-reactive Protein (CRP) **Time Frame:** up to 48 hours after surgery **Description:** number of patients needing additional surgical, radiological or endoscopic interventions: All surgical complications are classified using the Clavien-Dindo classification. patients with a Clavien Dindo grade IIIa, IIIb, IVa, IVb, V complication had a surgical, radiological or endoscopic intervention. **Measure:** Number of Patients Needing Additional Surgical, Radiological or Endoscopic Interventions **Time Frame:** up to 6 weeks after surgery **Description:** number of patients needing ICU admission after surgery **Measure:** Number of Patients Needing ICU Admission **Time Frame:** up to 6 weeks after surgery **Description:** Global Quality of life on a scale ranging from 0 to 100, with higher scores indicating higher level of functioning. The EORTC QLQ C-30 questionnaires are used **Measure:** Health-related Quality of Life **Time Frame:** 6 months after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * patients that undergo elective surgical resection of the colon or rectum with primary anastomosis. * written informed consent * age \>18 years Exclusion Criteria: * use of medication that disrupts acetylcholine metabolism * steroid use * previous gastric or esophageal resection * peritoneal metastases found during surgery * ileostomy **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Randers **Country:** Denmark **Facility:** Regionshospitalet Randers **Zip:** 8930 **Location 2:** **City:** Viborg **Country:** Denmark **Facility:** Regionshospitalet Viborg **Zip:** 8800 **Location 3:** **City:** Eindhoven **Country:** Netherlands **Facility:** Catharina Ziekenhuis **State:** Noord-Brabant **Zip:** 5623EJ **Location 4:** **City:** Veldhoven **Country:** Netherlands **Facility:** Maxima Medical Center **State:** Noord-Brabant **Zip:** 5504DB **Location 5:** **City:** Helmond **Country:** Netherlands **Facility:** Elkerliek Ziekenhuis **Zip:** 5707HA #### Overall Officials **Official 1:** **Affiliation:** Catharina Ziekenhuis Eindhoven **Name:** Misha DP Luyer, MD PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Lubbers T, Luyer MD, de Haan JJ, Hadfoune M, Buurman WA, Greve JW. Lipid-rich enteral nutrition reduces postoperative ileus in rats via activation of cholecystokinin-receptors. Ann Surg. 2009 Mar;249(3):481-7. doi: 10.1097/SLA.0b013e318194d187. **PMID:** 19247038 **Citation:** Luyer MD, Greve JW, Hadfoune M, Jacobs JA, Dejong CH, Buurman WA. Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve. J Exp Med. 2005 Oct 17;202(8):1023-9. doi: 10.1084/jem.20042397. Epub 2005 Oct 10. **PMID:** 16216887 **Citation:** Boelens PG, Heesakkers FF, Luyer MD, van Barneveld KW, de Hingh IH, Nieuwenhuijzen GA, Roos AN, Rutten HJ. Reduction of postoperative ileus by early enteral nutrition in patients undergoing major rectal surgery: prospective, randomized, controlled trial. Ann Surg. 2014 Apr;259(4):649-55. doi: 10.1097/SLA.0000000000000288. **PMID:** 24169163 **Citation:** Lubbers T, Kox M, de Haan JJ, Greve JW, Pompe JC, Ramakers BP, Pickkers P, Buurman WA. Continuous administration of enteral lipid- and protein-rich nutrition limits inflammation in a human endotoxemia model. Crit Care Med. 2013 May;41(5):1258-65. doi: 10.1097/CCM.0b013e31827c0a17. **PMID:** 23388517 **Citation:** Luyer MD, Habes Q, van Hak R, Buurman W. Nutritional stimulation of the autonomic nervous system. World J Gastroenterol. 2011 Sep 14;17(34):3859-63. doi: 10.3748/wjg.v17.i34.3859. **PMID:** 22025873 **Citation:** Luyer MD, Derikx JP, Beyaert R, Hadfoune M, van Kuppevelt TH, Dejong CH, Heineman E, Buurman WA, Greve JW. High-fat nutrition reduces hepatic damage following exposure to bacterial DNA and hemorrhagic shock. J Hepatol. 2009 Feb;50(2):342-50. doi: 10.1016/j.jhep.2008.08.025. Epub 2008 Nov 8. **PMID:** 19070388 **Citation:** Luyer MD, Buurman WA, Hadfoune M, Jacobs JA, Dejong CH, Greve JW. High-fat enteral nutrition reduces endotoxin, tumor necrosis factor-alpha and gut permeability in bile duct-ligated rats subjected to hemorrhagic shock. J Hepatol. 2004 Sep;41(3):377-83. doi: 10.1016/j.jhep.2004.04.026. **PMID:** 15336439 **Citation:** Luyer MD, Jacobs JA, Vreugdenhil AC, Hadfoune M, Dejong CH, Buurman WA, Greve JW. Enteral administration of high-fat nutrition before and directly after hemorrhagic shock reduces endotoxemia and bacterial translocation. Ann Surg. 2004 Feb;239(2):257-64. doi: 10.1097/01.sla.0000108695.60059.80. **PMID:** 14745335 **Citation:** Peters EG, Smeets BJJ, Nors J, Back CM, Funder JA, Sommer T, Laurberg S, Love US, Leclercq WKG, Slooter GD, de Vries Reilingh TS, Wegdam JA, Nieuwenhuijzen GAP, Hiligsmann M, Buise MP, Buurman WA, de Jonge WJ, Rutten HJT, Luyer MDP. Perioperative lipid-enriched enteral nutrition versus standard care in patients undergoing elective colorectal surgery (SANICS II): a multicentre, double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol. 2018 Apr;3(4):242-251. doi: 10.1016/S2468-1253(18)30031-1. Epub 2018 Feb 14. **PMID:** 29426699 **Citation:** Peters EG, De Jonge WJ, Smeets BJ, Luyer MD. The contribution of mast cells to postoperative ileus in experimental and clinical studies. Neurogastroenterol Motil. 2015 Jun;27(6):743-9. doi: 10.1111/nmo.12579. **PMID:** 26011782 **Citation:** Peters EG, Smeets BJ, Dekkers M, Buise MD, de Jonge WJ, Slooter GD, Reilingh TS, Wegdam JA, Nieuwenhuijzen GA, Rutten HJ, de Hingh IH, Hiligsmann M, Buurman WA, Luyer MD. The effects of stimulation of the autonomic nervous system via perioperative nutrition on postoperative ileus and anastomotic leakage following colorectal surgery (SANICS II trial): a study protocol for a double-blind randomized controlled trial. Trials. 2015 Jan 27;16:20. doi: 10.1186/s13063-014-0532-x. **PMID:** 25623276 ## Document Section ### Large Document Module #### Large Docs - Date: 2015-03-04 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 237197 - Type Abbrev: Prot_SAP - Upload Date: 2019-08-14T10:41 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011183 - Term: Postoperative Complications - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M25585 - Name: Ileus - Relevance: LOW - As Found: Unknown - ID: M28891 - Name: Anastomotic Leak - Relevance: HIGH - As Found: Anastomotic Leak - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000057868 - Term: Anastomotic Leak ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Standard **Deaths Num Affected:** 7 **Deaths Num At Risk:** 133 **Description:** standard of care **ID:** EG000 **Other Num Affected:** 22 **Other Num at Risk:** 133 **Serious Number Affected:** 52 **Serious Number At Risk:** 133 **Title:** Standard **Group ID:** EG001 **Title:** Enriched Enteral Nutrition **Deaths Num Affected:** 4 **Deaths Num At Risk:** 132 **Description:** enriched enteral tube feeding **ID:** EG001 **Other Num Affected:** 16 **Other Num at Risk:** 132 **Serious Number Affected:** 55 **Serious Number At Risk:** 132 **Title:** Enriched Enteral Nutrition **Frequency Threshold:** 5 #### Other Events **Term:** clavien dindo grade 1 **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** clavien dindo grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions **Organ System:** Surgical and medical procedures **Source Vocabulary:** #### Serious Events **Term:** anastomotic leakage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 12 **Num At Risk:** 133 **Group ID:** EG001 **Num Affected:** 11 **Num At Risk:** 132 **Term:** remaining serious adverse events **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** serious adverse events according to the official definition in the study protocol, not including the patients with anastomotic leakage **Organ System:** Surgical and medical procedures ##### Stats **Group ID:** EG000 **Num Affected:** 40 **Num At Risk:** 133 **Group ID:** EG001 **Num Affected:** 44 **Num At Risk:** 132 **Time Frame:** 3 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Units:** Participants ### Group **ID:** BG000 **Title:** Standard **Description:** standard of care standard: standard of care ### Group **ID:** BG001 **Title:** Enriched Enteral Nutrition **Description:** enriched enteral tube feeding 1.5ml/ minute perioperative enriched enteral nutrition: enriched enteral tube feeding perioperative ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 63 **Upper Limit:** 74 **Value:** 68 #### Measurement **Group ID:** BG001 **Lower Limit:** 62 **Upper Limit:** 75 **Value:** 69 #### Measurement **Group ID:** BG002 **Lower Limit:** 63 **Upper Limit:** 68 **Value:** 68 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 55 #### Measurement **Group ID:** BG001 **Value:** 52 #### Measurement **Group ID:** BG002 **Value:** 107 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 78 #### Measurement **Group ID:** BG001 **Value:** 80 #### Measurement **Group ID:** BG002 **Value:** 158 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Class Title:** ### Measure #### Measurement **Group ID:** BG002 **Value:** 0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 101 #### Measurement **Group ID:** BG001 **Value:** 103 #### Measurement **Group ID:** BG002 **Value:** 204 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Class Title:** Netherlands #### Measurement **Group ID:** BG000 **Value:** 32 #### Measurement **Group ID:** BG001 **Value:** 29 #### Measurement **Group ID:** BG002 **Value:** 61 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Class Title:** Denmark ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 24 **Upper Limit:** 29.3 **Value:** 26 #### Measurement **Group ID:** BG001 **Lower Limit:** 23.2 **Upper Limit:** 29 **Value:** 25.8 #### Measurement **Group ID:** BG002 **Lower Limit:** 23.7 **Upper Limit:** 29.1 **Value:** 25.8 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 17 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 31 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 92 #### Measurement **Group ID:** BG001 **Value:** 100 #### Measurement **Group ID:** BG002 **Value:** 192 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 20 #### Measurement **Group ID:** BG001 **Value:** 27 #### Measurement **Group ID:** BG002 **Value:** 47 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 132 **Group ID:** BG002 **Value:** 265 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **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 **Population Description:** Race and Ethnicity were not collected from any participant. **Title:** Race and Ethnicity Not Collected **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 5 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** BMI **Unit of Measure:** kg/m^2 ### Measure 6 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** smoking currently **Unit of Measure:** Participants ### Measure 7 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** use of alcohol currently **Unit of Measure:** Participants ### Measure 8 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** use of neoadjuvant therapy for resection **Unit of Measure:** Participants **Population Description:** in both arms, 140 patients participated. in the standard arm 7 patients had to quit the study because exclusion criteria were met, in the enriched enteral nutrition 8 patients had to quit the study because exclusion criteria were met, which is stated in the results participant flow. ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** Catharina Hospital **Phone:** +31402399111 **Title:** dr Misha Luyer ## 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 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 37 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **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:** -45.9 - **Spread:** - **Upper Limit:** -9.2 - **Value:** -32.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -46.6 - **Spread:** - **Upper Limit:** -9.8 - **Value:** -31.4 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 7 - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 9 - **Value:** 5 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 99 - **Spread:** - **Upper Limit:** 220 - **Value:** 150 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 108 - **Spread:** - **Upper Limit:** 227 - **Value:** 164 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 37 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 75 - **Spread:** - **Upper Limit:** 85 - **Value:** 83 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 67 - **Spread:** - **Upper Limit:** 83 - **Value:** 78 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** number of patients with absence of flatus or stool passage and inability to tolerate a regular oral diet between surgery and postoperative day 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** up to 3 weeks after surgery **Title:** Number of Patients Developing Postoperative Ileus **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition #### Outcome Measure 2 **Description:** number of patients developing anastomotic leakage **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** up to 6 weeks after surgery **Title:** Anastomotic Leakage **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition #### Outcome Measure 3 **Description:** number of patients developing aspiration pneumonia **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** up to 3 week after surgery **Title:** Aspiration Pneumonia **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition #### Outcome Measure 4 **Description:** Percent change in Gastric Antral Area, assessed by Ultrasound of the Gastric Antrum Following a Standardized Meal **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** not every patients was fit to have the standard meal or ultrasound, therefore less antral measurements were executed. **Reporting Status:** POSTED **Time Frame:** 3 days after surgery **Title:** Gastric Motility **Type:** SECONDARY **Unit of Measure:** percentage of decrease in antral area ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition #### Outcome Measure 5 **Description:** Length of functional recovery in days, Functional recovery was defined as postoperative patients not receiving intravenous fluid who have adequate pain control, restoration ofindependent mobility, sufficient caloric intake, and no signs of active infection **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** up to 6 weeks after surgery **Title:** Functional Recovery **Type:** SECONDARY **Unit of Measure:** days ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition #### Outcome Measure 6 **Description:** the inflammatory response measured systemically (in blood): C-reactive protein (CRP) **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** up to 48 hours after surgery **Title:** C-reactive Protein (CRP) **Type:** SECONDARY **Unit of Measure:** mg/L ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition #### Outcome Measure 7 **Description:** number of patients needing additional surgical, radiological or endoscopic interventions: All surgical complications are classified using the Clavien-Dindo classification. patients with a Clavien Dindo grade IIIa, IIIb, IVa, IVb, V complication had a surgical, radiological or endoscopic intervention. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** up to 6 weeks after surgery **Title:** Number of Patients Needing Additional Surgical, Radiological or Endoscopic Interventions **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition #### Outcome Measure 8 **Description:** number of patients needing ICU admission after surgery **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** up to 6 weeks after surgery **Title:** Number of Patients Needing ICU Admission **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition #### Outcome Measure 9 **Description:** Global Quality of life on a scale ranging from 0 to 100, with higher scores indicating higher level of functioning. The EORTC QLQ C-30 questionnaires are used **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** 6 months after surgery **Title:** Health-related Quality of Life **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** standard of care **ID:** OG000 **Title:** Standard ##### Group **Description:** enriched enteral tube feeding **ID:** OG001 **Title:** Enriched Enteral Nutrition ### Participant Flow Module #### Group **Description:** standard of care **ID:** FG000 **Title:** Standard #### Group **Description:** enriched enteral tube feeding 1.5ml/ minute perioperative **ID:** FG001 **Title:** Enriched Enteral Nutrition #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 140 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 140 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 133 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 132 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 7 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 8 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01493479 **Acronym:** FIZZ **Brief Title:** Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy as an Initial Therapy of Follicular Lymphoma **Official Title:** Phase II Study of Fractionated 90Y Ibritumomab Tiuxetan (Zevalin) #### Organization Study ID Info **ID:** 06_DOG05_33 #### Organization **Class:** OTHER **Full Name:** The Christie NHS Foundation Trust ### Status Module #### Completion Date **Date:** 2015-11-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-10-15 **Type:** ACTUAL **Last Update Submit Date:** 2019-10-11 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-01 **Type:** ACTUAL #### Start Date **Date:** 2007-06-06 **Type:** ACTUAL **Status Verified Date:** 2019-10 #### Study First Post Date **Date:** 2011-12-16 **Type:** ESTIMATED **Study First Submit Date:** 2011-12-14 **Study First Submit QC Date:** 2011-12-15 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Bayer #### Lead Sponsor **Class:** OTHER **Name:** The Christie NHS Foundation Trust #### Responsible Party **Investigator Affiliation:** The Christie NHS Foundation Trust **Investigator Full Name:** Emmie Taylor **Investigator Title:** Lead Clinical Trial Manager **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** 90Y Ibritumomab tiuxetan (zevalin) has demonstrated consistently high response rates in patients who have received previous treatment for lymphoma. More than two-thirds of the patients who achieve CR go on to experience durable remissions lasting for years. Despite these highly promising clinical results with radioimmunotherapy (RIT) in relapsed follicular lymphoma there is very little data using RIT in previously untreated follicular lymphoma. The objective of this trial is to evaluate the safety and efficacy of two fractions of Zevalin in patients with previously untreated follicular lymphoma in a Phase II study. ### Conditions Module **Conditions:** - Follicular Lymphoma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 76 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: 90Y Ibritumomab tiuxetan - Drug: Rituximab **Label:** Fractionated Initial Zevalin **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Fractionated Initial Zevalin **Description:** 2 x iv infusions of 11.1 MBq/kg. 1st infusion at week 1, 2nd during weeks 9-13. 2nd infusion may be reduced to 7.4MBq/kg in the case of grade 3 haematological toxicity following the 1st infusion. **Name:** 90Y Ibritumomab tiuxetan **Other Names:** - Zevalin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Fractionated Initial Zevalin **Description:** All patients receive 2 x iv infusions of 250 mg/m2 Rituximab given 7-8 days apart prior to each zevalin infusion. The 2nd rituximab infusion is given immediately prior to Zevalin. In addition patients with greater than 20% bone marrow involvement at screening receive rituximab pretreatment prior to entering the main treatment phase of the trial, consisting of 4 x weekly iv doses of rituximab(375 mg/m2). This is followed by a repeat bone marrow biopsy, bone marrow involvement must have fallen to \<= 20% to enter the main treatment phase of the trial. **Name:** Rituximab **Other Names:** - Mabthera **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999. **Measure:** Overall response rate **Time Frame:** Assessed 3 months post treatment **Description:** According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999. **Measure:** Combined Complete Response rate **Time Frame:** Assessed 3 months post treatment **Description:** According to Cheson criteria to standardize response for non-Hodgkin's lymphoma, 1999. **Measure:** Partial Response Rate **Time Frame:** Assessed 3 months post treatment #### Secondary Outcomes **Measure:** Time to disease progression **Time Frame:** Assessed 3 months post treatment, repeated assessment up to 5 years follow-up **Description:** To be assessed for patients achieving a response, including assessment of overall survival and time until next treatment. **Measure:** Response duration **Time Frame:** Assessed 3 months post treatment, repeated assessment up to 5 years follow-up ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients must have a histologically confirmed CD20 +ve follicular lymphoma grades I to IIIa. * Patients with at least one of the following symptoms requiring initiation of treatment: (as outlined by the modified BNLI/GELF criteria below) * Nodal mass \> 7cm in its greater diameter * B symptoms * Elevated serum LDH or beta2-microglobulin * involvement of at least 3 nodal sites (each with a diameter \> 3 cm) * symptomatic splenic enlargement * compressive syndrome * Patients must have an ECOG performance status less than or equal to 2 and an anticipated survival of at least 6 months. * Patients must have an absolute granulocyte count of above 1,500/mm3, and a platelet count of above 100,000/mm3 post 4 weeks of unlabelled Rituximab. A hemoglobin \>= 8.0 g/dl * Patients must have adequate renal function (defined as calculated creatinine clearance \> 30 ml/mn), hepatic function (defined as total bilirubin \<1.5 times upper limit of normal), and hepatic transaminases (defined as AST \<5 times upper limit of normal) * Patients must have given informed consent prior to study entry. Exclusion Criteria: * Patients with a mean of \>20% of the intratrabecular marrow space involved with lymphoma on bone marrow biopsy following induction Rituximab therapy. * Transformed follicular lymphoma and discordant lymphoma * Patients with active obstructive hydronephrosis. * Patients with initial disease bulk greater than 10cm. * Patients with evidence of active infection requiring i.v. antibiotics at the time of study entry. * Patients with congestive heart failure stage III or IV of NYHA classification, myocardial infraction or unstable angina within 6 months or other serious illness that would preclude evaluation. * Patients with left VEF \< 40% * Patients with large pleural or peritoneal effusions. * Patients with known HIV infection or active HBV (HbsAg positivity) or HCV infection. * Known Hypersensitivity to murine antibodies or proteins * Patients who are pregnant or breast-feeding. Male and female patients must agree to use effective contraception for 12 months following 90Y-ibritumomab tiuxetan antibody therapy. * Patients with prior malignancy other than lymphoma, except for adequately-treated skin cancer, cervical cancer in situ, or other cancer for which the patient has been disease-free for 5 years. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Lille **Country:** France **Facility:** Centre Hospitalier Universitaire de Lille **Location 2:** **City:** Nantes **Country:** France **Facility:** Centre Hospitalier Universitaire de Nantes **Location 3:** **City:** Rouen **Country:** France **Facility:** Centre Henri Becquerel **Location 4:** **City:** London **Country:** United Kingdom **Facility:** St George's Hospital **Location 5:** **City:** Manchester **Country:** United Kingdom **Facility:** The Christie NHS Foundation Trust **Zip:** M20 4BX **Location 6:** **City:** Poole **Country:** United Kingdom **Facility:** Poole Hospital NHS Foundation Trust **Location 7:** **City:** Southampton **Country:** United Kingdom **Facility:** Southampton University Hospital #### Overall Officials **Official 1:** **Affiliation:** The Christie NHS Foundation Trust **Name:** Timothy Illidge, Prof **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Illidge TM, Mayes S, Pettengell R, Bates AT, Bayne M, Radford JA, Ryder WD, Le Gouill S, Jardin F, Tipping J, Zivanovic M, Kraeber-Bodere F, Bardies M, Bodet-Milin C, Malek E, Huglo D, Morschhauser F. Fractionated (9)(0)Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. J Clin Oncol. 2014 Jan 20;32(3):212-8. doi: 10.1200/JCO.2013.50.3110. Epub 2013 Dec 2. **PMID:** 24297953 ## 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: M11221 - Name: Lymphoma, Follicular - Relevance: HIGH - As Found: Follicular 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: LOW - As Found: Unknown - ID: T2361 - Name: Follicular Lymphoma - Relevance: HIGH - As Found: Follicular lymphoma ### Condition Browse Module - Meshes - ID: D000008223 - Term: Lymphoma - ID: D000008224 - Term: Lymphoma, Follicular ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic 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: M373 - Name: Rituximab - Relevance: HIGH - As Found: Healthy - ID: M1346 - Name: Antineoplastic Agents, Immunological - 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: D000069283 - Term: Rituximab ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04349579 **Brief Title:** Evaluation of the Effects of Irrigation of the Extraction Socket With Rifamycine **Official Title:** Evaluation of the Effects of Irrigation of the Extraction Socket With Rifamycine on Postoperative Pain, Edema and Trismus in Impacted Lower Third Molar Surgery #### Organization Study ID Info **ID:** 19.07.2017/07 #### Organization **Class:** OTHER **Full Name:** Yuzuncu Yıl University ### Status Module #### Completion Date **Date:** 2023-12-15 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-22 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-20 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-12-15 **Type:** ESTIMATED #### Start Date **Date:** 2018-11-15 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2020-04-16 **Type:** ACTUAL **Study First Submit Date:** 2020-04-12 **Study First Submit QC Date:** 2020-04-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Yuzuncu Yıl University #### Responsible Party **Investigator Affiliation:** Yuzuncu Yıl University **Investigator Full Name:** levent Cigerim **Investigator Title:** Head of Oral and Maxillofacial Surgery Department **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Removal of impacted lower third molar teeth is one of the most common oral surgical procedures, and these operations often lead to various complications in patients. Antibiotics, analgesics and mouthwashes are prescribed for the treatment of complications encountered. When using postoperative antibiotics in surgery of impacted third molar teeth, lower surgical area infection, pain, swelling and trismus are seen. Based on this information, in this study, it is aimed to evaluate the effects of rifamycine intraoperatively on the postoperative pain, swelling and trismus. ### Conditions Module **Conditions:** - Impacted Third Molar Tooth **Keywords:** - rifamycine - pain - edema - trismus ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** FACTORIAL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 35 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Rifamycine is a broad spectrum semi-synthetic antibiotic that acts on gram-positive and gram-negative microorganisms. As a local application, it has areas of use in dentistry such as washing fistula mouths, maxillary sinus and abscess wounds and treating osteomyelitis. **Intervention Names:** - Drug: Rifamycine **Label:** Rifamycine **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Saline, also known as saline solution, is a mixture of sodium chloride in water and has a number of uses in medicine. Applied to the affected area it is used to clean wounds. It is also used to dilute other drugs to be injected and to wash the operation site in dental surgery operations. It is most commonly used as a sterile 9 g of salt per litre (0.9%) solution, known as normal saline. **Intervention Names:** - Drug: Saline Solution **Label:** Saline **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Rifamycine **Description:** Local anesthesia was obtained using 2 ml articaine hydrochloride 40 mg/ml with epinephrine 0.01 mg/ml . The horizontal incision was made with no. 15 scalpel blade and a full thickness mucoperiosteal flap was raised. In all surgical procedures, bone removal and/or tooth sectioning were performed under sterile saline irrigation. Following the extraction, granulation tissues were removed, and bleeding was controlled. Finally, extraction socket was irrigated with the solution which contains 250 mg rifamycine and the mucoperiosteal flap was repositioned by 3.0 silk sutures. **Name:** Rifamycine **Other Names:** - RIF 250 MG IM Ampul **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Saline **Description:** Local anesthesia was obtained using 2 ml articaine hydrochloride 40 mg/ml with epinephrine 0.01 mg/ml . The horizontal incision was made with no. 15 scalpel blade and a full thickness mucoperiosteal flap was raised. In all surgical procedures, bone removal and/or tooth sectioning were performed under sterile saline irrigation. Following the extraction, granulation tissues were removed, and post extraction cavity was irrigated with saline solution. After the bleeding was controlled, the mucoperiosteal flap was repositioned by 3.0 silk sutures. **Name:** Saline Solution **Other Names:** - KANFLEKS % 0,9 IZOTONIK SODYUM KLORUR **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Patients were requested to mark their pain intensity on a pain assessment form using a visual analoge scale (VAS) ranging between 0 (no pain) to 10 (most severe pain). **Measure:** Postoperative Pain **Time Frame:** Postoperatif 1st day **Description:** Patients were requested to mark their pain intensity on a pain assessment form using a visual analoge scale (VAS) ranging between 0 (no pain) to 10 (most severe pain). **Measure:** Postoperative Pain **Time Frame:** Postoperatif 2nd day **Description:** Postoperative swelling was evaluated by the distance between predetermined facial anatomic landmarks (from the mandibular angle to lateral corner of the eye, base of the nose, labial commissura, and soft tissue pogonion) which was measured with using thread and millimeter ruler. **Measure:** Postoperative Swelling **Time Frame:** Postoperative 2nd day **Description:** Postoperative trismus was evaluated by the maximum distance between the incisive borders of the upper and lower right incisive teeth which was measured with a caliper. **Measure:** Postoperative Trismus **Time Frame:** Postoperative 2nd day **Description:** Patients were requested to mark their pain intensity on a pain assessment form using a visual analoge scale (VAS) ranging between 0 (no pain) to 10 (most severe pain). **Measure:** Postoperative Pain **Time Frame:** Postoperatif 3th day **Description:** Patients were requested to mark their pain intensity on a pain assessment form using a visual analoge scale (VAS) ranging between 0 (no pain) to 10 (most severe pain). **Measure:** Postoperative Pain **Time Frame:** Postoperatif 4th day **Description:** Patients were requested to mark their pain intensity on a pain assessment form using a visual analoge scale (VAS) ranging between 0 (no pain) to 10 (most severe pain). **Measure:** Postoperative Pain **Time Frame:** Postoperatif 5th day **Description:** Patients were requested to mark their pain intensity on a pain assessment form using a visual analoge scale (VAS) ranging between 0 (no pain) to 10 (most severe pain). **Measure:** Postoperative Pain **Time Frame:** Postoperatif 6th day **Description:** Patients were requested to mark their pain intensity on a pain assessment form using a visual analoge scale (VAS) ranging between 0 (no pain) to 10 (most severe pain). **Measure:** Postoperative Pain **Time Frame:** Postoperatif 7th day **Description:** Postoperative swelling was evaluated by the distance between predetermined facial anatomic landmarks (from the mandibular angle to lateral corner of the eye, base of the nose, labial commissura, and soft tissue pogonion) which was measured with using thread and millimeter ruler. **Measure:** Postoperative Swelling **Time Frame:** Postoperative 7th day **Description:** Postoperative trismus was evaluated by the maximum distance between the incisive borders of the upper and lower right incisive teeth which was measured with a caliper. **Measure:** Postoperative Trismus **Time Frame:** Postoperative 7th day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * absence of any systemic disease * having bilateral impacted mandibular third molar teeth in a similar position * absence of allergy to any of the drugs used in the study, * absence of pregnancy/lactating state, * no history of any medication use during at least 2 week before the operation. Exclusion Criteria: * not regularly coming to the controls, * not using their medicines regularly * using any additional medication that may affect the outcome of the study **Maximum Age:** 35 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Van **Country:** Turkey **Facility:** Van Yuzuncu Yil University, Faculty of Dentistry **State:** Tuşba **Zip:** 65080 #### Overall Officials **Official 1:** **Affiliation:** Cairo University **Name:** Serap KESKIN TUNC, PhD **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014076 - Term: Tooth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC07 - Name: Mouth and Tooth Diseases ### Condition Browse Module - Browse Leaves - ID: M13069 - Name: Pain, Postoperative - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M7657 - Name: Edema - Relevance: LOW - As Found: Unknown - ID: M17065 - Name: Trismus - Relevance: LOW - As Found: Unknown - ID: M16850 - Name: Tooth, Impacted - Relevance: HIGH - As Found: Impacted - ID: M16831 - Name: Tooth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014095 - Term: Tooth, Impacted ### Intervention Browse Module - Ancestors - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000018501 - Term: Antirheumatic Agents ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: VaCoAg - Name: Vasoconstrictor Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: ARhu - Name: Antirheumatic Agents ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M5609 - Name: Carticaine - Relevance: LOW - As Found: Unknown - ID: M7992 - Name: Epinephrine - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M30371 - Name: Racepinephrine - Relevance: LOW - As Found: Unknown - ID: M211043 - Name: Epinephryl borate - Relevance: LOW - As Found: Unknown - ID: M15119 - Name: Rifamycins - Relevance: HIGH - As Found: Ortho Tri-Cyclen - ID: M277322 - Name: Rifamycin SV - Relevance: HIGH - As Found: Ortho Tri-Cyclen - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000012294 - Term: Rifamycins - ID: C000023808 - Term: Rifamycin SV ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04291079 **Brief Title:** SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON) **Official Title:** A Phase 1, Open-Label, Dose-Escalation, and Dose-Expansion Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of SRK-181 Alone and in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON) #### Organization Study ID Info **ID:** SRK-181-001 #### Organization **Class:** INDUSTRY **Full Name:** Scholar Rock, Inc. ### Status Module #### Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-11 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-09 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Start Date **Date:** 2020-04-23 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2020-03-02 **Type:** ACTUAL **Study First Submit Date:** 2020-02-25 **Study First Submit QC Date:** 2020-02-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Scholar Rock, Inc. #### 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 multi-center, open-label, Phase 1, first-in-human (FIH), dose-escalation, and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SRK-181 administered alone and in combination with anti-PD-(L)1 therapy in adult patients with locally advanced or metastatic solid tumors. The study is divided into 3 treatment parts (Part A1, Part A2, and Part B) and a Long-Term Extension Phase (LTEP). ### Conditions Module **Conditions:** - Cancer **Keywords:** - Solid Tumor - Metastatic - Melanoma - Urothelial - Non-Small Cell Lung Carcinoma - ccRCC - Head and Neck Squamous Cell Carcinoma ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 112 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Part A1 will determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of SRK-181 as a single agent and will determine the recommended Phase 2 dose (RP2D) of SRK-181 as a single-agent. **Intervention Names:** - Biological: SRK-181 **Label:** Part A1: Dose Escalation **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Part A2 will determine the MTD or MAD of SRK-181 in combination with anti-PD-(L)1 antibody therapy and will determine the RP2D of SRK-181 in combination with anti-PD-(L)1 antibody therapy for use in Part B. **Intervention Names:** - Biological: SRK-181 - Biological: anti-PD-(L)1 antibody therapy **Label:** Part A2: Dose Escalation **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** In Part B, parallel cohorts of patients with Non-Small Cell Lung Cancer (NSCLC), Urothelial Carcinoma (UC), Cutaneous Melanoma (MEL), Clear Cell Renal Cell Carcinoma (ccRCC), Head and Neck Squamous Cell Carcinoma (HNSCC), or other advanced or metastatic solid tumor type that is not NSCLC, UC, MEL, or ccRCC will be enrolled to confirm the tolerability of the RP2D of SRK-181 (determined in Part A2) and to evaluate the anti-tumor activity of SRK-181 in combination with an anti-PD-(L)1 antibody therapy. **Intervention Names:** - Biological: SRK-181 - Biological: anti-PD-(L)1 antibody therapy **Label:** Part B: Dose Expansion **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Patients may continue treatment in a LTEP: * Part A1: Patients may continue treatment with SRK-181 as a single agent at the RP2D in the LTEP following 3 cycles of treatment with SRK-181 as a single agent in Part A1. * Part A2: Patients may continue treatment with SRK-181 at the RP2D in combination with anti-PD-(L)1 antibody therapy in the LTEP following 3 cycles of treatment with SRK-181 in combination with anti-PD-(L)1 antibody therapy in Part A2. * Part B: Patients may continue treatment with SRK-181 in combination with anti-PD-(L)1 antibody therapy following 9 cycles of treatment with SRK-181 in combination with anti-PD-(L)1 antibody therapy in Part B **Intervention Names:** - Biological: SRK-181 - Biological: anti-PD-(L)1 antibody therapy **Label:** Long Term Extension Phase (LTEP) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Long Term Extension Phase (LTEP) - Part A1: Dose Escalation - Part A2: Dose Escalation - Part B: Dose Expansion **Description:** anti-latent TGFβ1 monoclonal antibody **Name:** SRK-181 **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Long Term Extension Phase (LTEP) - Part A2: Dose Escalation - Part B: Dose Expansion **Description:** approved anti-PD-(L)1 antibody therapy for each tumor type **Name:** anti-PD-(L)1 antibody therapy **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Dose limiting toxicities (DLTs), as assessed by the Investigator, but not including toxicities clearly related to disease progression or intercurrent illness **Measure:** Safety and tolerability of single agent SRK-181 **Time Frame:** The first 21 days of study treatment **Description:** Dose limiting toxicities (DLTs), as assessed by the Investigator, but not including toxicities clearly related to disease progression or intercurrent illness **Measure:** Safety and tolerability of SRK-181 in combination with anti-PD-(L)1 antibody therapy **Time Frame:** The first 21 days of study treatment #### Secondary Outcomes **Description:** Maximum drug concentration (Cmax) **Measure:** PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy **Time Frame:** Cycle 1 and Cycle 3 (each cycle is 21 days) **Description:** Time to Cmax (Tmax) **Measure:** PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy **Time Frame:** Cycle 1 and Cycle 3 (each cycle is 21 days) **Description:** Last validated plasma concentration (Clast) **Measure:** PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy **Time Frame:** Cycle 1 and Cycle 3 (each cycle is 21 days) **Description:** Time to Clast (Tlast) **Measure:** PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy **Time Frame:** Cycle 1 and Cycle 3 (each cycle is 21 days) **Description:** Half-life (t1/2) **Measure:** PK of SRK-181 alone and in combination with anti-PD-(L)1 antibody therapy **Time Frame:** Cycle 1 and Cycle 3 (each cycle is 21 days) **Description:** Objective response, defined as a CR or PR, as determined by RECIST v1.1 or iRECIST v1.1 **Measure:** Anti-tumor activity of SRK-181, alone or in combination wit anti-PD-(L)1 antibody therapy as potential indicators of clinical response **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Key Inclusion Criteria: * Patient has a histologically documented solid tumor that is metastatic or locally advanced, for which SoC therapy does not exist, has failed in the patient, or is not tolerated by the patient, or for which the patient has been assessed by the Investigator as not being a suitable candidate or otherwise ineligible for the SoC therapy. * For Part A2: o Patient must have a history of anti-PD-(L)1 antibody nonresponse presenting (based upon the Investigator's assessment) either as progressive disease or stable disease (e.g., not improving, but also not worsening, clinically or radiographically) after at least 3 cycles of treatment with the most recent anti-PD-(L)1 antibody therapy (alone or in combination with chemotherapy) approved for that tumor type. (Note: if the duration of prior anti-PD-1 therapy is shorter than 3 cycles and the reason for discontinuation is progressive disease, the progression should be associated with clinical deterioration.) * For Part B Cohort NSCLC, UC, MEL and ccRCC: * Patient must be diagnosed with one of the following disease-specific solid tumors of NSCLC, UC, or MEL, and must have a history of primary nonresponse to anti-PD-1 therapy (alone or in combination with other therapy), presenting the best response (based upon the Investigator's assessment) either as progressive disease or stable disease (e.g., not improving, but also not worsening, clinically or radiographically) after at least 3 cycles of treatment. * For Cohort NSCLC, patients who have genomic tumor aberrations for which a targeted therapy is available (e.g., anaplastic lymphoma kinase, EGFR) must have progressed on an approved therapy for these aberrations or did not tolerate an approved therapy for these aberrations, or were not considered suitable candidates/ were otherwise ineligible for an approved therapy for these aberrations. * For Cohort ccRCC, patients must have a histologically confirmed diagnosis of RCC with a predominant clear cell component and must have received at least 1 prior line of anti-PD-1 treatment (alone or in combination with other therapy) and have had disease progression clinically or radiographically on the most recent anti-PD-1 treatment * Up to 3 lines of treatment are allowed between the last dose of anti-PD-1 and enrollment. * For Part B Cohort HNSCC: * Patients must have a histologically confirmed diagnosis of recurrent or metastatic HNSCC that is non-amendable to curative therapy (e.g., radiation or surgery). * The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible. * Patients must have received one prior line of anti-PD-1 treatment (alone or in combination with other therapy) and have had disease progression clinically or radiographically on the anti-PD-1 treatment. * Up to one line of treatment are allowed between the last dose of anti-PD-1 and enrollment. * For patients with primary oropharyngeal cancer, patients must have results from testing of human papillomavirus (HPV) or P16 status. * For Part B Cohort Any Other (enrollment complete): Patient must be diagnosed with any other solid tumor type that is not NSCLC, UC, MEL, or ccRCC for which the patient has had a history of primary anti PD (L)1 antibody nonresponse, presenting the best response (based upon the Investigator's assessment) as progressive disease, after prior anti-PD-(L)1 antibody therapy (alone or in combination with other therapy) currently approved for that tumor indication * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed at Screening. * Patient must have an Eastern Cooperative Oncology Group performance status (PS) 0-1. * Patient must have a predicted life expectancy of ≥ 3 months. * Women of child-bearing potential (WOCBP) must have a negative urine or serum pregnancy test up to 24 hours prior to first dose of SRK-181. * WOCBP and males with female partners of childbearing potential must agree to use adequate birth control throughout their participation and for 90 days following the last dose of SRK-181. Key Exclusion Criteria: * For Part A1 only: * Patient has had anti-PD-(L)1 antibody therapy ≤ 28 days prior to the first dose of SRK-181. * Patient is receiving concurrent anti-cancer treatment, including anti-PD-(L)1 antibody therapy, either approved or investigational, within 28 days prior to the first dose of SRK-181. * For Part A2 and Part B only: * Patient is receiving concurrent anti-cancer treatment, with the exception of an anti-PD-(L)1 antibody therapy for Part A2 or Part B, either approved or investigational, within 28 days prior to the first dose of SRK-181. * Patient has received biologic therapy (except for anti-PD-(L)1 antibody therapy for Part A2 or Part B), \<28 days prior to the first dose of SRK-181. * Patient has received systemic cytotoxic chemotherapy (except for in combination with anti-PD-(L)1 antibody therapy) \<28 days prior to the first dose of SRK-181. * Patient has received targeted small molecule therapy within 5 half-lives of the compound prior to the first dose of SRK-181. * Patient has a history of intolerance or treatment discontinuation due to severe irAE or other adverse reaction from prior anti-PD-(L)1 antibody therapy. * Patient has a hypersensitivity to anti-PD-(L)1 antibody therapy. * Patient has the documented presence of neutralizing ADA to anti-PD-(L)1 antibody therapy. * Patient has a diagnosis of immunodeficiency, either primary or acquired. * Patient is symptomatic or has uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation. * Patient has current second malignancy at other sites (exceptions: adequately treated in situ carcinoma \[e.g., cervical\], non-MEL skin cancer, bilateral synchronous discordant breast cancer, or indolent prostate cancer under observation). A past history of other malignancies is allowed as long as patient has been free of recurrence for ≥ 2 years, or if the patient has been treated with curative intent within the past 2 years and, in the opinion of the Investigator, is unlikely to have a recurrence. * Women who are pregnant or breastfeeding. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Fullerton **Country:** United States **Facility:** St. Jude Crosson Cancer Institute **State:** California **Zip:** 92835 **Location 2:** **City:** La Jolla **Country:** United States **Facility:** University of California - San Diego **State:** California **Zip:** 92093 **Location 3:** **City:** Los Angeles **Country:** United States **Facility:** The Oncology Institute **State:** California **Zip:** 90603 **Location 4:** **City:** Newport Beach **Country:** United States **Facility:** Hoag Memorial Hospital Presbyterian **State:** California **Zip:** 92663 **Location 5:** **City:** Celebration **Country:** United States **Facility:** Advent Health **State:** Florida **Zip:** 34747 **Location 6:** **City:** Hollywood **Country:** United States **Facility:** Memorial Cancer Institute - South Broward Hospital District **State:** Florida **Zip:** 33021 **Location 7:** **City:** Tampa **Country:** United States **Facility:** H. Lee Moffitt Cancer Center& Research Institute **State:** Florida **Zip:** 33612 **Location 8:** **City:** Chicago **Country:** United States **Facility:** University of Chicago **State:** Illinois **Zip:** 60637 **Location 9:** **City:** Fort Wayne **Country:** United States **Facility:** Fort Wayne Medical Oncology and Hematology, Inc **State:** Indiana **Zip:** 46804 **Location 10:** **City:** Boston **Country:** United States **Facility:** Massachusetts General Hospital **State:** Massachusetts **Zip:** 02115 **Location 11:** **City:** Boston **Country:** United States **Facility:** Beth Israel Deaconess Medical Center **State:** Massachusetts **Zip:** 02155 **Location 12:** **City:** Ann Arbor **Country:** United States **Facility:** University of Michigan **State:** Michigan **Zip:** 48109 **Location 13:** **City:** Detroit **Country:** United States **Facility:** Henry Ford Cancer Institute **State:** Michigan **Zip:** 48202 **Location 14:** **City:** Stony Brook **Country:** United States **Facility:** Stony Brook University Cancer Center **State:** New York **Zip:** 11794 **Location 15:** **City:** Nashville **Country:** United States **Facility:** Tennessee Oncology, Sarah Cannon Research Institute **State:** Tennessee **Zip:** 37201 **Location 16:** **City:** Dallas **Country:** United States **Facility:** BUMC Mary Crowley Cancer Research Centers **State:** Texas **Zip:** 75230 **Location 17:** **City:** Houston **Country:** United States **Facility:** The University of Texas - MD Anderson Cancer Center **State:** Texas **Zip:** 77030 **Location 18:** **City:** Milwaukee **Country:** United States **Facility:** Medical College of Wisconsin **State:** Wisconsin **Zip:** 53226 **Location 19:** **City:** Ansan-Si **Country:** Korea, Republic of **Facility:** Korea University Ansan Hospital **Zip:** 92093 **Location 20:** **City:** Seongnam-si **Country:** Korea, Republic of **Facility:** Seoul National University - Bundang Hospital **Zip:** 13620 **Location 21:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Korea University Anam Hospital **Zip:** 02841 **Location 22:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Seoul National University Hospital **Zip:** 03080 #### Overall Officials **Official 1:** **Affiliation:** Scholar Rock, Inc. **Name:** Lu Gan, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### 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 ### 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: LOW - As Found: Unknown - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: M11528 - Name: Melanoma - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - 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: M4225 - Name: Antibodies - Relevance: HIGH - As Found: Program - ID: M4230 - Name: Antibodies, Monoclonal - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000000906 - Term: Antibodies ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00822679 **Brief Title:** Eszopiclone and Inflammatory Mediators in Patients With Acute Coronary Syndrome **Official Title:** Eszopiclone and Inflammatory Mediators in Patients With Acute Coronary Syndrome #### Organization Study ID Info **ID:** HSC# 07-0797-01 #### Organization **Class:** OTHER **Full Name:** University of Arizona ### Status Module #### Completion Date **Date:** 2010-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-12-20 **Type:** ESTIMATED **Last Update Submit Date:** 2016-10-26 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2016-12-20 **Type:** ESTIMATED **Results First Submit Date:** 2016-10-26 **Results First Submit QC Date:** 2016-10-26 #### Start Date **Date:** 2007-10 **Status Verified Date:** 2016-10 #### Study First Post Date **Date:** 2009-01-14 **Type:** ESTIMATED **Study First Submit Date:** 2009-01-12 **Study First Submit QC Date:** 2009-01-13 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Sumitomo Pharma America, Inc. **Class:** FED **Name:** Southern Arizona VA Health Care System #### Lead Sponsor **Class:** OTHER **Name:** University of Arizona #### Responsible Party **Investigator Affiliation:** University of Arizona **Investigator Full Name:** Sairam Parthasarathy **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of the study is to examine the effects of Eszopiclone, a sleep aid, on inflammatory mediators and coagulability in patients with a recent myocardial infarction. **Detailed Description:** Abnormalities of sleep are common in hospitalized patients, but the mechanisms and consequences are not well understood. In many of these patients, sleep is very disrupted, occurs during the daytime, and circadian rhythm is diminished or lost. Hospitalized patients experience more frequent arousals and awakenings than is normal and show decreases in rapid eye movement and slow wave sleep. The degree of sleep fragmentation is at least equivalent to that seen in patients with obstructive sleep apnea. About 20% of arousals and awakenings are related to noise, 10% are related to health care personnel and care-related activities, and the cause for the remainder is not known, although severity of underlying disease is likely an important factor. In studies of sleep following acute myocardial infarction, marked disturbances have been found in patients, whether in the ICU and on the wards. These disturbances include long periods of wakefulness; poor sleep efficiency, and disruption of REM sleep. The fact that there is also a loss in circadian rhythm in these patients may indicate a widespread disruption of bodily homeostasis which, in turn, may be related to the infarct itself, to a more generalized physiological response to stress or to other factors. Sleep disruption can induce sympathetic activation and elevation of blood pressure, which may contribute to patient morbidity. It has been shown that there is an increased level of some inflammatory and coagulation factors in the recovery period following an acute myocardial infarction (MI). Post MI patients have higher levels of TNF-α, IL-6 and tissue plasminogen activator as well as lower levels of antithrombin III and protein C. The aim of this study is to determine whether the sleep-aid Eszopiclone can improve sleep, decrease inflammation, and decrease pro-coagulation factors in patients who have recently suffered myocardial infarction when compared with a control group without sleep aids. Eszopiclone is a benzodiazepine receptor agonist which improves sleep quality by reducing the time to sleep onset and reduces wakefulness during the sleep period. Unlike benzodiazepines, it does not affect the deeper stage 3 and 4 sleep. The result is that it provides a more nearly normal night sleep than other sleep aids. It is hoped that improved sleep patterns will result in more rapid normalization of inflammatory and coagulation factors and perhaps more rapid recovery. ### Conditions Module **Conditions:** - Acute Coronary Syndrome - Sleep Disorder **Keywords:** - Acute Coronary Syndrome - cytokines - pro-coagulant mediators - sleep disorders ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 5 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects receive Eszopiclone for three consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors **Intervention Names:** - Drug: Eszopiclone **Label:** 1: Eszopiclone **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subjects given placebo for 3 consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors **Intervention Names:** - Other: Placebo **Label:** 2: Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1: Eszopiclone **Description:** Subject receives Eszopiclone for 3 consecutive nights. 3 mg orally at bedtime for patients age 64 and under, and 2 mg QHS for patients age 65 and older. **Name:** Eszopiclone **Other Names:** - Lunesta **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 2: Placebo **Description:** Subjects are given placebo for 3 consecutive nights **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Not performed. Zero subjects were randomized. Many potential participants screen-failed. **Measure:** Changes in Circulating Inflammatory Cytokines (Interleukin [IL]-1B, IL-6, IL-10, and Tumor Necrosis Alpha [TNF-α]) and Pro-coagulant Mediators (Soluble P-selectin and CD40 Ligand). **Time Frame:** 2 days #### Secondary Outcomes **Measure:** Changes in Objective and Subjective Measures of Sleep **Time Frame:** 4 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with recent (less than or equal to 8 weeks) "uncomplicated" acute myocardial infarction, can either be ST elevation MI (STEMI) or non-ST elevation MI (non-STEMI) and subsequent to successful treatment (percutaneous revascularization or medical therapy). Exclusion Criteria: * Obstructive sleep apnea (OSA, defined as apnea-hypopnea index \> 15 per hour) or previous diagnosis of OSA. * Patients with life-threatening arrhythmias (such as atrial fibrillation/flutter with hypotension, ventricular tachycardia, or ventricular fibrillation, or significant heart block that requires pacing \[Type III, Type IIb\]), cardiogenic shock, severe heart failure requiring high levels of inspired oxygen (FiO2 \>40%), persistent chest pain despite medical or other interventions, and patients who are considered too unstable to participate for other medical reasons or complications (such as concomitant strokes, retroperitoneal hematoma, gastro-intestinal bleeding). Also excluded are patients with history of cardiac arrest during the same hospitalization. * Unable to take oral medications * Use of other sedative-hypnotics * Hypersensitivity to Eszopiclone or any component of the formulation * Pregnancy **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tucson **Country:** United States **Facility:** Southern Arizona VA Health Care System **State:** Arizona **Zip:** 85723 #### Overall Officials **Official 1:** **Affiliation:** Southern Arizona VA Health Care System **Name:** Sairam Parthasarathy, MD **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 - ID: D000009422 - Term: Nervous System Diseases - ID: D000009461 - Term: Neurologic Manifestations - ID: D000001523 - Term: Mental Disorders ### 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: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - 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: M22242 - Name: Parasomnias - Relevance: HIGH - As Found: Sleep Disorders - ID: M15696 - Name: Sleep Wake Disorders - Relevance: HIGH - As Found: Sleep Disorders - 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: M12404 - Name: Neurologic Manifestations - 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: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012893 - Term: Sleep Wake Disorders - ID: D000020447 - Term: Parasomnias - ID: D000054058 - Term: Acute Coronary Syndrome - ID: D000013577 - Term: Syndrome ### Intervention Browse Module - Ancestors - ID: D000006993 - Term: Hypnotics and Sedatives - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Coag - Name: Coagulants ### Intervention Browse Module - Browse Leaves - ID: M475 - Name: Eszopiclone - Relevance: HIGH - As Found: Invasive Bladder Cancer - ID: M6259 - Name: Coagulants - Relevance: LOW - As Found: Unknown - ID: M10043 - Name: Hypnotics and Sedatives - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069582 - Term: Eszopiclone ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** 1: Eszopiclone **Description:** Subjects receive Eszopiclone for three consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors Eszopiclone: Subject receives Eszopiclone for 3 consecutive nights. 3 mg orally at bedtime for patients age 64 and under, and 2 mg QHS for patients age 65 and older. **ID:** EG000 **Title:** 1: Eszopiclone **Group ID:** EG001 **Title:** 2: Placebo **Description:** Subjects given placebo for 3 consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors Placebo: Subjects are given placebo for 3 consecutive nights **ID:** EG001 **Title:** 2: Placebo **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Units:** Participants ### Group **ID:** BG000 **Title:** 1: Eszopiclone **Description:** Subjects receive Eszopiclone for three consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors Eszopiclone: Subject receives Eszopiclone for 3 consecutive nights. 3 mg orally at bedtime for patients age 64 and under, and 2 mg QHS for patients age 65 and older. ### Group **ID:** BG001 **Title:** 2: Placebo **Description:** Subjects given placebo for 3 consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors Placebo: Subjects are given placebo for 3 consecutive nights ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure **Category Title:** <=18 years **Category Title:** Between 18 and 65 years **Category Title:** >=65 years **Class Title:** ### Measure ### Measure **Category Title:** Female **Category Title:** Male **Class Title:** ### Measure **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Title:** Age, Categorical ### Measure 2 **Title:** Age, Continuous ### Measure 3 **Title:** Gender ### Measure 4 **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement ### Limitations and Caveats **Description:** Zero subjects were randomized. Many potential participants screen-failed. Study was closed due to difficulty with recruitment. ### Point of Contact **Email:** [email protected] **Organization:** University of Arizona **Phone:** 5206266109 **Title:** Sairam Parthasarathy ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 #### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Not performed. Zero subjects were randomized. Many potential participants screen-failed. **Population Description:** Not performed. Zero subjects were randomized. Many potential participants screen-failed. **Reporting Status:** POSTED **Time Frame:** 2 days **Title:** Changes in Circulating Inflammatory Cytokines (Interleukin [IL]-1B, IL-6, IL-10, and Tumor Necrosis Alpha [TNF-α]) and Pro-coagulant Mediators (Soluble P-selectin and CD40 Ligand). **Type:** PRIMARY ##### Group **Description:** Subjects receive Eszopiclone for three consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors Eszopiclone: Subject receives Eszopiclone for 3 consecutive nights. 3 mg orally at bedtime for patients age 64 and under, and 2 mg QHS for patients age 65 and older. **ID:** OG000 **Title:** 1: Eszopiclone ##### Group **Description:** Subjects given placebo for 3 consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors Placebo: Subjects are given placebo for 3 consecutive nights **ID:** OG001 **Title:** 2: Placebo #### Outcome Measure 2 **Reporting Status:** NOT_POSTED **Time Frame:** 4 days **Title:** Changes in Objective and Subjective Measures of Sleep **Type:** SECONDARY ### Participant Flow Module #### Group **Description:** Subjects receive Eszopiclone for three consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors Eszopiclone: Subject receives Eszopiclone for 3 consecutive nights. 3 mg orally at bedtime for patients age 64 and under, and 2 mg QHS for patients age 65 and older. **ID:** FG000 **Title:** 1: Eszopiclone #### Group **Description:** Subjects given placebo for 3 consecutive nights to observe changes in sleep measures, and inflammatory and coagulation factors Placebo: Subjects are given placebo for 3 consecutive nights **ID:** FG001 **Title:** 2: Placebo #### Period **Title:** Overall Study ##### 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 **Recruitment Details:** Potential participants screen failed. There was no subject randomized (n=0). **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01779479 **Brief Title:** Efficacy and Safety of Cabazitaxel Versus Weekly Paclitaxel as Neo-adjuvant Treatment in Patients With Triple Negative or Luminal B/HER2 Normal BC (GENEVIEVE) **Official Title:** Randomized, Open-label, Phase II Study Comparing the Efficacy and the Safety of Cabazitaxel Versus Weekly Paclitaxel Given as Neo-adjuvant Treatment in Patients With Operable Triple Negative or Luminal B/HER2 Normal Breast Cancer (GENEVIEVE) #### Organization Study ID Info **ID:** GBG 74 #### Organization **Class:** OTHER **Full Name:** German Breast Group #### Secondary ID Infos **ID:** 2012-003330-16 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2016-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-08-01 **Type:** ACTUAL **Last Update Submit Date:** 2017-07-31 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-08 **Type:** ACTUAL #### Start Date **Date:** 2013-02 **Status Verified Date:** 2016-02 #### Study First Post Date **Date:** 2013-01-30 **Type:** ESTIMATED **Study First Submit Date:** 2013-01-25 **Study First Submit QC Date:** 2013-01-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** German Breast Group #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Cabazitaxel is a new taxoid which promotes the tubulin assembly in vitro and stabilizes microtubules against cold-induced depolymerization as efficiently as docetaxel and was selected for development based on a better antiproliferative activity on resistant cell lines than docetaxel. It has shown superior survival against mitoxantrone (MTX) plus prednisone in docetaxel pre-treated hormone refractory metastatic prostate cancer patients leading to registration of the compound. It showed a favorable toxicity profile with an interestingly low rate of alopecia. In the Genevieve study it will be compared against weekly paclitaxel which is currently most widely used treatment of breast cancer patients. A head-to-head comparison in the neoadjuvant setting will allow a rapid and precise comparison of efficacy and tolerability of cabacitaxel versus paclitaxel to decide in how far further development of this taxoid in breast cancer is reasonable. **Detailed Description:** Primary Objective To compare the pathologic complete response (pCR) rate in the breast (ypT0/is ypN0/+) in patients with operable Triple Negative or luminal B/HER2 normal breast cancer treated with either cabazitaxel or weekly paclitaxel. Secondary Objective To assess * pCR rates per arm separately for the stratified subpopulations. * Objective response rate (ORR) in the breast according to WHO criteria. * pCR rate defined as ypT0 ypN0. * pCR rate defined as ypT0/is ypN0. * pCR rate in the axillary lymph nodes (ypN0). * To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery. * Breast conservation surgery rate. * To assess the toxicity (NCI CTCAE V4.03) and compliance in both arms. * Invasive loco-regional recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS). * To explore the biomarkers and profiles potentially predicting response to treatment. ### Conditions Module **Conditions:** - Primary Breast Cancer **Keywords:** - German Breast Group - GBG Forschungs GmbH - GBG - GBG 74 - Genevieve - Breast Cancer - Primary Breast Cancer - Cabazitaxel - Paclitaxel - neo-adjuvant - triple negative - luminal B ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 333 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Cabacitaxel **Label:** Cabacitaxel **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Paclitaxel **Label:** Paclitaxel **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Cabacitaxel **Description:** Cabazitaxel 25 mg/m² i.v. (Day 1) every 3 weeks (cycle) as 1-hour i.v infusion for a total of up to 4 cycles over a maximum total treatment period of 15 weeks before surgery **Name:** Cabacitaxel **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Paclitaxel **Description:** Paclitaxel 80 mg/m² as 1-hour i.v infusion. Patients will receive weekly (Days 1, 8, 15) paclitaxel administrations for a maximum of 12 infusions for a maximum of 4 cycles over a maximum total treatment period of 15 weeks before surgery (1 cycle = 3 weeks). **Name:** Paclitaxel **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** pathologic complete response (pCR) rate **Time Frame:** 15 months #### Secondary Outcomes **Description:** pathologic complete response (pCR) rate separately for stratified subpopulations **Measure:** pathologic complete response (pCR) rate separately for subpopulations **Time Frame:** 15 months **Measure:** Objective response rate (ORR) **Time Frame:** 15 months **Measure:** pCR rate defined as ypT0 ypN0 **Time Frame:** 15 months **Measure:** pCR rate defined as ypT0/is ypN0 **Time Frame:** 15 months **Measure:** pCR rate in the axillary lymph nodes (ypN0) **Time Frame:** 15 months **Description:** To determine the pCR rate in patients with a clinical complete response (cCR) and a negative core biopsy before surgery **Measure:** pCR rate in patients with a clinical complete response (cCR) **Time Frame:** 15 months **Description:** To determine the local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery **Measure:** local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) **Time Frame:** 15 months **Measure:** Breast conservation surgery rate **Time Frame:** 15 months **Description:** To assess the toxicity (NCI CTCAE V4.03) in both arms. **Measure:** Toxicity **Time Frame:** 15 months **Description:** To assess compliance in both arms. **Measure:** Compliance **Time Frame:** 15 months **Measure:** Invasive loco-regional recurrence free survival (LRRFS) **Time Frame:** 15 months **Measure:** Distant-disease-free survival (DDFS) **Time Frame:** 15 months **Measure:** Invasive disease-free survival (IDFS) **Time Frame:** 15 months **Measure:** Overall survival (OS) **Time Frame:** 15 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures. * Complete baseline documentation must be sent to GBG Forschungs GmbH. * Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint. * Tumor lesion in the breast with a palpable size of \>= 2 cm or a sonographical size of \>= 1 cm in maximum diameter. The lesion has to be measurable in two dimensions, preferably by sonography. * Patients must be in the following stages of disease: cT3 or cT2 or cT1c and cN+ or cT1c and pNSLN+. * In patients with multifocal or multicentric breast cancer, the largest lesion should be evaluated. * Centrally confirmed triple negative or luminal B/HER2-normal subtype. ER- and PgR-negative defined as \<1% stained cells. HER-2 negative defined as IHC 0+, 1+ or IHC 2+ and FISH/SISH/CISH (ratio \<2.0) negative. Luminal B defined as ER and/or PgR + and \> 14% Ki-67 stained cells. The formalin-fixed, paraffin-embedded (FFPE) breast tissue block from the diagnostic core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization. * Age \>= 18 years. * Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1 (see Appendix A). * Laboratory requirements: Hemoglobin \> 9.0 g/dL, Absolute neutrophil count \> 1.5 x 109/L, Platelet count \> 100 x 109/L, AST/SGOT and/or ALT/SGPT \< 2.5 x ULN; Total bilirubin \< 1.0 x ULN, Serum creatinine \< 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance \< 60 mL/min should be excluded (see Appendix 2 for formula). * Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential. * Complete staging work-up within 3 months prior to randomization. All patients must have bilateral mammography, breast ultrasound (\<= 21 days), breast MRI (optional), chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scan done. In case of positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated. * Patients must be available and compliant for central diagnostics, treatment and follow-up. Exclusion Criteria: * Any prior treatment for primary breast cancer including radiation therapy * History of ipsi/ or contra-lateral invasive breast cancer * Locally advanced disease including N3 and metastatic disease * Patients in the following stages of disease are not allowed: cT4 * Prior malignancy without being disease-free for more than 5 years (except carcinoma in situ of the cervix or other in situ cancer (e.g. bladder cancer) and adequately treated basal cell carcinoma of the skin. * Clinically significant (i.e. active) cardiovascular disease, including cerebrovascular accident (≤6 months before enrolment), myocardial infarction, arterial thrombotic events (≤6 months before enrolment), unstable angina pectoris, New York Heart Association (NYHA) ≥ grade 2 congestive heart failure and/or hypertension, serious cardiac arrhythmia requiring medication during the study and that might interfere with regularity of the study treatment, or not controlled by medication * Any severe acute or chronic medical condition which could impair the ability of the patient to participate to the study or to comply with the study procedures or interfere with interpretation of study results (such as significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures). * Active infection. * Sex hormones. Prior treatment must be stopped before study entry. * Inability and unwillingness to comply with study visits, treatment, testing, and to comply with the protocol. * Administration of any live virus vaccine within 8 weeks preceding study entry. * Use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical trial * Requirement for radiation therapy concurrent with study anticancer treatment. Patients who require breast or chest wall radiation therapy after surgery are eligible * Pregnancy or breastfeeding women * Patients with childbearing potential who do not agree to use accepted and effective method of contraception (barrier methods, intrauterine contraceptive devices, sterilization) during the study treatment period and following a period of 6 months after the last study drug administration. * History of hypersensitivity (grade ≥ 3) to polysorbate 80 or any study drugs or excipients * Concurrent or planned treatment with potent strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a two-week wash-out period is necessary for patients who are already on these treatments) (see Appendix 3) * Contraindications to the use of corticosteroid treatment * Symptomatic peripheral neuropathy grade ≥ 2 (National Cancer Institute Common Terminology Criteria \[NCI CTCAE\] v.4.03). **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Düsseldorf **Country:** Germany **Facility:** Luisenkrankenhaus **Zip:** 40235 #### Overall Officials **Official 1:** **Affiliation:** Luisenkrankenhaus Düsseldorf **Name:** Gunter von Minckwitz, Prof. Dr. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Kummel S, Paepke S, Huober J, Schem C, Untch M, Blohmer JU, Eiermann W, Gerber B, Hanusch C, Hilfrich J, Jackisch C, Schneeweiss A, Denkert C, Engels K, Klare P, Fasching PA, von Minckwitz G, Burchardi N, Loibl S. Randomised, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE). Eur J Cancer. 2017 Oct;84:1-8. doi: 10.1016/j.ejca.2017.06.037. Epub 2017 Jul 30. **PMID:** 28768217 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases ### 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: HIGH - As Found: Breast Cancer - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000972 - Term: Antineoplastic Agents, Phytogenic - ID: D000000970 - Term: Antineoplastic Agents - ID: D000050257 - Term: Tubulin Modulators - ID: D000050256 - Term: Antimitotic Agents - ID: D000050258 - Term: Mitosis Modulators - 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: HIGH - As Found: Surgery - ID: M231 - Name: Albumin-Bound Paclitaxel - Relevance: LOW - As Found: Unknown - ID: M26197 - Name: Tubulin Modulators - Relevance: LOW - As Found: Unknown - ID: M26196 - Name: Antimitotic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000017239 - Term: Paclitaxel ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05793879 **Acronym:** Aphasia360 **Brief Title:** Virtual Reality Training for Aphasia Rehabilitation **Official Title:** Anomias Rehabilitation Training Through 360° Videos #### Organization Study ID Info **ID:** UC #### Organization **Class:** OTHER **Full Name:** Catholic University of the Sacred Heart ### Status Module #### Completion Date **Date:** 2026-03 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-07 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-06 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Start Date **Date:** 2023-05-02 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2023-03-31 **Type:** ACTUAL **Study First Submit Date:** 2023-03-07 **Study First Submit QC Date:** 2023-03-20 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Fondazione Poliambulanza #### Lead Sponsor **Class:** OTHER **Name:** Catholic University of the Sacred Heart #### Responsible Party **Investigator Affiliation:** Catholic University of the Sacred Heart **Investigator Full Name:** Claudia Repetto **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Aphasia is an acquired deficit following acute damage to the central nervous system that involves the difficulty or impossibility of understanding and formulating language. A typical disorder of non-fluent forms of aphasia is anomia. Anomia refers to the difficulty in finding words, in particular when trying to name objects and actions. According to the Embodied Cognition approach (EC), language is tightly connected to the motor system. In this view, language rehabilitation programs should stimulate language through the activation of the motor system. In this approach, since anomic deficits are often due to a weak link between the meaning of the word and its lemma, the Hebbs' principles of coincident and correlated learning can be exploited, i.e., by intensifying the synchronous activation of lexicon and semantics and connecting them with the motor counterpart. In this study, the investigators present an innovative training, based on the EC framework, in which they will make use of new technologies for anomia rehabilitation in post-stroke patients. Specifically, the researchers will use immersive 360° videos representing everyday actions displayed from the first-person point of view, experienced through a head-mounted display. The training will be administered 3 times a week for 4 weeks. The control group will watch standard videos representing the same actions recorded from the third-person perspective. Naming abilities will be tested before and after the training together with other cognitive and psychological measures. The investigators expect that the group who will undergo the 360° video-based training will show greater improvement of performance compared to the control group. ### Conditions Module **Conditions:** - Anomic Aphasia **Keywords:** - virtual reality - embodied cognition - rehabilitation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will watch spherical videos displaying everyday actions towards objects; an audio is embedded describing the action and the object represented (i.e. "I'm cutting the potatoes"). **Intervention Names:** - Behavioral: Video 360 **Label:** Video 360 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients will watch standard videos displaying everyday actions towards objects; an audio is embedded describing the action and the object represented (i.e. "I'm cutting the potatoes") **Intervention Names:** - Behavioral: Standard videos **Label:** Standard video **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Video 360 **Description:** Patients will undergo 12 sessions, 3 per weeks, 4 weeks **Name:** Video 360 **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Standard video **Description:** Patients will undergo 12 sessions, 3 per weeks, 4 weeks **Name:** Standard videos **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** All the trained videos will be presented and the patient will be asked to name the verb and the object depicted. The accuracy will be registered **Measure:** Number of verbs and objects correctly named **Time Frame:** post treatment, 1 month #### Secondary Outcomes **Description:** It is an Italian validated neuropsychological battery aiming at testing all the language abilities. It includes several tests tapping into the different linguistic abilities, but for the purpose of the present study only the verb and object naming subtest will be administered. Higher scores indicate greater naming abilities **Measure:** Batteria per l'Analisi dei Deficit Afasici (BADA), naming subtest **Time Frame:** post treatment, 1 month **Description:** The test consists of 2 sections. The first one is made of 5 questions scored from 1 to 5 points each. The final score ranges from 5 to 15, where the lesser the better. The second section is a visual scale on which the best state the patient can imagine is marked 100 and the worst state is marked 0. **Measure:** EuroQol Health-related quality of life (EQ-5D-3L) **Time Frame:** post treatment, 1 month **Description:** The survey is administered to the caregiver. It includes 32 questions each scored from 1 to 5 points. The final scores ranges from 32 to 160, where higher scores indicate greater communication abilities **Measure:** Functional Outcome Questionnaire (FOQ-A) **Time Frame:** post treatment, 1 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * naming disorder in the post-acute phase (index event occurring at least 6 months earlier) * to have already received rehabilitation treatment in the acute phase * noun naming below cut-off * verbs naming below cut- off Exclusion Criteria: * concomitant or pre-existing (with respect to the index event) neurological and psychiatric deficits * epilepsy * balance disorders * neglect **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:** Claudia Repetto, Prof **Phone:** +39 3488122121 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Alice Cancer, PhD **Role:** CONTACT #### Locations **Location 1:** **City:** Brescia **Contacts:** ***Contact 1:*** - **Name:** Alessandra Maietti, Msc - **Role:** CONTACT **Country:** Italy **Facility:** Poliambulanza **Status:** RECRUITING **Zip:** 25123 #### Overall Officials **Official 1:** **Affiliation:** Catholic University of the Sacred Heart **Name:** Claudia Repetto, Prof **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013064 - Term: Speech Disorders - ID: D000007806 - Term: Language Disorders - ID: D000003147 - Term: Communication Disorders - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M4352 - Name: Aphasia - Relevance: HIGH - As Found: Aphasia - ID: M4175 - Name: Anomia - Relevance: HIGH - As Found: Anomic Aphasia - ID: M15864 - Name: Speech Disorders - Relevance: LOW - As Found: Unknown - ID: M10823 - Name: Language Disorders - Relevance: LOW - As Found: Unknown - ID: M6374 - Name: Communication 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 ### Condition Browse Module - Meshes - ID: D000001037 - Term: Aphasia - ID: D000000849 - Term: Anomia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01714479 **Brief Title:** Skeletal Muscle Response to Amino Acids and Load Carriage Exercise **Official Title:** Skeletal Muscle and Physical Performance Responses to Leucine-Enriched Nutrition Supplementation During Load Carriage #### Organization Study ID Info **ID:** 12-18-HC #### Organization **Class:** FED **Full Name:** United States Army Research Institute of Environmental Medicine ### Status Module #### Completion Date **Date:** 2013-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-07-21 **Type:** ACTUAL **Last Update Submit Date:** 2017-07-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-11 **Type:** ACTUAL #### Start Date **Date:** 2012-10 **Status Verified Date:** 2016-09 #### Study First Post Date **Date:** 2012-10-26 **Type:** ESTIMATED **Study First Submit Date:** 2012-10-23 **Study First Submit QC Date:** 2012-10-25 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** US Army Natick Soldier Research, Development & Engineering Center #### Lead Sponsor **Class:** FED **Name:** United States Army Research Institute of Environmental Medicine #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Warfighters often experience physical overload, as the uniform and associated gear that they carry burdens them with substantial loads. The loads increase energy expenditure to levels that exceed a Warfighter's typical energy intake. The typical assault load is approximately 25 kg, although loads as high as 55 kg are often carried, which when combined with extreme energy expenditures can degrade health and performance, and increase the risk of injury. Branched-chain amino acid (leucine) supplementation may confer protection against the negative effects of operational stress by stimulating muscle protein synthesis and reducing degradation. This study will determine if leucine-enriched nutrition supplementation confers protection against the negative consequences of sustained load carriage exercise, and explore the mechanisms by which leucine might impart protection. ### Conditions Module **Conditions:** - Muscle Loss - Muscle Anabolism - Muscle Performance ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Load Carriage - with a calorie-free placebo **Intervention Names:** - Other: Placebo **Label:** Load Carriage - Control **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** Load Carriage with leucine-enriched amino acid supplementation **Intervention Names:** - Other: Leucine-enriched nutritional supplement **Label:** Load Carriage - leucine-enriched nutrition supplement **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Conventional Exercise with a calorie-free placebo **Intervention Names:** - Other: Placebo **Label:** Conventional Exercise - Control **Type:** PLACEBO_COMPARATOR #### Arm Group 4 **Description:** Conventional Exercise with leucine-enriched Amino Acid supplementation **Intervention Names:** - Other: Leucine-enriched nutritional supplement **Label:** Conventional Exercise - Leucine-enriched Nutrition Supplement **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Conventional Exercise - Leucine-enriched Nutrition Supplement - Load Carriage - leucine-enriched nutrition supplement **Description:** A protein and carbohydrate supplement with high levels of leucine **Name:** Leucine-enriched nutritional supplement **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Conventional Exercise - Control - Load Carriage - Control **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** Change in muscle protein synthesis and whole-body protein turnover during and after load carriage or conventional exercise with or without amino acid supplementation **Time Frame:** 90 min exercise bout (exercise) and 180 min of recovery #### Secondary Outcomes **Measure:** Changes in muscle performance in recovery from load carriage or conventional exercise with or without amino acid supplementation **Time Frame:** 4, 24, 48, and 72 hours post exercise ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Weight stable (±5 lbs)with a body mass index between 22-29 kg/m2 and a VO2peak of 40 - 60 ml/kg/min * Willing to refrain from taking any NSAIDS (i.e., aspirin, Advil®, Aleve®, Naprosyn®), or any aspirin-containing products, alchohol, and nicotine * Females must be on oral contraception Exclusion Criteria: * Metabolic or cardiovascular abnormalities, gastrointestinal disorders * Disease or medication that affects macronutrient metabolism or the ability to participate in strenuous exercise * Allergies or intolerance to foods (e.g. lactose intolerance/milk allergy), vegetarian practices, or medications (including, but not limited to, lidocaine or phenylalanine) to be used in the study * Anemia (HCT \<38) and Sickle Cell Anemia/Trait, abnormal PT/PTT test or problems with blood clotting * Present condition of alcoholism, use of nutritional/sports supplements, anabolic steroids, or other substance abuse issues * Musculoskeletal injuries that compromise the ability to exercise * Blood donation within 8 weeks of enrollment * Pregnancy and women not on oral contraceptives **Healthy Volunteers:** True **Maximum Age:** 39 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Natick **Country:** United States **Facility:** US Army Research Institute of Environmental Medicine **State:** Massachusetts **Zip:** 01760 #### Overall Officials **Official 1:** **Affiliation:** United States Army Research Institute of Environmental Medicine **Name:** Stefan M Pasiakos, Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Margolis LM, McClung HL, Murphy NE, Carrigan CT, Pasiakos SM. Skeletal Muscle myomiR Are Differentially Expressed by Endurance Exercise Mode and Combined Essential Amino Acid and Carbohydrate Supplementation. Front Physiol. 2017 Mar 23;8:182. doi: 10.3389/fphys.2017.00182. eCollection 2017. **PMID:** 28386239 **Citation:** Pasiakos SM, McClung HL, Margolis LM, Murphy NE, Lin GG, Hydren JR, Young AJ. Human Muscle Protein Synthetic Responses during Weight-Bearing and Non-Weight-Bearing Exercise: A Comparative Study of Exercise Modes and Recovery Nutrition. PLoS One. 2015 Oct 16;10(10):e0140863. doi: 10.1371/journal.pone.0140863. eCollection 2015. **PMID:** 26474292 **Citation:** Margolis LM, Murphy NE, Carrigan CT, McClung HL, Pasiakos SM. Ingesting a Combined Carbohydrate and Essential Amino Acid Supplement Compared to a Non-Nutritive Placebo Blunts Mitochondrial Biogenesis-Related Gene Expression after Aerobic Exercise. Curr Dev Nutr. 2017 May 23;1(6):e000893. doi: 10.3945/cdn.117.000893. eCollection 2017 Jun. **PMID:** 29955707 ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: AA - Name: Amino Acids - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T10 - Name: Leucine - Relevance: HIGH - As Found: Cleared by ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05110079 **Brief Title:** Revascularization of Total or Sub-total Occluded Peripheral Arteries With ByCross® Device. Post Market Clinical Followup **Official Title:** Revascularization of Total or Sub-total Occluded Peripheral Arterial Vessels With ByCross #### Organization Study ID Info **ID:** QA 366-02 #### Organization **Class:** INDUSTRY **Full Name:** Taryag Medical Ltd. ### Status Module #### Completion Date **Date:** 2023-03-31 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2022-10-21 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-20 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-06-02 **Type:** ACTUAL **Status Verified Date:** 2021-10 #### Study First Post Date **Date:** 2021-11-05 **Type:** ACTUAL **Study First Submit Date:** 2021-10-26 **Study First Submit QC Date:** 2021-10-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Taryag Medical 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:** Post market clinical follow up of Bycross® device. **Detailed Description:** A prospective, multi-center, non-randomized, observational, post market clinical follow-up study of the ByCross® device to evaluate the safety, technical performance and effectiveness of the ByCross® device and effectiveness of the procedure using the device and adjunctive therapy. The ByCross® is a single use, disposable, minimal invasive aspiration rotational atherectomy device. The ByCross® is aimed to enable effective revascularization and restore blood flow in peripheral occluded vessels. In cases that the artery is completely blocked such that opening is not possible with currently available solutions and the procedure cannot be completed, the device is capable of crossing the blocked lesion without guiding wire and enables the completion of the procedure in a safe and effective manner, thus potentially eliminating the need for open bypass surgery. The ByCross® can be used in several pathologies: calcified atheroma, old and fresh thrombus and in stent restenosis at peripheral arteries including iliac ### Conditions Module **Conditions:** - Peripheral Arterial Disease ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 75 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** After assessment of the lesion by angiography the ByCross is advanced over a 0.035" guidewire through a sheath to the occlusion. Activation will rotate the shaft and start aspiration. Under fluoroscopy the ByCross is advanced continuously over the wire. in case passage with guidewire is not possible the ByCross tip is advanced into the occlusion for 10mm, then wire is advanced to check is passage is possible, this is repeated until passage by the wire is achieved. At harder lesion the speed is set to high. Once the occlusion is crossed the ByCross tip is enlarged, device is advanced once more to increase opening. Additional adjunctive treatment may be performed per physician's discretion and according to standard of care. Performance criteria of the complete procedure is to achieved more than 70% opening. **Name:** ByCross Atherectomy and Thrombectomy **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Passage of the occlusion by the BYCROSS® device and post atherectomy residual stenosis ≤ 50% relative to reference diameter to allow for angioplasty and/or stenting if required, and complete procedural success of residual stenosis ≤ 30% **Measure:** Acute procedure success **Time Frame:** Up to 8 hours post-procedure **Description:** Freedom, at any period between procedure and 90 days post procedure from device related Serious Adverse Events (SADEs) defined by the site as part of the normal reporting practice **Measure:** Freedom from device related serious adverse events **Time Frame:** 90 days follow up #### Secondary Outcomes **Description:** Rate of cases of vascular treatment in the same vessel treated during the study **Measure:** Rate of Target vessel revascularization (TVR) at 12 months **Time Frame:** 12 months **Description:** Rate of cases of vascular re-intervention of the same lesion treated during the study **Measure:** Rate of Target lesion revascularization (TLR) at 12 months **Time Frame:** 12 months **Description:** Improvement in Rutherford classification compared to pre-procedure **Measure:** Rutherford classification improvement at 12 months **Time Frame:** 12 months **Description:** Rate of amputation of the limb treated during the study **Measure:** Rate of amputations of at 12 months **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subject has documented symptomatic chronic peripheral vascular disease at a vessel below the aorta bifurcation * Candidate for percutaneous intervention * Severely stenotic occlusion target vessel (stenosis ≥70%) * Subject has been informed on the nature of the study and has provided informed consent * Subject is capable of meeting study requirements including presences at follow-up visits Exclusion Criteria: * Patient anatomy excludes use of BYCROSS® device * Vessels of the cardiopulmonary, coronary or cerebral circulations * Undersized vessel diameters (\<3mm) * Perforation of the vessel distally or proximally to the occlusion segment prior atherectomy * Subintimal position of the guiding catheter or the guidewire * Use in stents or stent grafts if the guidewire has become threaded at any point in the wire mesh of stent or stent graft or the lining of the stent graft * Target is at vessel segment which includes tortuous course with radius of curvature \<= 40mm * Access pathway includes tortuous course with radius of curvature \<= 25mm, in specific extremely sharp aortic bifurcation * In aneurysmatically altered iliac vessel segments * If the introducer sheath, the guide catheter, the guidewire or the BYCROSS® sustains any visible damage, especially kinking * In the fracture areas of broken stents * Known or suspected allergy to any of the components of the system or to a medicinal product to be administered in connection with the planned procedure * Persistent vasospasm * During use of a defibrillator on the patient **Maximum Age:** 100 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Adult subjects (male and female) with limb ischemia requiring treatment and target vessel stenosis ≥ 70% ### Contacts Locations Module #### Locations **Location 1:** **City:** Arnsberg **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Simone Muller - **Phone:** +49 2932 952-244826 - **Role:** CONTACT ***Contact 2:*** - **Name:** Michael Lichtenberg, M.D. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Germany **Facility:** Karolinen-Hospital, Klinik für Angiologie **Status:** RECRUITING **Zip:** 59755 **Location 2:** **City:** Heidelberg **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ilka Buss - **Phone:** +49 6221 56-37920 - **Role:** CONTACT ***Contact 2:*** - **Name:** Christian Erbel, M.D. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Germany **Facility:** Universitätsklinikum Heidelberg **Status:** RECRUITING **Zip:** 69120 **Location 3:** **City:** Lingen **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Daniela Viehweider - **Phone:** 0591 910-6121 - **Role:** CONTACT ***Contact 2:*** - **Name:** Joerg Tessarek, M.D. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Germany **Facility:** Bonifatius Hospital Lingen **Status:** RECRUITING **Zip:** 49808 #### Overall Officials **Official 1:** **Affiliation:** Bonifatius Hospital Lingen **Name:** Joerg Tessarek, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000050197 - Term: Atherosclerosis - ID: D000001161 - Term: Arteriosclerosis - ID: D000001157 - Term: Arterial Occlusive Diseases - ID: D000014652 - Term: Vascular 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: M29213 - Name: Peripheral Arterial Disease - Relevance: HIGH - As Found: Peripheral Arterial Disease - ID: M18894 - Name: Peripheral Vascular Diseases - Relevance: HIGH - As Found: Peripheral Arterial Disease - ID: M17400 - Name: 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 ### Condition Browse Module - Meshes - ID: D000058729 - Term: Peripheral Arterial Disease - ID: D000016491 - Term: Peripheral Vascular Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02494479 **Brief Title:** Efficacy and Safety of Prurisol Administered Orally for Active Mild to Moderate Chronic Plaque Psoriasis **Official Title:** A Randomized, Double Blind, Parallel Group, Placebo Controlled Clinical Study of the Efficacy and Safety of Three Different Daily Dosages of Prurisol Administered Orally to Subjects With Active Mild to Moderate Chronic Plaque Psoriasis #### Organization Study ID Info **ID:** CTIX-PRU-004 #### Organization **Class:** INDUSTRY **Full Name:** Cellceutix Corporation ### Status Module #### Completion Date **Date:** 2016-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-07-19 **Type:** ACTUAL **Last Update Submit Date:** 2017-07-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-04 **Type:** ACTUAL #### Start Date **Date:** 2015-08 **Status Verified Date:** 2016-05 #### Study First Post Date **Date:** 2015-07-10 **Type:** ESTIMATED **Study First Submit Date:** 2015-06-26 **Study First Submit QC Date:** 2015-07-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Cellceutix Corporation #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is designed to evaluate the efficacy and safety of Prurisol using three different oral daily dose regimens administered to subjects with active mild to moderate chronic plaque psoriasis. **Detailed Description:** The total duration of study participation for an individual subject is approximately 112 days (16 weeks) consisting of a Screening visit, followed within 21 days by Randomization and a Treatment Period of 84 days, and a Follow-up Period of 28 days after the last day of study drug treatment. A window of ± 3 days will be considered acceptable for conduct of each scheduled visit following the first visit. This study will require eight (8) scheduled subject visits: x Visit 1: Screening (Up to Day 21) x Visit 2: Baseline (Day 0) x Visit 3: Day 14 Interim (± 3 days) x Visit 4: Day 28 Interim (± 3 days) x Visit 5: Day 42 Interim (± 3 days) x Visit 6: Day 56 Interim (± 3 days) x Visit 7: Day 84 End of Treatment/Unscheduled/ET (± 3 days) x Visit 8: Day 112 Follow-up (± 3 days) ### Conditions Module **Conditions:** - Plaque Psoriasis **Keywords:** - Psoriasis - Topical Psoriasis - Mild Psoriasis - Moderate Psoriasis - Active Psoriasis - Plaque Psoriasis - Skin Diseases ### 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:** 115 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** One (1) 50 mg tablet of Prurisol and one (1) matching placebo tablet given AM and two (2) matching placebo tablets given PM for 84 (± 3) days **Intervention Names:** - Drug: Prurisol **Label:** 50mg of Purisol daily **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** One (1) 50 mg tablets of Prurisol and one (1) matching placebo tablet given twice daily (AM and PM) for 84 (± 3) days **Intervention Names:** - Drug: Prurisol **Label:** 100mg of Purisol daily **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Two (2) 50 mg tablets of Prurisol given twice daily (AM and PM) for 84 (± 3) days **Intervention Names:** - Drug: Prurisol **Label:** 200mg of Purisol daily **Type:** ACTIVE_COMPARATOR #### Arm Group 4 **Description:** Two (2) placebo tablets given twice daily (AM and PM) for 84 (± 3) days **Intervention Names:** - Drug: Placebo **Label:** Placebo daily **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 100mg of Purisol daily - 200mg of Purisol daily - 50mg of Purisol daily **Description:** 50mg tablet **Name:** Prurisol **Other Names:** - Purisol, 50mg tablet **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo daily **Description:** Sugar pill designed to match Purisol tablet **Name:** Placebo **Other Names:** - Matching Placebo to Purisol tablet **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** The primary efficacy endpoint will be the percentage of subjects with ≥ 2 point improvement in IGA rating as defined by visual inspections of patient lesions **Time Frame:** 84 days #### Secondary Outcomes **Measure:** The Secondary efficacy endpoints are the percentage of subjects in each treatment group with:≥ 2 point improvement in IGA at 28 days **Time Frame:** 28 days **Measure:** The Secondary efficacy endpoints are the percentage of subjects in each treatment group with: ≥ 2 point improvement in IGA at 56 days **Time Frame:** 56 Days **Measure:** The Secondary efficacy endpoints are the percentage of subjects in each treatment group with: ≥1 point improvement in Scaling Score of Target Lesion at 28 days **Time Frame:** 28 Days **Measure:** The Secondary efficacy endpoints are the percentage of subjects in each treatment group with: ≥1 point improvement in Scaling Score of Target Lesion at 56 days **Time Frame:** 56 Days **Measure:** The Secondary efficacy endpoints are the percentage of subjects in each treatment group with: ≥1 point improvement in Scaling Score of Target Lesion at 84 days **Time Frame:** 84 Days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or non-pregnant female adults aged 18 years with a clinical diagnosis of stable (at least 6 months) plaque psoriasis, not including scalp or intertriginous areas. * The extent of psoriasis must meet all of the following three (3) criteria: * Total Body Surface Area (BSA) affected by plaque psoriasis of 10% to 20% inclusive * Investigator's Global Assessment (IGA) score of the severity of psoriasis of 2 or 3 (5- point ordinal scale) * Identification of a target psoriatic lesion with a score of 3 on the Target Lesion Assessment scale (5-point ordinal scale) for Scaling. (Other psoriatic lesions may have lower scaling scores.) * Females of reproductive potential must not be pregnant * Female subjects with reproductive potential, if sexually active, must agree to use reliable means of contraception * The subject must agree to avoid prolonged exposure to the sun and avoid the use of tanning booths or other ultraviolet light sources during the study. * The subject must provide signed and dated written informed consent to participate in the clinical study. Exclusion Criteria: * 1. Females of reproductive potential who are not using reliable contraception. * Presence of any non-psoriatic uncontrolled (in the Investigator's medical opinion) systemic disease. i * Unstable forms of psoriasis, e.g. guttate, erythrodermic, exfoliative, palmoplantar, nail, or pustular. * Use within 6 months of biologic treatment for psoriasis * Use within 24 months of chemotherapy or radiation therapy. * Use within 2 months of any systemic immunosuppressive therapy. * Use within 1 month of (1) systemic corticosteroids, (2) systemic antibiotics, (3) systemic antipsoriasis treatments (e.g. methotrexate, corticosporin, hydroxyurea), (4) PUVA therapy, (5) UVB, (6) systemic anti-inflammatory treatment. * Use within 2 weeks of topical antipsoriasis drugs or topical corticosteroids or topical retinoids. * Presence of a condition (e.g., history of frequent consumption of substantial quantities of alcohol, or an untreated psychiatric condition) that makes it unlikely that the requirements of the protocol will be completed. * History of any previous use of a Tumor Necrosis Factor (TNF) blocker or other immunomodulating drug as therapy for psoriasis within the 6 months prior to screening. * History of any allergic reaction to any formulation of abacavir. * Previous treatment with any abacavir-containing product, e.g., Ziagen®, Epzicom®, or Trizivir®. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Huntsville **Country:** United States **Facility:** Cellceutix Study Center **State:** Alabama **Zip:** 35801 **Location 2:** **City:** Encino **Country:** United States **Facility:** Cellceutix Study Center **State:** California **Zip:** 91436 **Location 3:** **City:** Coral Gables **Country:** United States **Facility:** Cellceutix Study Center **State:** Florida **Zip:** 33134 **Location 4:** **City:** Hialeah **Country:** United States **Facility:** Cellceutix Study Center **State:** Florida **Zip:** 33016 **Location 5:** **City:** Kissimmee **Country:** United States **Facility:** Cellceutix Study Center **State:** Florida **Zip:** 34741 **Location 6:** **City:** Miami **Country:** United States **Facility:** Cellceutix Study Center **State:** Florida **Zip:** 33126 **Location 7:** **City:** Miami **Country:** United States **Facility:** Cellceutix Study Center **State:** Florida **Zip:** 33144 **Location 8:** **City:** Pembroke Pines **Country:** United States **Facility:** Cellceutix Study Center **State:** Florida **Zip:** 33026 **Location 9:** **City:** Las Vegas **Country:** United States **Facility:** Cellceutix Study Center **State:** Nevada **Zip:** 89119 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000017444 - Term: Skin Diseases, Papulosquamous - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14422 - Name: Psoriasis - Relevance: HIGH - As Found: Psoriasis - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M19713 - Name: Skin Diseases, Papulosquamous - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011565 - Term: Psoriasis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03810079 **Brief Title:** Closed-loop tDCS in Patients in Minimally Conscious State **Official Title:** Closed-loop Application of tDCS to Promote Responsiveness of Patients in MCS #### Organization Study ID Info **ID:** 2015/251 #### Organization **Class:** OTHER **Full Name:** University of Liege ### Status Module #### Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-26 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Start Date **Date:** 2019-08-01 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2019-01-18 **Type:** ACTUAL **Study First Submit Date:** 2019-01-11 **Study First Submit QC Date:** 2019-01-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Liege #### Responsible Party **Investigator Affiliation:** University of Liege **Investigator Full Name:** Aurore Thibaut **Investigator Title:** PhD **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 will test a closed-loop system using EEG-arousal measures (spectral entropy) to define the best moment of the day for application of transcranial direct current stimulation (tDCS) in patients in MCS This study aims at answering the following questions: 1. Is tDCS applied during high vigilance states more effective in increasing the level of conscious awareness than low vigilance states in patients in minimally conscious state (MCS)? 2. Is the EEG pattern (connectivity, complexity) different after application of active or sham tDCS at high vigilance or low vigilance states? 3. Is there a difference in the profile of tDCS-responders as compared to non-responders with regards to etiology, clinical diagnosis (MCS+/MCS-), age, gender, time post-injury, functional outcome, structural and functional neuroimaging findings and EEG markers? **Detailed Description:** During the last 20 years, with the rediscovering and development of noninvasive brain stimulation (NIBS); techniques such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have flourished thanks to the advancements in functional imaging, elegant neurophysiological assessments, computer generated modeling, and most importantly, the groundwork of well-designed research methodology. TDCS represents a safe, inexpensive and straightforward technique that could be easily integrated in rehabilitation programs. In a first sham-controlled double-blind randomized crossover study, the effect of a single prefrontal tDCS was evaluated in a heterogeneous population of patients with disorders of consciousness (DOC), vegetative state (VS) and minimally conscious state (MCS), acute-subacute (\< 3months) and chronic, with traumatic or non-traumatic etiologies. At the individual level, tDCS responders were defined as patients who presented a new sign of consciousness (e.g., command following; visual pursuit; recognition, manipulation or localization of objects); after the active tDCS session, that was not present before nor during the sham tDCS session. 13/30 patients in MCS showed a tDCS-related improvement. 2 acute (\<3 months) patients in VS out of 25 showed a tDCS response (i.e. showed command following and visual pursuit present after the anodal stimulation not present at baseline or pre- or post- sham-tDCS). At group level, a treatment effect, as measured by the Coma Recovery Scale-Revised (CRS-R) was observed in the MCS but not in the VS patients' group. In addition, no tDCS related side effects were observed. In another sham-controlled study tDCS was applied for five days either over the primary motor cortex or over the left prefrontal cortex in 10 chronic patients with DOC. In this trial, the effect of tDCS have been assessed up to 12 months post stimulation. This study highlighted that even chronic patients in DOC could improve and the effect could last up to 12 months post tDCS. Several tDCS studies have been performed by the Coma Science Group (Dr Thibaut) and other groups. So far, a total of 221 patients with DOC have been included in eight studies without any serious adverse event. In addition, three other trials performed by Naro et al including a total of 59, did not report any adverse event either. Therefore, tDCS appears as a safe technique, especially when applied by experts and highly trained investigators with a strong background in both non-invasive brain stimulation and patients with disorders of consciousness. From a neurophysiological point of view, tDCS increases the neuronal excitability by facilitating the action potential release and modification of the excitability of NMDA receptors. Moreover, tDCS may strengthen task-related dynamical synaptic connections. The effect of a single tDCS session last about 60 to 90 min. While, when the stimulation is repeated for 10 to 20 sessions, the effects have been found to last up to 3 months after the end of the stimulation sessions. A major challenge in the application of tDCS to patients with DOC is the variability in the individual behavioral response. Indeed, in previous studies conducted by the Coma Science Group and other groups, the rate of responders was inconsistent across studies. As stated above, a responder is a patient who showed a new sign of consciousness following the application of active tDCS that was never observed beforehand nor before or after sham stimulation. However, given the specificity of crossover designs used in these studies, this definition was recently updated as a patient who showed a new sign of consciousness for the first time after the application of active tDCS. The next steps to optimize the applications of tDCS include a better identification of tDCS responders beforehand. To that end, Thibaut and colleagues conducted a retrospective study comparing the structural and metabolic neuroimagery profiles of patients who responded to tDCS (n=8) and patients who did not (n=13), by the means of structural MRI T1 data and 18-fluorodeoxyglucose position emission tomography. The results showed a greater atrophy in non-responders in regions including the left DLPFC, the medial-prefrontal cortex and the left thalamus as compared to responders. The same areas as well as the thalamus were hypometabolic in non-responders as compared to responders. This suggest that response to tDCS requires at least partial structural and metabolic preservation of the stimulated area, as well as in subcortical brains areas involved in attention and working memory. Later, the authors used the same sample and retrospectively analyzed resting state EEG brain connectivity. The results showed higher theta centrality in responders (as compared to non-responders) meaning this new biomarker can be used to predict tDCS response in patients with DOC (Thibaut et al. 2018). Another key component to responsiveness is the timing of the stimulations. Indeed, patients with DOC typically present fluctuations in vigilance impacting their responsiveness to any kind of external stimuli. Patients in MCS even show a periodicity of 70 minutes in these fluctuations (range 57-80), comparable to the fluctuations in attention observed in healthy controls, while patient in VS do not present this type of periodicity. Piarulli and colleagues used the spectral entropy measured with resting EEG to highlight the periodicity in its fluctuations and suggested that the EEG spectral entropy variability in MCS could mirror the fluctuation of awareness previously described in this population. Administering tDCS during specific time windows (i.e., periods of low or high arousal) could therefore influence its clinical efficacy in patients in MCS since it is known that the positive effects of tDCS are dependent on the brain neural state. To this end, recent advances in information technology enable the implementation of a closed-loop set-up by complex computations being performed in real-time. Using this technology to target specific levels of vigilance with tDCS in patient in MCS could provide insight in understanding the patterns of responding to that treatment and optimize future applications. ### Conditions Module **Conditions:** - Minimally Conscious State **Keywords:** - transcranial direct current stimulation - minimally conscious state - disorders of consciousness - non invasive brain stimulation - neuromodulation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Randomized double-blind sham-controlled crossover ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 16 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will undergo continuous 20 channels EEG and receive anodal tDCS (bilateral prefrontal stimulation) at a pre-determined high level of EEG-derived spectral entropy during 20 minutes followed by a clinical assessment (Coma Recovery Scale-Revised) **Intervention Names:** - Device: Anodal transcranial direct current stimulation **Label:** Anodal tDCS High Vigilance **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Patients will undergo continuous 20 channels EEG and receive anodal tDCS (bilateral prefrontal stimulation) at a pre-determined low level of EEG-derived spectral entropy during 20 minutes followed by a clinical assessment (Coma Recovery Scale-Revised) **Intervention Names:** - Device: Anodal transcranial direct current stimulation **Label:** Anodal tDCS Low Vigilance **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Patients will undergo continuous 20 channels EEG and receive tDCS (bilateral prefrontal stimulation) at a random level of EEG-derived spectral entropy during 20 minutes followed by a clinical assessment (Coma Recovery Scale-Revised) **Intervention Names:** - Device: Anodal transcranial direct current stimulation **Label:** Anodal tDCS Random Vigilance **Type:** SHAM_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Anodal tDCS High Vigilance - Anodal tDCS Low Vigilance - Anodal tDCS Random Vigilance **Description:** Neuromodulation of bilateral prefrontal areas using 2 mA tDCS delivered during 20 minutes via sponge electrodes on the scalp **Name:** Anodal transcranial direct current stimulation **Other Names:** - Anodal tDCS **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** 20 channels EEG will be continuously recorded to identify potential cortical changes induced by the stimulation. **Measure:** Change in EEG **Time Frame:** It will be measured throughout the 6 hour session and reported over the course of about 3 weeks #### Secondary Outcomes **Description:** Coma Recovery Scale-Revised (CRS-R- will be performed before and after tDCS (anodal and sham). **Measure:** Change in the CRS-R total score **Time Frame:** It will be measured at the beginning of the 6 hour session for 30 minutes, at the end of the 6 hour session for 30 minutes and reported over the course of about 3 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * CNS medication stable for at least a week, * Stable diagnosis of MCS (no diagnosis change based on 2 CRS-R performed within 1 week). * Adult (16 years old - 75 years old) * \> 28 days post injury Exclusion Criteria: * open craniotomies, * VPS under the stimulated area (prefrontal cortex), * pacemaker, * metallic cerebral implant, according to safety criteria for transcranial electric stimulation, * severe medical conditions that might influence clinical diagnosis and EEG activity (e.g., severe hepatic insufficiency or renal failure, or sub-continuous or abundant epileptiform discharges on standard EEG recordings). **Maximum Age:** 75 Years **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Liege **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Aurore Thibaut, PhD - **Phone:** 003243668069 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Alice Barra, MSc - **Phone:** 003243668069 - **Role:** CONTACT **Country:** Belgium **Facility:** University Hospital of Liege **Status:** RECRUITING **Zip:** 4000 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001925 - Term: Brain Damage, Chronic - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014474 - Term: Unconsciousness - ID: D000003244 - Term: Consciousness Disorders - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M6468 - Name: Consciousness Disorders - Relevance: LOW - As Found: Unknown - ID: M20567 - Name: Persistent Vegetative State - Relevance: HIGH - As Found: Minimally Conscious State - ID: M5207 - Name: Brain Injuries - Relevance: LOW - As Found: Unknown - ID: M5202 - Name: Brain Damage, Chronic - 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: M17224 - Name: Unconsciousness - 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: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000018458 - Term: Persistent Vegetative State ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04025879 **Brief Title:** A Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Removal and Adjuvant Treatment With Nivolumab or Placebo for Participants With Surgically Removable Early Stage Non-small Cell Lung Cancer **Official Title:** A Phase 3, Randomized, Double-blind Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Resection and Adjuvant Treatment With Nivolumab or Placebo for Participants With Resectable Stage II-IIIB Non-small Cell Lung Cancer #### Organization Study ID Info **ID:** CA209-77T #### Organization **Class:** INDUSTRY **Full Name:** Bristol-Myers Squibb #### Secondary ID Infos **ID:** 2019-000262-38 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2024-09-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-08 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-05 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-07-26 **Type:** ACTUAL #### Start Date **Date:** 2019-11-05 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2019-07-19 **Type:** ACTUAL **Study First Submit Date:** 2019-07-17 **Study First Submit QC Date:** 2019-07-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Bristol-Myers Squibb #### 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 main purpose of the study is to examine if periadjuvant (neoadjuvant, then adjuvant) immunotherapy will prolong event free survival in participants with early stage non-small cell lung cancer. ### Conditions Module **Conditions:** - Carcinoma, Non-Small-Cell Lung ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 482 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Biological: Nivolumab - Drug: Carboplatin - Drug: Cisplatin - Drug: Paclitaxel - Drug: Pemetrexed - Drug: Docetaxel **Label:** Neoadj. Nivo+ Pt-based Doublet Chemo followed by Adj. Nivo **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Carboplatin - Drug: Cisplatin - Drug: Paclitaxel - Drug: Pemetrexed - Drug: Placebo - Drug: Docetaxel **Label:** Neoadj. Plac. + Pt-based Doublet Chemo followed by Adj.Plac. **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Neoadj. Nivo+ Pt-based Doublet Chemo followed by Adj. Nivo **Description:** Specified dose on specified days **Name:** Nivolumab **Other Names:** - Opdivo, BMS936558 **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Neoadj. Nivo+ Pt-based Doublet Chemo followed by Adj. Nivo - Neoadj. Plac. + Pt-based Doublet Chemo followed by Adj.Plac. **Description:** Specified dose on specified days **Name:** Carboplatin **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Neoadj. Nivo+ Pt-based Doublet Chemo followed by Adj. Nivo - Neoadj. Plac. + Pt-based Doublet Chemo followed by Adj.Plac. **Description:** Specified dose on specified days **Name:** Cisplatin **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Neoadj. Nivo+ Pt-based Doublet Chemo followed by Adj. Nivo - Neoadj. Plac. + Pt-based Doublet Chemo followed by Adj.Plac. **Description:** Specified dose on specified days **Name:** Paclitaxel **Type:** DRUG #### Intervention 5 **Arm Group Labels:** - Neoadj. Nivo+ Pt-based Doublet Chemo followed by Adj. Nivo - Neoadj. Plac. + Pt-based Doublet Chemo followed by Adj.Plac. **Description:** Specified dose on specified days **Name:** Pemetrexed **Type:** DRUG #### Intervention 6 **Arm Group Labels:** - Neoadj. Plac. + Pt-based Doublet Chemo followed by Adj.Plac. **Description:** Specified dose on specified days **Name:** Placebo **Type:** DRUG #### Intervention 7 **Arm Group Labels:** - Neoadj. Nivo+ Pt-based Doublet Chemo followed by Adj. Nivo - Neoadj. Plac. + Pt-based Doublet Chemo followed by Adj.Plac. **Description:** Specified dose on specified days **Name:** Docetaxel **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Event-Free Survival (EFS) as Assessed by Blinded Independent Central Review (BICR) **Time Frame:** 5 Years from randomization #### Secondary Outcomes **Measure:** Overall Survival (OS) **Time Frame:** Up to 5 years from randomization **Measure:** Pathologic Complete Response (pCR) Rate as Assessed by Blinded Independent Pathology Review (BIPR) **Time Frame:** At the time of surgery, between week 12 to week 18 **Measure:** Major Pathological Response (MPR) Rate as Assessed by Blinded Independent Pathology Review **Time Frame:** Up to 8 weeks following completion of neoadjuvant surgery, approximately study week 22 **Measure:** Incidence of Serious Adverse Events (SAEs) **Time Frame:** Up to 80 weeks **Measure:** Incidence of Adverse Events (AEs) **Time Frame:** Up to 80 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Participants with suspected or histologically confirmed Stage IIA (\> 4 cm) to IIIB (T3N2) non-small cell lung carcinoma (NSCLC) with disease that is considered resectable * No brain metastasis * Treatment-naive for NSCLC (no prior systemic anti-cancer treatment) * Ability to provide surgical or biopsy tumor tissue for biomarkers * Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 Exclusion Criteria: * Participants with an active, known or suspected autoimmune disease * Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) * Any previous anti-cancer treatment including cytotoxic, IO treatment, targeted agents, or radiotherapy for NSCLC * Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol-defined inclusion/exclusion criteria apply **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tampa **Country:** United States **Facility:** Local Institution - 0104 **State:** Florida **Zip:** 33612 **Location 2:** **City:** Atlanta **Country:** United States **Facility:** Local Institution - 0040 **State:** Georgia **Zip:** 30342 **Location 3:** **City:** Augusta **Country:** United States **Facility:** Local Institution - 0120 **State:** Georgia **Zip:** 30912 **Location 4:** **City:** Chicago **Country:** United States **Facility:** Local Institution - 0145 **State:** Illinois **Zip:** 60611 **Location 5:** **City:** Chicago **Country:** United States **Facility:** Local Institution - 0078 **State:** Illinois **Zip:** 60612 **Location 6:** **City:** Orland Park **Country:** United States **Facility:** Local Institution - 0121 **State:** Illinois **Zip:** 60462 **Location 7:** **City:** Bethesda **Country:** United States **Facility:** Rcca Md Llc **State:** Maryland **Zip:** 20817 **Location 8:** **City:** Boston **Country:** United States **Facility:** Local Institution - 0074 **State:** Massachusetts **Zip:** 02215 **Location 9:** **City:** Boston **Country:** United States **Facility:** Local Institution - 0076 **State:** Massachusetts **Zip:** 02215 **Location 10:** **City:** Traverse City **Country:** United States **Facility:** Local Institution - 0086 **State:** Michigan **Zip:** 49684 **Location 11:** **City:** Lebanon **Country:** United States **Facility:** Local Institution - 0100 **State:** New Hampshire **Zip:** 03756 **Location 12:** **City:** Cincinnati **Country:** United States **Facility:** Local Institution - 0055 **State:** Ohio **Zip:** 45220 **Location 13:** **City:** Cleveland **Country:** United States **Facility:** Local Institution - 0102 **State:** Ohio **Zip:** 44106 **Location 14:** **City:** Houston **Country:** United States **Facility:** Local Institution - 0054 **State:** Texas **Zip:** 77030 **Location 15:** **City:** Fredericksburg **Country:** United States **Facility:** Local Institution - 0103 **State:** Virginia **Zip:** 22408 **Location 16:** **City:** Ciudad Autonoma Beunos Aires **Country:** Argentina **Facility:** Local Institution - 0032 **State:** Buenos Aires **Zip:** 1431 **Location 17:** **City:** ABB **Country:** Argentina **Facility:** Local Institution - 0031 **State:** Ciudad Autónoma De Buenos Aires **Zip:** C1199ABB **Location 18:** **City:** Buenos Aires **Country:** Argentina **Facility:** Local Institution - 0043 **Zip:** CP1280AEB **Location 19:** **City:** Caba **Country:** Argentina **Facility:** Local Institution - 0030 **Zip:** 1426 **Location 20:** **City:** Sydney **Country:** Australia **Facility:** Local Institution - 0020 **State:** New South Wales **Zip:** 2050 **Location 21:** **City:** Heidelberg **Country:** Australia **Facility:** Local Institution - 0033 **State:** Victoria **Zip:** 3084 **Location 22:** **City:** Melbourne **Country:** Australia **Facility:** Local Institution - 0122 **State:** Victoria **Zip:** 3065 **Location 23:** **City:** North Ballarat **Country:** Australia **Facility:** Local Institution - 0023 **State:** Victoria **Zip:** 33500 **Location 24:** **City:** Edegem **Country:** Belgium **Facility:** Local Institution - 0002 **Zip:** 2650 **Location 25:** **City:** Liege **Country:** Belgium **Facility:** Local Institution - 0005 **Zip:** 4000 **Location 26:** **City:** Roeselare **Country:** Belgium **Facility:** Local Institution - 0001 **Zip:** 8800 **Location 27:** **City:** Belo Horizonte **Country:** Brazil **Facility:** Local Institution - 0035 **State:** Minas Gerais **Zip:** 30130-090 **Location 28:** **City:** Ijui **Country:** Brazil **Facility:** Local Institution - 0029 **State:** RIO Grande DO SUL **Zip:** 98700-000 **Location 29:** **City:** São Paulo **Country:** Brazil **Facility:** Local Institution - 0034 **State:** SAO Paulo **Zip:** 05652-900 **Location 30:** **City:** Sao Paulo **Country:** Brazil **Facility:** Local Institution - 0036 **State:** São Paulo **Zip:** 01509-010 **Location 31:** **City:** São Paulo **Country:** Brazil **Facility:** Local Institution - 0106 **Zip:** 01321-001 **Location 32:** **City:** Oshawa **Country:** Canada **Facility:** Local Institution - 0062 **State:** Ontario **Zip:** L1G 2B9 **Location 33:** **City:** Beijing **Country:** China **Facility:** Local Institution - 0115 **State:** Beijing **Zip:** 100021 **Location 34:** **City:** Beijing **Country:** China **Facility:** Local Institution - 0096 **State:** BEI **Zip:** 100142 **Location 35:** **City:** Fuzhou **Country:** China **Facility:** Local Institution - 0137 **State:** Fujian **Zip:** 350001 **Location 36:** **City:** Fuzhou **Country:** China **Facility:** Local Institution - 0136 **State:** Fujian **Zip:** 350014 **Location 37:** **City:** Hubei Sheng **Country:** China **Facility:** Local Institution - 0151 **State:** Hubei **Zip:** 430079 **Location 38:** **City:** Changsha **Country:** China **Facility:** Local Institution - 0092 **State:** Hunan **Zip:** 410000 **Location 39:** **City:** Changsha **Country:** China **Facility:** Local Institution - 0093 **State:** Hunan **Zip:** 410000 **Location 40:** **City:** Changsha **Country:** China **Facility:** Local Institution - 0091 **State:** Hunan **Zip:** 410008 **Location 41:** **City:** Shanghai **Country:** China **Facility:** Local Institution - 0098 **State:** Shanghai **Zip:** 200010 **Location 42:** **City:** Shanghai **Country:** China **Facility:** Local Institution - 0165 **State:** Shanghai **Zip:** 200030 **Location 43:** **City:** Shanghai **Country:** China **Facility:** Local Institution - 0113 **State:** Shanghai **Zip:** 200433 **Location 44:** **City:** Chengdu **Country:** China **Facility:** Local Institution - 0088 **State:** Sichuan **Zip:** 610041 **Location 45:** **City:** Hangzhou **Country:** China **Facility:** Local Institution - 0099 **State:** Zhejiang **Zip:** 310016 **Location 46:** **City:** Shanghai **Country:** China **Facility:** Local Institution - 0095 **Zip:** 200032 **Location 47:** **City:** Praha 2 **Country:** Czechia **Facility:** Local Institution - 0041 **Zip:** 128 08 **Location 48:** **City:** Praha 4 **Country:** Czechia **Facility:** Local Institution - 0042 **Zip:** 140 59 **Location 49:** **City:** Besancon **Country:** France **Facility:** Local Institution - 0073 **Zip:** 25030 **Location 50:** **City:** La Tronche **Country:** France **Facility:** Local Institution - 0037 **Zip:** 38700 **Location 51:** **City:** Montpellier **Country:** France **Facility:** Local Institution - 0050 **Zip:** 34295 **Location 52:** **City:** Paris Cedex 18 **Country:** France **Facility:** Local Institution - 0038 **Zip:** 75018 **Location 53:** **City:** Paris Cedex 20 **Country:** France **Facility:** Local Institution - 0051 **Zip:** 75970 **Location 54:** **City:** Rennes Cedex 9 **Country:** France **Facility:** Local Institution - 0083 **Zip:** 35033 **Location 55:** **City:** Rouen **Country:** France **Facility:** Local Institution - 0146 **Zip:** 76000 **Location 56:** **City:** Köln **Country:** Germany **Facility:** Local Institution - 0110 **State:** Nordrhein-Westfalen **Zip:** 51109 **Location 57:** **City:** Berlin **Country:** Germany **Facility:** Local Institution - 0085 **Zip:** 13353 **Location 58:** **City:** Frankfurt **Country:** Germany **Facility:** Local Institution - 0065 **Zip:** 60488 **Location 59:** **City:** Georgsmarienhuette **Country:** Germany **Facility:** Local Institution - 0072 **Zip:** 49124 **Location 60:** **City:** Hamm **Country:** Germany **Facility:** Local Institution - 0071 **Zip:** 59063 **Location 61:** **City:** Heidelberg **Country:** Germany **Facility:** Local Institution - 0108 **Zip:** 69126 **Location 62:** **City:** Immenstadt **Country:** Germany **Facility:** Local Institution - 0109 **Zip:** 87509 **Location 63:** **City:** Loewenstein **Country:** Germany **Facility:** Local Institution - 0064 **Zip:** 74245 **Location 64:** **City:** Ludwigsburg **Country:** Germany **Facility:** Local Institution - 0147 **Zip:** 71640 **Location 65:** **City:** Luebeck **Country:** Germany **Facility:** Local Institution - 0063 **Zip:** 23538 **Location 66:** **City:** Moers **Country:** Germany **Facility:** Local Institution - 0070 **Zip:** 47441 **Location 67:** **City:** Muenchen **Country:** Germany **Facility:** Local Institution - 0066 **Zip:** 81675 **Location 68:** **City:** Dublin **Country:** Ireland **Facility:** Local Institution - 0016 **Zip:** D24 DH74 **Location 69:** **City:** Forlì **Country:** Italy **Facility:** Local Institution - 0024 **Zip:** 47014 **Location 70:** **City:** Milano **Country:** Italy **Facility:** Local Institution - 0026 **Zip:** 20122 **Location 71:** **City:** Parma **Country:** Italy **Facility:** Azienda Ospedaliera Di Parma **Zip:** 43126 **Location 72:** **City:** Nagoya-shi **Country:** Japan **Facility:** Local Institution - 0135 **State:** Aichi **Zip:** 4640021 **Location 73:** **City:** Kashiwa-shi **Country:** Japan **Facility:** Local Institution - 0124 **State:** Chiba **Zip:** 2778577 **Location 74:** **City:** Kitakyushu-shi **Country:** Japan **Facility:** Local Institution - 0129 **State:** Fukuoka **Zip:** 8078556 **Location 75:** **City:** Kobe-shi **Country:** Japan **Facility:** Local Institution - 0127 **State:** Hyogo **Zip:** 6500047 **Location 76:** **City:** Kanazawa-shi **Country:** Japan **Facility:** Local Institution - 0144 **State:** Ishikawa **Zip:** 9208641 **Location 77:** **City:** Yokohama **Country:** Japan **Facility:** Local Institution - 0125 **State:** Kanagawa **Zip:** 241-8515 **Location 78:** **City:** Sendai-shi **Country:** Japan **Facility:** Local Institution - 0131 **State:** Miyagi **Zip:** 9800873 **Location 79:** **City:** Sakai-shi **Country:** Japan **Facility:** Local Institution - 0126 **State:** Osaka **Zip:** 5918555 **Location 80:** **City:** Kitaadachigun **Country:** Japan **Facility:** Local Institution - 0130 **State:** Saitama **Zip:** 3620806 **Location 81:** **City:** Bunkyo-ku **Country:** Japan **Facility:** Local Institution - 0142 **State:** Tokyo **Zip:** 1138431 **Location 82:** **City:** Bunkyo-ku **Country:** Japan **Facility:** Local Institution - 0133 **State:** Tokyo **Zip:** 1138603 **Location 83:** **City:** Chuo-ku **Country:** Japan **Facility:** Local Institution - 0143 **State:** Tokyo **Zip:** 1040045 **Location 84:** **City:** Chuo-ku **Country:** Japan **Facility:** Local Institution - 0134 **State:** Tokyo **Zip:** 5418567 **Location 85:** **City:** Fukushima-shi **Country:** Japan **Facility:** Local Institution - 0132 **Zip:** 960-1295 **Location 86:** **City:** Hiroshima **Country:** Japan **Facility:** Local Institution - 0128 **Zip:** 734-8551 **Location 87:** **City:** Guadalajara **Country:** Mexico **Facility:** Local Institution - 0077 **State:** Jalisco **Zip:** 44280 **Location 88:** **City:** Monterrey **Country:** Mexico **Facility:** Local Institution - 0027 **State:** Nuevo Leon **Zip:** 64460 **Location 89:** **City:** Chihuahua **Country:** Mexico **Facility:** Local Institution - 0028 **Zip:** 31000 **Location 90:** **City:** Groningen **Country:** Netherlands **Facility:** Local Institution - 0004 **Zip:** 9700RB **Location 91:** **City:** Rotterdam **Country:** Netherlands **Facility:** Local Institution - 0003 **Zip:** 3015 GD **Location 92:** **City:** Kraków **Country:** Poland **Facility:** Local Institution - 0049 **State:** Małopolskie **Zip:** 31-202 **Location 93:** **City:** Hato Rey **Country:** Puerto Rico **Facility:** Local Institution - 0117 **Zip:** 00917 **Location 94:** **City:** Cluj-Napoca **Country:** Romania **Facility:** Local Institution - 0013 **State:** Cluj **Zip:** 400015 **Location 95:** **City:** Bucuresti **Country:** Romania **Facility:** Local Institution - 0011 **Zip:** 022328 **Location 96:** **City:** Floresti **Country:** Romania **Facility:** Local Institution - 0012 **Zip:** 407280 **Location 97:** **City:** Moscow **Country:** Russian Federation **Facility:** Local Institution **Zip:** 115478 **Location 98:** **City:** Saint-Petersburg **Country:** Russian Federation **Facility:** Local Institution **Zip:** 197758 **Location 99:** **City:** St. Petersburg **Country:** Russian Federation **Facility:** Local Institution **Zip:** 194291 **Location 100:** **City:** St. Petersburg **Country:** Russian Federation **Facility:** Local Institution **Zip:** 198255 **Location 101:** **City:** Madrid **Country:** Spain **Facility:** Local Institution - 0046 **Zip:** 28006 **Location 102:** **City:** Majadahonda - Madrid **Country:** Spain **Facility:** Local Institution - 0044 **Zip:** 28222 **Location 103:** **City:** Valencia **Country:** Spain **Facility:** Local Institution - 0045 **Zip:** 46026 **Location 104:** **City:** Kaohsiung City **Country:** Taiwan **Facility:** Local Institution - 0149 **Zip:** 807 **Location 105:** **City:** Kaohsiung **Country:** Taiwan **Facility:** Local Institution - 0119 **Zip:** 833 **Location 106:** **City:** New Taipei City **Country:** Taiwan **Facility:** Local Institution - 0116 **Zip:** 235 **Location 107:** **City:** Taipei City **Country:** Taiwan **Facility:** Local Institution - 0112 **Zip:** 100225 **Location 108:** **City:** Taunton **Country:** United Kingdom **Facility:** Local Institution - 0007 **Zip:** TA1 5DA #### Overall Officials **Official 1:** **Affiliation:** Bristol-Myers Squibb **Name:** Bristol-Myers Squibb **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Leal TA, Ramalingam SS. Neoadjuvant therapy gains FDA approval in non-small cell lung cancer. Cell Rep Med. 2022 Jul 19;3(7):100691. doi: 10.1016/j.xcrm.2022.100691. **PMID:** 35858590 **Citation:** Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022 Apr 1;82(7):1396-1408. doi: 10.1158/0008-5472.CAN-21-1382. **PMID:** 35135810 #### See Also Links **Label:** BMS Clinical Trial Information **URL:** https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html **Label:** BMS Clinical Trial Patient Recruiting **URL:** https://www.bmsstudyconnect.com/content/studyconnect/us/en/clinical-trials/NCT04025879.html ## 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: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M5260 - Name: Bronchial 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: D000000972 - Term: Antineoplastic Agents, Phytogenic - ID: D000000970 - Term: Antineoplastic Agents - ID: D000050257 - Term: Tubulin Modulators - ID: D000050256 - Term: Antimitotic Agents - ID: D000050258 - Term: Mitosis Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000082082 - Term: Immune Checkpoint Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000005493 - Term: Folic Acid Antagonists - ID: D000019384 - Term: Nucleic Acid Synthesis Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Micro - Name: Micronutrients - Abbrev: Hemat - Name: Hematinics - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M19537 - Name: Paclitaxel - Relevance: HIGH - As Found: Surgery - ID: M231 - Name: Albumin-Bound Paclitaxel - Relevance: LOW - As Found: Unknown - ID: M6182 - Name: Cisplatin - Relevance: LOW - As Found: Unknown - ID: M1854 - Name: Nivolumab - Relevance: HIGH - As Found: Prospective - ID: M1668 - Name: Docetaxel - Relevance: HIGH - As Found: Physical - ID: M18650 - Name: Carboplatin - Relevance: HIGH - As Found: System - ID: M264 - Name: Pemetrexed - Relevance: HIGH - As Found: General - ID: M26197 - Name: Tubulin Modulators - Relevance: LOW - As Found: Unknown - ID: M26196 - Name: Antimitotic Agents - Relevance: LOW - As Found: Unknown - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: M8619 - Name: Folic Acid Antagonists - Relevance: LOW - As Found: Unknown - ID: T447 - Name: Folinic Acid - Relevance: LOW - As Found: Unknown - 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: D000017239 - Term: Paclitaxel - ID: D000077143 - Term: Docetaxel - ID: D000016190 - Term: Carboplatin - ID: D000077594 - Term: Nivolumab - ID: D000068437 - Term: Pemetrexed ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02374879 **Brief Title:** User Performance and System Accuracy Evaluations Using Glucose Adjustment **Official Title:** User Performance and System Accuracy Evaluations Using Glucose Adjustment #### Organization Study ID Info **ID:** 3128466 #### Organization **Class:** INDUSTRY **Full Name:** LifeScan ### Status Module #### Completion Date **Date:** 2015-02-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-08-16 **Type:** ACTUAL **Last Update Submit Date:** 2017-08-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-02-01 **Type:** ACTUAL #### Start Date **Date:** 2015-02-01 **Type:** ACTUAL **Status Verified Date:** 2017-08 #### Study First Post Date **Date:** 2015-03-02 **Type:** ESTIMATED **Study First Submit Date:** 2015-02-18 **Study First Submit QC Date:** 2015-02-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** LifeScan #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is an open-label, non-randomised pilot study, to evaluate user performance and system accuracy in blood Glucose monitoring system with glucose adjustment. Twelve male and female volunteers aged 18-45, with a documented diagnosis of Type I diabetes for at least 12 will be enrolled in this study. ### Conditions Module **Conditions:** - Type 1 Diabetes Mellitus ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Intervention: Blood Glucose monitoring System (BGMS) Results obtained from the BGMS for UP and SA are compared to a reference instrument (YSI) **Intervention Names:** - Device: Blood Glucose Monitoring Systems. **Label:** Blood Glucose monitoring System (BGMS) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Blood Glucose monitoring System (BGMS) **Description:** In vitro diagnostic medical device. **Name:** Blood Glucose Monitoring Systems. **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** UP evaluation of blood glucose monitoring systems compared to a reference instrument. Samples collected by subject and HCP **Measure:** User Performance (UP) evaluation. **Time Frame:** Up to 6 hours **Description:** UP evaluation of blood glucose monitoring systems compared to a reference instrument. Samples collected by HCP only. **Measure:** System Accuracy (SA) evaluation **Time Frame:** Up to 6 hours ### Eligibility Module **Eligibility Criteria:** Summary of inclusion criteria. * Male and female volunteers aged 18-45, with a documented diagnosis of Type I diabetes for at least 12 months and treated with a basal bolus insulin regime, and deemed otherwise healthy as determined by medical history, physical examination, laboratory test values, vital signs and 12-lead ECGs at screening. * Non-smokers from at least 12 months before study start and for the duration of the study. * Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2. * Able to voluntarily provide written informed consent to participate in the study. * Must understand the purposes and risks of the study and agree to follow the restrictions and schedule of procedures as defined in the protocol, as confirmed during the informed consent process. * Must be willing to consent to have data entered into The Over Volunteering Prevention System (TOPS). * The volunteer's primary care physician has confirmed within the last 12 months that there is nothing in their medical history that would preclude their enrolment into a clinical study. * User Performance Accuracy Testing Only: Self-Monitoring - Volunteer is currently performing unassisted self-monitoring of blood glucose. Summary of exclusion criteria. * A severe hypoglycaemic reaction, defined as causing loss of consciousness and/or requiring outside assistance with oral or intravenous glucose or a glucagon injection, within 7 days of the study start date. * Female volunteers who are pregnant or lactating. * Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C. * Current or history of drug or alcohol abuse or a positive drugs of abuse or alcohol test at screening or check-in. * Participation in a clinical drug study during the 90 days prior to study start. * Any clinically significant illness within 30 days prior to study start. * Donation of blood or blood products within 30 days prior to study start, or at any time during the study, except as required by this protocol. * Weekly alcohol intake exceeding the equivalent of 14 units per week for females or 21 units per week for males. * Consumption of alcoholic beverages within 48 hours prior to check-in. * Volunteers with a substantial change in eating habits within 30 days prior to study start or volunteers who cannot comply with the standardised meals proposed for use in the study. * Prior experience with the BGMSs used for the study. * Volunteers who are currently working for, have previously worked for, or have an immediate family member working for a company that manufactures or markets blood glucose monitoring products. * Volunteers who have laboratory training or experience (medical technologist, laboratory technician, laboratory assistant etc). * Volunteers who, in the opinion of the Investigator, are unsuitable for participation in the study. **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Belfast **Country:** United Kingdom **Facility:** BioKinetic Europe Ltd **State:** Antrim **Zip:** BT2 7BA #### Overall Officials **Official 1:** **Affiliation:** BioKinetic Europe Ltd **Name:** David J Bell **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003920 - Term: Diabetes Mellitus - 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: LOW - As Found: Unknown - ID: M7117 - Name: Diabetes Mellitus, Type 1 - Relevance: HIGH - As Found: Type 1 Diabetes Mellitus - 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: D000003922 - Term: Diabetes Mellitus, Type 1 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05914779 **Brief Title:** Impact of Early Antibiotics on Non-Traumatic Out of Hospital Cardiac Arrest (OHCA) **Official Title:** Impact of Early Antibiotics on Non-Traumatic Out of Hospital Cardiac Arrest (OHCA) #### Organization Study ID Info **ID:** IRGC-05-SI-18-356 #### Organization **Class:** INDUSTRY **Full Name:** Hamad Medical Corporation ### Status Module #### Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-16 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-03-01 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2023-06-22 **Type:** ACTUAL **Study First Submit Date:** 2023-05-30 **Study First Submit QC Date:** 2023-06-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hamad Medical Corporation #### Responsible Party **Investigator Affiliation:** Hamad Medical Corporation **Investigator Full Name:** Adeel Ajwad Butt **Investigator Title:** Senior Consultant in Infectious Diseases **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Specific Aim : The specific aim is to conduct a randomized prospective clinical trial to determine whether no antibiotics in OHCA patients in the ED with very low likelihood of infection is non-inferior to early antibiotic treatment. Hypothesis a: 28-day all-cause mortality will be non-inferior in OHCA patients with very low likelihood of infection who do not receive antibiotic therapy compared with those who receive early antibiotic therapy Hypothesis b: There will be no difference in subsequent incidence of proven infections in the no antibiotics vs, early antibiotics groups Hypothesis c: There will be no difference in the length of ICU stay and overall hospital stay in the early antibiotics vs. no antibiotics groups **Detailed Description:** As above ### Conditions Module **Conditions:** - Infection, Bacterial - Out-Of-Hospital Cardiac Arrest ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 1000 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Individuals with low risk of infection after OHCA will be randomized to either 1) early antibiotics, or 2) no antibiotics. Experimental arm received antibiotics as per local hospital clinical care pathways and physician choice. **Intervention Names:** - Other: with antibiotics treatment **Label:** Subject with antibiotics treatment **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Individuals with low risk of infection after OHCA will be randomized to either 1) early antibiotics, or 2) no antibiotics. Active comparator arm will receive no antibiotics, **Intervention Names:** - Other: No use of antibiotics **Label:** Subjects with no antibiotics treatment **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Subjects with no antibiotics treatment **Description:** Subjects will be randomized into antibiotics and no antibiotics groups based on inclusion and exclusion criteria **Name:** No use of antibiotics **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Subject with antibiotics treatment **Description:** with antibiotics treatment **Name:** with antibiotics treatment **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Primary outcome measure is 28-day all-cause mortality in persons who receive no antibiotics compared with those who receive early antibiotics in OHCA patients. **Measure:** 28-day all-cause mortality. likelihood of infection whether they receive early antibiotic therapy or not. **Time Frame:** 28-day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ● Adults aged \>18 years, presenting to HGH ED after out-of-hospital cardiac arrest * Patients with low likelihood of infection as per the definitions provided above * Ability to obtain informed consent from the subjects or their next of kin/family member/legal surrogate in case of incapacitation due to sedation, mechanical ventilation, etc. In case the next of kin is not available, an independent physician who is not a part of the investigative team will complete and sign the checklist as per HMC Policy "RES 11026_Appendix 6.5". (see section 4.1.3 for details) A member of the investigative team and a witness will also sign this form before the potential subject is enrolled in the study. Exclusion Criteria: * Patients who have clear evidence of infection, as defined by criteria for the study. * Patients who have received antibiotics within the last 1 week prior to admission. * Patients with malignancy, except those who have been cured or in complete remission. * Females with known pregnancy. * Known immunocompromised states (including HIV/AIDS, transplant recipients on immunosuppressant drugs, long-term \[\> 3 weeks of prednisone \>5mg/day equivalent\] steroid therapy). * Patients on immunologic disease modifying agents (commonly known as "biologics") * Patients considered "brain-dead" or "vegetative state" * Patients transferred from another hospital, long term care facility or institution * Neutropenia (total WBC \<1,500/mm3 or absolute neutrophil count of \<1,000/mm3) **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Adeel A Butt, MBBS, MS **Phone:** +97433311228 **Role:** CONTACT #### Locations **Location 1:** **City:** Doha **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Aftab M Umar, MD - **Phone:** +97444479364 - **Role:** CONTACT **Country:** Qatar **Facility:** Hamad Medical Corporation **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Hamad Medical Corporation **Name:** Adeel A Butt, MBBS, MS **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - 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: BC14 - Name: Heart and Blood 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: M9411 - Name: Heart Arrest - Relevance: HIGH - As Found: Cardiac Arrest - ID: M29208 - Name: Out-of-Hospital Cardiac Arrest - Relevance: HIGH - As Found: Out-of-hospital Cardiac Arrest - ID: M4722 - Name: Bacterial Infections - Relevance: HIGH - As Found: Infection, Bacterial - ID: M9419 - Name: Heart Diseases - 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 ### Condition Browse Module - Meshes - ID: D000001424 - Term: Bacterial Infections - ID: D000006323 - Term: Heart Arrest - ID: D000058687 - Term: Out-of-Hospital Cardiac Arrest ### Intervention Browse Module - Ancestors - ID: D000000890 - Term: Anti-Infective Agents - ID: D000000995 - Term: Antitubercular 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: M4222 - Name: Anti-Bacterial Agents - Relevance: HIGH - As Found: Initial - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: HIGH - As Found: Initial - ID: M4311 - Name: Antitubercular Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000904 - Term: Antibiotics, Antitubercular ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04705779 **Brief Title:** The HARMONY Study: A Intervention to Reduce Cardiometabolic Risk in African American Women **Official Title:** The HARMONY Study: A Culturally-relevant, Randomized-controlled, Stress Management Intervention to Reduce Cardiometabolic Risk in African American Women #### Organization Study ID Info **ID:** 20-2193 #### Organization **Class:** OTHER **Full Name:** University of North Carolina, Chapel Hill #### Secondary ID Infos **ID:** 1R01MD015388-01A1 **Link:** https://reporter.nih.gov/quickSearch/1R01MD015388-01A1 **Type:** NIH ### Status Module #### Completion Date **Date:** 2025-02-18 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-07 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-06 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2025-02-18 **Type:** ESTIMATED #### Start Date **Date:** 2021-05-20 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2021-01-12 **Type:** ACTUAL **Study First Submit Date:** 2021-01-08 **Study First Submit QC Date:** 2021-01-08 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute on Minority Health and Health Disparities (NIMHD) #### Lead Sponsor **Class:** OTHER **Name:** University of North Carolina, Chapel Hill #### 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 test whether a culturally-tailored nutrition and exercise intervention designed for African-American women will lead to sustained improvements in exercise and healthy eating through improvements in self-management mediators: mindfulness, stress management, positive reappraisal, self-regulation, and self-efficacy. **Detailed Description:** Among all groups of women in the US, African American women (AAW) have the highest rates of death and disability from chronic cardiometabolic (CM) illnesses. Furthermore, AAW have inadequate engagement in exercise and are least successful at achieving and sustaining CM risk-reduction goals compared to all men and women of other racial/ethnic groups, despite participating in comprehensive lifestyle interventions. These alarming disparities are due in part to disproportionately high rates of psychological stress. A shortcoming of interventions with AAW is an inadequate focus on stress exposure, including gender and racialized stress, stress physiology, and stress-related barriers to healthy eating and exercise to reduce CM risk. In response, the HARMONY study is a randomized controlled trial to test a culturally-tailored nutrition and exercise intervention to manage stress, designed to help AAW build on their strengths to promote self-management and to reduce stress-related CM risk. Certain information about the interventions is not disclosed to protect the scientific integrity of the trial. ### Conditions Module **Conditions:** - Heart Diseases - Stroke - Pre-diabetes - Hypertension - Obesity - Overweight - Stress **Keywords:** - HARMONY ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 174 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Following screening, participation includes 8 regular sessions occurring over 4 months followed by 6 monthly booster sessions. Overall, study participation will last approximately 14 months. **Intervention Names:** - Behavioral: HARMONY **Label:** HARMONY **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Following screening, participation includes 8 regular sessions occurring over 4 months followed by 6 monthly booster sessions. Overall, study participation will last approximately 14 months. **Intervention Names:** - Behavioral: Nutrition and Exercise Education (NEEW) **Label:** Nutrition and Exercise Education Workgroup (NEEW) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - HARMONY **Description:** The HARMONY intervention will be delivered over 8 every-other-week sessions and 6 monthly booster sessions. Each session will have three components; an exercise sampler, cool down and tailored education on cardiometabolic prevention and risk reductions. **Name:** HARMONY **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Nutrition and Exercise Education Workgroup (NEEW) **Description:** The Nutrition and Exercise Workgroup (NEEW) group will be delivered over 8 every-other-week sessions and 6 monthly booster sessions. Each session will have three components; an exercise sampler, cool down and tailored education on cardiometabolic prevention and risk reductions. **Name:** Nutrition and Exercise Education (NEEW) **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** The participant's moderate to vigorous physical activity will be measured by triaxial accelerometry. Results will be reported in minutes, with higher numbers indicating a higher amount of moderate to vigorous physical activity. **Measure:** Change in Amount of Moderate to Vigorous Physical Activity **Time Frame:** Baseline, 48 weeks after first group session **Description:** The participant's dietary intake will be assessed using the dietary risk assessment, which includes 54 items. The dietary risk assessment measures the healthiness of a participant's eating habits. Score ranges from 0 to 108, with higher scores associated with less healthy dietary intake. **Measure:** Change in the Dietary Risk Assessment Score **Time Frame:** Baseline, 48 weeks after first group session **Description:** The participant's nutrition will be assessed using the veggie meter, which uses light reflectance spectroscopy to provide an estimated skin carotenoid composite score. Score ranges from 0 to 800, with higher scores associated with greater fruit and vegetable intake. **Measure:** Change in Veggie Meter Score **Time Frame:** Baseline, 48 weeks after first group session #### Secondary Outcomes **Description:** The participant's BMI is calculated as weight (kg) divided by height (cm). **Measure:** Change in BMI **Time Frame:** Baseline, 48 weeks after first group session **Description:** The participants weight will be measured using a digital scale. **Measure:** Change in Weight **Time Frame:** Baseline, 48 weeks after first group session **Description:** The participant's waist to hip ratio is calculated by using the mean of two waist circumference measurements divided by mean of two hip circumference measurements. Waist circumference will be measured at the midpoint between the upper iliac crest and lower costal margin in the midaxillary line. Hip circumference will be measured at the maximum width of the buttocks or gluteo-femoral fold. **Measure:** Change in Waist-to-Hip Ratio **Time Frame:** Baseline, 48 weeks after first group session **Description:** The participant's percent body fat is measured using lange skinfold calipers. The final measurement will be the mean of three measurements on the right side of the body. **Measure:** Change in Percent Body Fat **Time Frame:** Baseline, 48 weeks after first group session **Description:** The participant's blood pressure is measured using an electronic sphygmomanometer. The final measurement will be the mean of three measurements. **Measure:** Change in Blood Pressure (Systolic Blood Pressure/Diastolic Blood Pressure) **Time Frame:** Baseline, 48 weeks after first group session **Description:** The participant's high sensitivity C-reactive protein levels will be obtained via phlebotomy. C-Reactive Protein is an inflammatory biomarker, and indicative of cardiovascular risk. **Measure:** Change in High Sensitivity C-Reactive Protein Amount **Time Frame:** Baseline, 48 weeks after first group session **Description:** The participant's IL-6 levels will be obtained via phlebotomy. IL-6 is an inflammatory biomarker, and indicative of cardiovascular risk. **Measure:** Change in IL-6 **Time Frame:** Baseline, 48 weeks after first group session **Description:** Participant's glycosylated hemoglobin levels will be obtained via phlebotomy. Glycosylated hemoglobin amount is indicative of cardiovascular risk. **Measure:** Change in Glycosylated Hemoglobin **Time Frame:** Baseline, 48 weeks after first group session ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Self-reported African American or Black woman * BMI= 25-39 kg/m\^2 (confirmed at baseline assessment) * At least one cardiometabolic risk factor: * \< 150 minutes of self-reported moderate to vigorous exercise * History of gestational diabetes * Parent or sibling with prediabetes or diabetes * Personal or family history of hypertension (=130/80) * Prediabetes or impaired glucose metabolism (HgbA1c 5.7-6.5) * Personal or family history of abnormal cholesterol levels * At least 18 years of age * Able to read/speak English * Willing to attend scheduled classes, complete internet surveys and biomarker assessments * Able/willing to engage in moderate to vigorous exercise * Ambulatory * Superwoman Schema Questionnaire score indicating at least moderate endorsement of one or more subscales (strength: 7; motional suppression: 7; resistance of vulnerability: 8; motivation to succeed: 7; or helping others: 10) or a total score of 20 or greater * A Perceived Stress Scale-14 score of \>5 or self-report at least "some" general stress. Exclusion Criteria: * Pregnant/anticipated pregnancy * Substance use, mental health or medical condition that will prevent the ability to participate in the intervention * Use of weight loss medication * Current or recent (\<6 months prior to enrollment) engagement in another weight loss or meditation program * Impaired cognition (inability to follow and respond appropriately during screening). * Diabetes diagnosis * Has a confirmed BMI lower than 25 or higher than 39 * Does not have access to a smartphone or computer with internet access * Lives in the same household as someone who is currently in the study or was previously in the study. **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Chapel Hill **Country:** United States **Facility:** The University of North Carolina at Chapel Hill **State:** North Carolina **Zip:** 27599 #### Overall Officials **Official 1:** **Affiliation:** The University of North Carolina at Chapel Hill, School of Nursing **Name:** Cheryl Giscombe, PhD, RN, PMHNP-BC, FAAN **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** All researchers who desire to access the individual participant data must enter into a data-sharing agreement. **Description:** Deidentified individual data that supports the results will be shared up to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC. **IPD Sharing:** YES **Time Frame:** The data will become available per NIH policy, which is no later than the acceptance for publication of the main findings from the dataset. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000044343 - Term: Overnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000001835 - Term: Body Weight - ID: D000003920 - Term: Diabetes Mellitus - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine 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: BC14 - Name: Heart and Blood Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M22306 - Name: Stroke - Relevance: LOW - As Found: Unknown - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M26186 - Name: Overweight - Relevance: HIGH - As Found: Overweight - ID: M14117 - Name: Prediabetic State - Relevance: HIGH - As Found: Pre-diabetes - ID: M9419 - Name: Heart Diseases - Relevance: HIGH - As Found: Heart Disease - ID: M20295 - Name: Glucose Intolerance - Relevance: LOW - As Found: Unknown - ID: M25307 - Name: Overnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - 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 ### Condition Browse Module - Meshes - ID: D000006331 - Term: Heart Diseases - ID: D000050177 - Term: Overweight - ID: D000011236 - Term: Prediabetic State ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03962179 **Acronym:** VACStent **Brief Title:** Feasibility and Efficacy of a Combination of a SEMS and Vacuum Wound Treatment (VACStent) **Official Title:** VAC Stent: A Prospective Feasibility Study for the Treatment of Gastrointestinal Leakage Through a Combination of Covered Nitinol Stent and Negative Pressure Wound Treatment #### Organization Study ID Info **ID:** 19-1053_1 #### Organization **Class:** OTHER **Full Name:** University Hospital of Cologne ### Status Module #### Completion Date **Date:** 2021-11-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2021-08-05 **Type:** ACTUAL **Last Update Submit Date:** 2021-07-29 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2020-11-30 **Type:** ACTUAL #### Start Date **Date:** 2019-09-22 **Type:** ACTUAL **Status Verified Date:** 2021-07 #### Study First Post Date **Date:** 2019-05-23 **Type:** ACTUAL **Study First Submit Date:** 2019-05-21 **Study First Submit QC Date:** 2019-05-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital of Cologne #### Responsible Party **Investigator Affiliation:** University Hospital of Cologne **Investigator Full Name:** Seung-Hun Chon **Investigator Title:** PI **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Open, prospective, one-arm feasibility and efficacy study of a European conformity (CE) certified Combination product of two CE certified medical devices in the intended indication. Evaluation of the suitability of the medical device for sealing leaks in the gastrointestinal tract **Detailed Description:** The investigators analyzed the outcome of using a hybrid medical device (self-expanding metal stents (SEMS) with negative pressure wound therapy) in the treatment of leaks of the upper gastrointestinal tract ### Conditions Module **Conditions:** - Perforation Esophagus - Esophageal Cancer - Esophageal Achalasia - Esophageal Diseases **Keywords:** - Perforation Esophagus, Esophageal Anastomotic Leak, ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patient s who received a VACStent **Intervention Names:** - Device: VACStent **Label:** VACStent Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - VACStent Group **Description:** Evaluation of the suitability of the medical device for sealing leaks in the gastrointestinal tract **Name:** VACStent **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** % of patients with successful implantation of VACStent **Measure:** Technique - % of patients with successful implantation of VACStent **Time Frame:** From date of first implantation of VACStent until the leak is sealed or the treatment is canceled from any serious medical cause, whichever came first, up to 12 months #### Secondary Outcomes **Description:** % of patients with a sealed leak after successful treatment with VACStent **Measure:** Healing of leak - % of patients with successful implantation of VACStent **Time Frame:** From date of first implantation of VACStent until the leak is sealed or the treatment is canceled from any serious medical cause, whichever came first, up to 12 months **Description:** % of patients with successful treatment of sepsis leak after successful implantation of VACStent **Measure:** Treatment of sepsis **Time Frame:** From date of first implantation of VACStent until the leak is sealed or the treatment is canceled from any serious medical cause, whichever came first, up to 12 months **Description:** % of patients with migration of VACStent after successful implantation of VACStent **Measure:** Migration rate **Time Frame:** From date of first implantation of VACStent until the leak is sealed or the treatment is canceled from any serious medical cause, whichever came first, up to 12 months **Description:** % of patients with bleeding after successful implantation of VACStent **Measure:** Bleeding **Time Frame:** From date of first implantation of VACStent until the leak is sealed or the treatment is canceled from any serious medical cause, whichever came first, up to 12 months **Description:** % of patients with % of patients with bleeding after successful implantation of VACStent after successful treatment with VACStent **Measure:** Arrosion of tissue structures **Time Frame:** From date of first implantation of VACStent until the leak is sealed or the treatment is canceled from any serious medical cause, whichever came first, up to 12 months **Description:** % of patients with a sealed leak after successful treatment with VACStent **Measure:** Sealing of leak - % of patients with successful implantation of VACStent **Time Frame:** From date of first implantation of VACStent until the leak is sealed or the treatment is canceled from any serious medical cause, whichever came first, up to 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with spontaneous, iatrogenic or postoperative leakage in the esophagus, evidence of leakage through an endoscopic examination * Accessibility of the leak with the delivery system of the VAC stent Exclusion Criteria: * Simultaneous participation in other interventional exams * Endoscopic inaccessibility of the affected section * Full anticoagulation with international normalized ratio (INR) \> 1.5 and / or partial thromboplastin time (PTT) \> 50 sec, or platelets \<20.000 / μl (after therapeutic correction an inclusion is possible) * Unstable patients with severe septic disease, who have a clinical history * Assessment an immediate operation for safe focus switch-off requires * Ileus image with constant vomiting (after nasogastric tube and gastric emptying an inclusion possible) * Persons who are in a dependency / employment relationship with the sponsor or examiner stand * Accommodation in an institution for judicial or regulatory purposes arrangement **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Cologne **Country:** Germany **Facility:** University Hospital of Cologne **State:** NRW **Zip:** 50937 #### Overall Officials **Official 1:** **Affiliation:** University Hospital of Cologne **Name:** Seung-Hun Chon, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Chon SH, Bartella I, Burger M, Rieck I, Goeser T, Schroder W, Bruns CJ. VACStent: a new option for endoscopic vacuum therapy in patients with esophageal anastomotic leaks after upper gastrointestinal surgery. Endoscopy. 2020 May;52(5):E166-E167. doi: 10.1055/a-1047-0244. Epub 2019 Dec 2. No abstract available. **PMID:** 31791095 **Citation:** Chon SH, Scherdel J, Rieck I, Lorenz F, Dratsch T, Kleinert R, Gebauer F, Fuchs HF, Goeser T, Bruns CJ. A new hybrid stent using endoscopic vacuum therapy in treating esophageal leaks: a prospective single-center experience of its safety and feasibility with mid-term follow-up. Dis Esophagus. 2022 Apr 19;35(4):doab067. doi: 10.1093/dote/doab067. **PMID:** 34561712 #### See Also Links **Label:** A Novel Hybrid Stent with Endoscopic Vacuum Therapy for Treating Leaks of the Upper Gastrointestinal Tract **URL:** https://www.karger.com/Article/Abstract/512320 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004066 - Term: Digestive System Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000015154 - Term: Esophageal Motility Disorders - ID: D000003680 - Term: Deglutition Disorders - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M8088 - Name: Esophageal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8081 - Name: Esophageal Achalasia - Relevance: HIGH - As Found: Esophageal Achalasia - ID: M8085 - Name: Esophageal Diseases - Relevance: HIGH - As Found: Esophageal Diseases - ID: M28891 - Name: Anastomotic Leak - Relevance: LOW - As Found: Unknown - ID: M8089 - Name: Esophageal Perforation - Relevance: HIGH - As Found: Perforation Esophagus - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M17874 - Name: Esophageal Motility Disorders - Relevance: LOW - As Found: Unknown - ID: M17875 - Name: Esophageal Spasm, Diffuse - Relevance: LOW - As Found: Unknown - ID: M6882 - Name: Deglutition Disorders - Relevance: LOW - As Found: Unknown - ID: T2141 - Name: Esophageal Cancer - Relevance: HIGH - As Found: Esophageal Cancer - ID: T2993 - Name: Idiopathic Achalasia - Relevance: HIGH - As Found: Esophageal Achalasia - ID: T970 - Name: Cardiospasm - Relevance: HIGH - As Found: Esophageal Achalasia ### Condition Browse Module - Meshes - ID: D000004931 - Term: Esophageal Achalasia - ID: D000004935 - Term: Esophageal Diseases - ID: D000004939 - Term: Esophageal Perforation ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04877379 **Brief Title:** VNRX-7145 Drug-Drug Interaction in Healthy Adult Volunteers **Official Title:** VNRX-7145-102: A Randomized, Drug-Drug Interaction Study to Assess the Safety and Pharmacokinetics (PK) of VNRX-7145 and VNRX-5024 (Ceftibuten) in Healthy Adult Volunteers #### Organization Study ID Info **ID:** VNRX-7145-102 #### Organization **Class:** INDUSTRY **Full Name:** Venatorx Pharmaceuticals, Inc. #### Secondary ID Infos **ID:** 272201600029C-P00007-9999-2 **Link:** https://reporter.nih.gov/quickSearch/272201600029C-P00007-9999-2 **Type:** NIH ### Status Module #### Completion Date **Date:** 2021-11-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-06-15 **Type:** ACTUAL **Last Update Submit Date:** 2022-06-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-11-10 **Type:** ACTUAL #### Start Date **Date:** 2021-06-08 **Type:** ACTUAL **Status Verified Date:** 2022-06 #### Study First Post Date **Date:** 2021-05-07 **Type:** ACTUAL **Study First Submit Date:** 2021-05-03 **Study First Submit QC Date:** 2021-05-03 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Allergy and Infectious Diseases (NIAID) #### Lead Sponsor **Class:** INDUSTRY **Name:** Venatorx Pharmaceuticals, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study will provide an initial assessment of the safety and PK of VNRX-7145 and VNRX-5024 (ceftibuten) when administered as single agents and with co-administration in a single dose cross-over design in Part 1. In Part 2, subjects will receive 500 mg of VNRX-7145 or matching placebo q8h for 10 days. VNRX-7145 and VNRX-5024 (ceftibuten) will be administered every 8 hours (q8h) for 10 days at 2 dose levels of VNRX-7145 in Part 3. ### Conditions Module **Conditions:** - Healthy Subjects ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SEQUENTIAL **Intervention Model Description:** Part 1: Crossover Parts 2\&3: Parallel ##### Masking Info **Masking:** DOUBLE **Masking Description:** Part 1: Unblinded Parts 2\&3: Blinded **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 53 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will receive single doses of VNRX-7145 or VNRX-5024 alone and in combination. All subjects will receive study drug in the sequence specified by the randomization schedule. **Intervention Names:** - Drug: VNRX-7145 - Drug: VNRX-5024 (ceftibuten) **Label:** Part 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Multiple dose administration of VNRX-7145 q8h for 10 days **Intervention Names:** - Drug: VNRX-7145 **Label:** Part 2A **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Multiple dose administration of placebo q8h for 10 days **Intervention Names:** - Drug: Placebo **Label:** Part 2B **Type:** PLACEBO_COMPARATOR #### Arm Group 4 **Description:** Multiple dose administration of low dose VNRX-7145 + VNRX-5024 **Intervention Names:** - Drug: VNRX-7145 - Drug: VNRX-5024 (ceftibuten) **Label:** Part 3A **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Multiple dose administration of high dose VNRX-7145 + VNRX-5024 **Intervention Names:** - Drug: VNRX-7145 - Drug: VNRX-5024 (ceftibuten) **Label:** Part 3B **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** Multiple dose administration of Placebo (matching VNRX-7145 + VNRX-5024) **Intervention Names:** - Drug: Placebo **Label:** Part 3C **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Part 1 - Part 2A - Part 3A - Part 3B **Description:** β-lactamase inhibitor **Name:** VNRX-7145 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Part 1 - Part 3A - Part 3B **Description:** β-lactam antibiotic **Name:** VNRX-5024 (ceftibuten) **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Part 2B - Part 3C **Description:** Placebo **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** concentration time data **Measure:** Part 1: Cmax **Time Frame:** 0-48 hours **Description:** Area under the concentration-time curve from time-zero extrapolated to infinity based on collected PK **Measure:** Part 1: AUC0-inf **Time Frame:** 0-48 hours **Measure:** Parts 2&3: Number of subjects with adverse events **Time Frame:** Day 15 (+2) #### Secondary Outcomes **Measure:** Part 1: Number of subjects with adverse events **Time Frame:** Day 14 (+2) **Measure:** Parts 2&3: AUC0-tau **Time Frame:** Day 1 **Measure:** Parts 2&3: AUC0-tau **Time Frame:** Day 10 **Measure:** Parts 2&3: Cmax **Time Frame:** Day 1 **Measure:** Parts 2&3: Cmax **Time Frame:** Day 10 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Healthy adults 18-55 years 2. Males or non-pregnant, non-lactating females 3. Body mass index (BMI): ≥18.5 kg/m2 and ≤32.0 kg/m2 4. Normal blood pressure 5. Normal lab tests Exclusion Criteria: 1. History or presence of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, autoimmune, hematologic, neoplastic, or neurological disorders 2. History of drug allergy or hypersensitivity to penicillin, cephalosporin, or beta-lactam antibacterial drug 3. Use of antacid medications 4. Abnormal ECG or history of clinically significant abnormal rhythm disorder 5. Positive alcohol, drug, or tobacco use/test **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Groningen **Country:** Netherlands **Facility:** PRA Health Sciences - Early Development Services ## Derived Section ### Intervention Browse Module - Ancestors - 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: 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: M30450 - Name: beta-Lactamase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M1883 - Name: Ceftibuten - Relevance: HIGH - As Found: Follitropin Delta - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077722 - Term: Ceftibuten ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05627479 **Acronym:** MAGIK **Brief Title:** MAGIK for Femoral/Tibial Shaft Fractures **Official Title:** Muscle Trauma, ATP Depletion, and Glucose-Insulin-Potassium Therapy (The MAGIK Trial): A Randomized, Controlled Feasibility Study of GIK Therapy to Decrease Skeletal Muscle Injury in Trauma Patients With Femoral Shaft (OTA 32A-C) and Tibial Shaft (OTA 42A-C) Fractures #### Organization Study ID Info **ID:** 22-01118 #### Organization **Class:** OTHER **Full Name:** NYU Langone Health ### Status Module #### Completion Date **Date:** 2027-01-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-28 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-01-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-12-01 **Type:** ESTIMATED **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2022-11-25 **Type:** ACTUAL **Study First Submit Date:** 2022-11-17 **Study First Submit QC Date:** 2022-11-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** NYU Langone Health #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this phase 2 randomized control trial will be to evaluate the effect of glucose-insulin-potassium (GIK) therapy in the setting of lower extremity trauma to reduce short- and long-term muscle damage, acute rhabdomyolysis, and acute kidney injury. The study will consist of 40 patients with femur or tibial shaft fractures randomized to the GIK arm (using a well-described systemic GIK protocol; n = 20) or the control arm (using isotonic saline; n = 20). The use of systemic GIK is expected to decrease the overall amount of lower extremity muscle cell death and result in improved muscle function in the postoperative period. Additionally, the investigators hypothesize that GIK will lead to less severe rhabdomyolysis and a concomitant decrease in the incidence of AKI that results from the byproducts of muscle cell death. ### Conditions Module **Conditions:** - Femoral Shaft Fracture - Tibial Shaft Fracture ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In patients randomized to the GIK Therapy Arm, a stepwise GIK infusion process will be performed. Baseline lab values that are markers of skeletal muscle injury (CPK), acute kidney injury (creatinine), and general tissue perfusion (lactate) will be obtained within the first 30 min of arrival to the ED. Subsequently, serial CPK, creatinine, myoglobin and lactate values will be obtained at regularly scheduled intervals until a minimum of 72 hours after definitive fixation or until rhabdomyolysis is resolved and/or kidney function has normalized **Intervention Names:** - Drug: GIK solution **Label:** GIK Therapy **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients randomized to the control cohort will receive a normal saline infusion instead of GIK. Standard institutional ICU protocol will be used to monitor potassium and glucose levels per current standard-of-care practices and abnormal lab values will be treated accordingly per standard institutional protocols. **Intervention Names:** - Drug: Isotonic Normal Saline Solution **Label:** Placebo Control **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - GIK Therapy **Description:** Therapy cocktail of Glucose, Insulin and Potassium. The medications will be prepared as per standard protocol. Administered intravenously. **Name:** GIK solution **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo Control **Description:** Placebo injection - administered intravenously. **Name:** Isotonic Normal Saline Solution **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Measured via standard of care lab assessment. **Measure:** Peak Creatine Kinase (CK) Concentration During Hospital Stay **Time Frame:** Up to Day 7 Post-Operation #### Secondary Outcomes **Measure:** Number of Participants who Experience Acute Kidney Injury (AKI) **Time Frame:** Up to Week 52 Post-Operation **Measure:** Number of Participants with Stage 1 AKI **Time Frame:** Up to Week 52 Post-Operation **Measure:** Number of Participants with Stage 2 AKI **Time Frame:** Up to Week 52 Post-Operation **Measure:** Number of Participants with Stage 3 AKI **Time Frame:** Up to Week 52 Post-Operation **Description:** Measure of self-reported capability rather than actual performance of physical activities. The raw score is the sum of responses and is calculated into a T-score with a mean of 50 and a standard deviation of 10; higher scores indicate greater physical function. **Measure:** Patient Reported Outcome Measurement Information System (PROMIS) Physical Function **Time Frame:** Up to Week 52 Post-Operation **Description:** Measured via handheld dynamometer. **Measure:** Quadriceps Muscle Strength in the Uninjured Leg **Time Frame:** Up to Week 52 **Description:** Measured via handheld dynamometer. **Measure:** Quadriceps Muscle Strength in the Injured Leg **Time Frame:** Up to Week 52 **Description:** Measured via handheld dynamometer. **Measure:** Hamstrings Muscle Strength in the Uninjured Leg **Time Frame:** Up to Week 52 **Description:** Measured via handheld dynamometer. **Measure:** Hamstrings Muscle Strength in the Injured Leg **Time Frame:** Up to Week 52 **Description:** Muscle volume calculated via MRI. **Measure:** Uninjured Femur Muscle Volume at Week 4 Post-Op **Time Frame:** Week 4 Post-Operation **Description:** Muscle volume calculated via MRI. **Measure:** Injured Femur Muscle Volume at Week 4 Post-Op **Time Frame:** Week 4 Post-Operation **Description:** Muscle volume calculated via MRI. **Measure:** Uninjured Femur Muscle Volume at Week 24 Post-Op **Time Frame:** Week 24 Post-Operation **Description:** Muscle volume calculated via MRI. **Measure:** Injured Femur Muscle Volume at Week 24 Post-Op **Time Frame:** Week 24 Post-Operation **Description:** Muscle volume calculated via MRI. **Measure:** Uninjured Femur Muscle Volume at Week 52 Post-Op **Time Frame:** Week 52 Post-Operation **Description:** Muscle volume calculated via MRI. **Measure:** Injured Femur Muscle Volume at Week 52 Post-Op **Time Frame:** Week 52 Post-Operation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Femoral shaft fracture or tibial shaft fracture 2. Survival \> 72 hours after definitive femur fracture fixation Exclusion Criteria: 1. Pregnant women as the safety of GIK therapy in pregnant women has not been studied. 2. Age below 18 years 3. Survival \< 72 hours after definitive femur fixation. 4. Pathologic fracture 5. Low energy bisphosphonate related atypical fracture 6. Patients with a contraindication to any of the medications on the study list 7. Patients with prior extremity weakness resulting from stroke or other neurological condition 8. Patients with absolute contraindications to undergoing MRI (implanted defibrillator or pacemaker, implanted deep brain stimulator, bullets or gunshot pellets near great vessels or vital organs, cerebral aneurysm clips, cochlear implants, magnetic dental implants). **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Matthew Kingery, MD **Phone:** 212-598-6000 **Role:** CONTACT #### Locations **Location 1:** **City:** New York **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Matthew Kingery, MD - **Phone:** 212-598-6000 - **Role:** CONTACT **Country:** United States **Facility:** NYU Langone Health **State:** New York **Zip:** 10016 #### Overall Officials **Official 1:** **Affiliation:** NYU Langone Health **Name:** Sanjit Konda, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** The investigator who proposed to use the data will be given access to the data upon reasonable request. Requests should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement. **Description:** The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: \[[email protected]\]. 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 **IPD Sharing:** YES **Time Frame:** Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research. ## 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: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M26370 - Name: Fractures, Bone - Relevance: HIGH - As Found: Fracture ### Condition Browse Module - Meshes - ID: D000050723 - Term: Fractures, Bone ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: HIGH - As Found: Procedure - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000019999 - Term: Pharmaceutical Solutions ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06199479 **Brief Title:** Radiologic Pathologic Correlation of Imaging to Distinguish True Progression From Pseudoprogression in Brain Malignancies **Official Title:** Radiologic Pathologic Correlation of Imaging to Distinguish True Progression From Pseudoprogression in Brain Malignancies #### Organization Study ID Info **ID:** 2023-0671 #### Organization **Class:** OTHER **Full Name:** M.D. Anderson Cancer Center #### Secondary ID Infos **Domain:** NCI-CTRP Clinical Registry **ID:** NCI-2023-11127 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2025-10-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-10 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-29 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-10-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-30 **Type:** ESTIMATED **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2024-01-10 **Type:** ACTUAL **Study First Submit Date:** 2023-12-29 **Study First Submit QC Date:** 2023-12-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** M.D. Anderson Cancer Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** To learn if advanced imaging methods can tell apart true progression (the disease has actually gotten worse) from pseudoprogression (the disease appears to have gotten worse, but it actually has not). **Detailed Description:** Primary Objectives To determine if advanced imaging findings can correlate with tissue changes in order to distinguish true progression from pseudoprogression. We will recruit participants with new suspicious enhancement developing during treatment for glioma, and systematically perform: a) high quality routine MR imaging (including routine, diffusion, permeability, perfusion and spectroscopy imaging as part of our regular ABTI protocol) and compare this imaging to b) pathology obtained by means of stereotactic biopsy. Pathology will serve as the gold standard to determine which imaging strategies are most successful in distinguishing between true Tumor recurrence and Pseudoprogression for each lesion. Secondary Objectives 1. To assess the feasibility of Contrast Clearance MR (delayed T1 enhanced MR) subtraction maps in distinguishing Pseudoprogression from true progression. 2. To gather observational data for Dual Energy CT imaging and delayed contrast clearance with Dual Energy CT in the assessment of glioma. 3. To correlate quantitative imaging biomarkers (derived from MR imaging data) along the biopsy tract with histological and clinical biomarkers. This exploratory data could generate novel comparisons to determine those imaging biomarkers that are most effective at predicting (a) cellular density and, (b) the types and relative numbers of cells present in the brain. 4. To observe clinical outcomes such as progression free survival and overall survival in the trial population and relate these to imaging findings. ### Conditions Module **Conditions:** - Brain Malignancies - Pseudoprogression ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The tests and procedures done as part of your standard-of-care biopsy preparation, participants will also have advanced MRI and CT scans performed no later than 2 weeks before the biopsy. Typically, these scans are done within 1 or 2 days before surgery to provide the most accurate images to the surgeon. **Intervention Names:** - Procedure: MRI Scan - Procedure: CT Scan - Procedure: Biopsy **Label:** Arm 1 **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm 1 **Description:** Performed by MRI Scan **Name:** MRI Scan **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Arm 1 **Description:** Performed by CT Scan **Name:** CT Scan **Type:** PROCEDURE #### Intervention 3 **Arm Group Labels:** - Arm 1 **Description:** Standard of Care Biopsy **Name:** Biopsy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) **Measure:** Safety and adverse events (AEs) **Time Frame:** Through study completion; an average of 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Participants is \>18 years old. The pediatric population has a different disease profile from adult glioma participants. To reduce heterogeneity in the patient population we will not consider participants younger than 18 for this study. 2. The participants agrees to participate in the clinical study and to complete all required visits and evaluations. 3. Participants has undergone prior treatment for a brain tumor and has a new suspicious imaging finding requiring diagnostic workup and is being considered for biopsy. 4. Participants agrees to undergo, prior to the procedure, the needed imaging evaluation (within 14 days and preferably with 3 days of the planned procedure). Exclusion Criteria: 1. Renal failure as evidenced by a GFR of less than 30 mL/min/1.73m2 for gadolinium based imaging. In the absence of eGFR lab result, participants is not excluded in the absence of remarkable pathological renal history, as confirmed by and in the discretion of the PI. 2. For iodinated contrast agent we will use the more strict cut-off of 45 mL/min/1.73m2 ((Davenport, Perazella et al. 2020), Consensus statement from the ACR and the National Kidney Foundation). The different threshold reflects the different risk profiles of these agents. Participants with GFR in the range 30-45 can receive a Non-Contrast DECT (CT contrast withheld). 3. Pacemakers, electronic stimulation, metallic foreign bodies and devices and/or other conditions that are not MR safe, which include but are not limited to: * electronically, magnetically, and mechanically activated implants * ferromagnetic or electronically operated active devices like automatic cardioverter defibrillators and cardiac pacemakers * metallic splinters in the eye * ferromagnetic hemostatic clips in the central nervous system (CNS) or body * cochlear implants * other pacemakers, e.g., for the carotid sinus * insulin pumps and nerve stimulators * non-MR safe lead wires * prosthetic heart valves (if dehiscence is suspected) * non-ferromagnetic stapedial implants * pregnancy * claustrophobia that does not readily respond to oral medication. 4. Allergy to relevant imaging contrast agents, includes allergies to iodine or gadolinium-based contrast agents (if one class of agents is contra-indicated, then imaging with the other can still proceed). **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Dawid Schellingerhout, MD **Phone:** (713) 794-5673 **Role:** CONTACT #### Locations **Location 1:** **City:** Houston **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dawid Schellingerhout, MD - **Phone:** 713-794-5673 - **Role:** CONTACT ***Contact 2:*** - **Name:** Dawid Schellingerhout, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** MD Anderson Cancer Center **State:** Texas **Zip:** 77030 #### Overall Officials **Official 1:** **Affiliation:** M.D. Anderson Cancer Center **Name:** Dawid Schellingerhout, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### See Also Links **Label:** MD Anderson Cancer Center **URL:** http://www.mdanderson.org ## 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: M20559 - Name: Disease Progression - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009369 - Term: Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03365479 **Brief Title:** Acute Response of Iloprost Inhalation Using the Breelib Nebulizer in Pulmonary Arterial Hypertension **Official Title:** Acute Hemodynamic Response of Iloprost Inhalation Using the Breelib Nebulizer in Pulmonary Arterial Hypertension #### Organization Study ID Info **ID:** V04_21112017 #### Organization **Class:** OTHER **Full Name:** University of Giessen ### Status Module #### Completion Date **Date:** 2018-10-24 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-10-26 **Type:** ACTUAL **Last Update Submit Date:** 2018-10-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-08-01 **Type:** ACTUAL #### Start Date **Date:** 2017-05-01 **Type:** ACTUAL **Status Verified Date:** 2018-10 #### Study First Post Date **Date:** 2017-12-07 **Type:** ACTUAL **Study First Submit Date:** 2017-11-27 **Study First Submit QC Date:** 2017-12-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Giessen #### Responsible Party **Investigator Affiliation:** University of Giessen **Investigator Full Name:** Jan Grimminger **Investigator Title:** Study Chair: Ghofrani H. Ardeschir, Prof. Dr. University of Giessen **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:** Primary objective • To evaluate the effect of rapid inhalation of 2.5μgiloprost using the Breelib nebulizer on pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension Secondary objectives * To evaluate the effect of rapid iloprost inhalation using the Breelib nebulizer on mean pulmonary arterial pressure (mPAP), cardiac output (CO), cardiac index (CI), systemic blood pressure, arterial oxygen saturation, heart rate, and pulmonary arterial wedge pressure (PAWP). * To evaluate the safety and tolerability of the rapid iloprost inhalation using the Breelib nebulizer. **Detailed Description:** This study aims to investigate the acute hemodynamic and pharmacological effects of a single inhalation of Iloprost (2.5μg) during right heart catheterization (RHC) using the Breelib nebulizer. Patients with confirmed diagnosis of pulmonary arterial hypertension (PAH = WHO group 1), NYHA functional class III and with stable background pulmonary vasoactive treatment or treatment naïve PAH patients will be challenged with the iloprost inhalation dosage during RHC. As a proof-of concept design, the study will include consecutive PAH patients only challenged with a single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer during right heart catheterization (day 2). The acute hemodynamic response will be followed over 30 minutes. Change of pulmonary hemodynamics, systemic blood pressure, right ventricular echocardiographic parameters and adverse events will be assessed at baseline and 5, 10, 15, 30 minutes after the end of inhalation. Recently, the Breelib nebulizer has been evaluated within a multicenter, randomized, unblinded, study. This safety and feasibility study compared inhalation time, pharmacokinetics, and acute tolerability of inhaled iloprost delivered via Breelib versus the standard I-Neb nebulizer. The primary safety endpoints (AEs) were reported with a low frequency and were consistent with the known safety profile of iloprost. Median inhalation times were considerably shorter while maximum iloprost plasma concentration and systemic exposure were significantly higher, with Breelib versus I-Neb. Previously, it was shown that the acute hemodynamic response of iloprost inhalation via the previous used I-Neb nebulizer resulted in a relevant and significant reduction of PVR and increase in CI. Moreover, previous generation of nebulizers also resulted in a significant reduction of PVR and increase in CI 5-15min after iloprost inhalation. Therefore, the aim of the current study is to determine the acute hemodynamic effects on the pulmonary and the systemic circulation as well as on the gas exchange of 2.5 μg iloprost delivered via the Breelib device. The investigators aim to characterize the hemodynamic profile of the inhalation with Breelib as the investigators speculate that the shortened inhalation time will result in an enhanced hemodynamic response with substantial reduction of pulmonary vascular resistance (PVR). Moreover, as a secondary outcome measurement the investigators aim to assess the response of mean pulmonary arterial pressure, cardiac index/cardiac output, systemic blood pressure, right ventricular echocardiographic parameters and oxygen saturation after inhalation of 2.5μg iloprost and analyze adverse events. ### Conditions Module **Conditions:** - Pulmonary Hypertension - Pulmonary Arterial Hypertension **Keywords:** - pulmonary hypertension - iloprost - inhaled - breelib - nebulizer - pulmonary arterial hypertension ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The study comprises a 1-day Screening period, followed by a right heart catheterization with a single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer **Intervention Names:** - Drug: Iloprost **Label:** Study cohort **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Study cohort **Description:** Single administration of inhaled iloprost 2.5 μg delivered via Breelib nebulizer **Name:** Iloprost **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Change of PVR (∆PVR) **Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation #### Secondary Outcomes **Measure:** Change of mPAP **Time Frame:** at baseline and 5, 10, 15, 30 minutes after the end of inhalation **Measure:** Change of PAWP **Time Frame:** at baseline and 5, 10, 15, 30 minutes after the end of inhalation **Measure:** Change of CI **Time Frame:** at baseline and 5, 10, 15, 30 minutes after the end of inhalation **Measure:** Change of systemic blood pressure **Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation **Measure:** Change of oxygen saturation **Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation **Measure:** Change of right heart echocardiography **Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation **Measure:** Adverse events (AEs) **Time Frame:** 5, 10, 15, 30 minutes after the end of inhalation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Confirmed diagnosis of pulmonary arterial hypertension, WHO group 1 diagnosed according to current guidelines * New York Heart Association functional class III * mPAP ≥ 25 mmHg, PAWP ≤ 15 mmHg * Age ≥ 18 years; ≤ 85 years * planned right heart catheterization based on clinical grounds * Stable specific PAH medications other than prostanoids * Signed informed consent Exclusion Criteria: * other etiologic groups of pulmonary hypertension (WHO group 2, 3, 4, 5) * Unstable or severe coronary artery disease (history of cardiac surgery, history of coronary intervention 2 years prior to inclusion), uncontrolled arterial hypertension, severe left ventricular hypertrophy, severe congenital or acquired valvular or myocardial disease, systolic blood pressure \< 90 mmHg, heart rate of \<55 or \>105 beats·min-1 before inhalation * Progressive left heart failure History of severe ventricular arrhythmias * Pulmonary veno-occlusive disease * Transitory ischemic attack (TIA) or stroke ≤ 3months * Severe hepatic impairment (\> CHILD B) * Severe, terminal renal impairment * Use of intravenous, subcutaneous or oral prostacyclin/IP receptor agonists * Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of results **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Giessen **Country:** Germany **Facility:** University Clinic Giessen and Marburg **State:** Hesse **Zip:** 35392 **Location 2:** **City:** Bad Nauheim **Country:** Germany **Facility:** Kerckhoff-Klinik ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - 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: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M27137 - Name: Respiratory Aspiration - Relevance: LOW - As Found: Unknown - ID: M10027 - Name: Hypertension, Pulmonary - Relevance: HIGH - As Found: Pulmonary Hypertension - ID: M2261 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension - ID: M30541 - Name: Familial Primary Pulmonary Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension - 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 - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T4807 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension ### Condition Browse Module - Meshes - ID: D000006976 - Term: Hypertension, Pulmonary - ID: D000081029 - Term: Pulmonary Arterial Hypertension - ID: D000065627 - Term: Familial Primary Pulmonary Hypertension - ID: D000006973 - Term: Hypertension ### Intervention Browse Module - Ancestors - ID: D000010975 - Term: Platelet Aggregation Inhibitors - ID: D000014665 - Term: Vasodilator Agents ### 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: M18735 - Name: Iloprost - Relevance: HIGH - As Found: Cyst - ID: M13865 - Name: Platelet Aggregation Inhibitors - Relevance: LOW - As Found: Unknown - ID: M17412 - Name: Vasodilator Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000016285 - Term: Iloprost ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04605679 **Brief Title:** Hepatitis C Virus (HCV) Positive Kidney Grafts in HCV Negative Recipients **Official Title:** Transplantation of HCV Donor Kidneys in HCV Negative or Previously Successfully Treated Recipients #### Organization Study ID Info **ID:** 5200098 #### Organization **Class:** OTHER **Full Name:** Loma Linda University ### Status Module #### Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-05 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-03 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Start Date **Date:** 2020-05-06 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2020-10-28 **Type:** ACTUAL **Study First Submit Date:** 2020-10-25 **Study First Submit QC Date:** 2020-10-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Loma Linda University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** To determine the efficacy and safety of transplanting HCV positive kidney allografts to HCV sero-negative patients who are on the waiting list. ### Conditions Module **Conditions:** - Kidney Failure **Keywords:** - HCV ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 31 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** A single center, open-label, pilot study examining 20 adult HCV negative kidney transplant patients who receive an HCV infected graft. Target start date for antiviral therapy will be within 3 months after kidney transplantation, unless extenuating clinical circumstances arise (such as the development of fibrosing cholestatic HCV, which would prompt earlier treatment, or clinical events or comorbidities which would prompt delay in treatment). **Intervention Names:** - Procedure: Kidney Transplantation **Label:** Recipient of HCV positive kidney graft **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Recipient of HCV positive kidney graft **Description:** A HCV negative or previously successfully treated recipient with a HCV positive kidney graft **Name:** Kidney Transplantation **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Will track subjects post transplant for 12 months **Measure:** 1-year graft and patient survival **Time Frame:** From the date of transplant through the last day of 12 month post transplant ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female * Age 18 and older * English and Spanish speaking patients * Active on the waiting list for kidney transplantation * Donor organ with Antibody and NAT (nucleic acid test) positive for HCV * HCV negative recipient; this includes patients who never had HCV and those with HCV previously eradicated with antiviral therapy. The latter is defined as those with undetectable HCV viral load at least 3 months since stopping therapy. * Willing and able to provide written informed consent Exclusion Criteria: * Participants co-infected with HIV * Donor previously treated with an NS5a containing regimen (if treatment history of donor known) * Known allergies or hypersensitivity to DAA or RBV * Pregnancy and/or actively breastfeeding **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Loma Linda **Country:** United States **Facility:** Loma Linda University Health-Transplant Institute **State:** California **Zip:** 92354 #### Overall Officials **Official 1:** **Affiliation:** Loma Linda University Health **Name:** Michael E de Vera, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Reese PP, Abt PL, Blumberg EA, Van Deerlin VM, Bloom RD, Potluri VS, Levine M, Porrett P, Sawinski D, Nazarian SM, Naji A, Hasz R, Suplee L, Trofe-Clark J, Sicilia A, McCauley M, Gentile C, Smith J, Niknam BA, Bleicher M, Reddy KR, Goldberg DS. Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients: A Single-Group Trial. Ann Intern Med. 2018 Sep 4;169(5):273-281. doi: 10.7326/M18-0749. Epub 2018 Aug 7. **PMID:** 30083748 **Citation:** Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, Wesson R, Reyad A, Naqvi FF, Ostrander D, Sugarman J, Segev DL, Sulkowski M, Desai NM. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med. 2018 Apr 17;168(8):533-540. doi: 10.7326/M17-2871. Epub 2018 Mar 6. **PMID:** 29507971 #### See Also Links **Label:** Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients **URL:** https://pubmed.ncbi.nlm.nih.gov/30083748 **Label:** Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients **URL:** https://pubmed.ncbi.nlm.nih.gov/29507971 ## 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: BC01 - Name: Infections - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M9592 - Name: Hepatitis A - Relevance: LOW - As Found: Unknown - ID: M9591 - Name: Hepatitis - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M9611 - Name: Hepatitis C - Relevance: LOW - As Found: Unknown - 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 ### Condition Browse Module - Meshes - ID: D000051437 - Term: Renal Insufficiency ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04358679 **Brief Title:** Upper Limb Ergometer on Pulmonary Function Among Patients With Spinal Cord Injury. **Official Title:** Effects of Upper Limb Ergometer on Pulmonary Function Among Patients With Spinal Cord Injury. #### Organization Study ID Info **ID:** REC/00592 Somia Ilyas #### Organization **Class:** OTHER **Full Name:** Riphah International University ### Status Module #### Completion Date **Date:** 2020-01-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-04-24 **Type:** ACTUAL **Last Update Submit Date:** 2020-04-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-12-30 **Type:** ACTUAL #### Start Date **Date:** 2019-09-01 **Type:** ACTUAL **Status Verified Date:** 2020-04 #### Study First Post Date **Date:** 2020-04-24 **Type:** ACTUAL **Study First Submit Date:** 2020-04-20 **Study First Submit QC Date:** 2020-04-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Riphah International University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Randomized Control Trial, To determine the effects of arm ergometer exercise on pulmonary function of Spinal Cord Injury. **Detailed Description:** The spinal cord is a tubular structure contained nervous tissue. This acts as a transmission channel of nerve signals within the brain and spinal cord. It contains grey and white matter. The grey matter consists of cell bodies of different sensory and motor neurons and white matter consists of oriented spinal tracts. By 2007, a prospective observational study had been conducted after a disaster occurred in Pakistan which was the most cataclysmic natural disaster in country's history as a result 73000 people were lost their lives and 126000 were harmed. There was no Spinal Cord Injury (SCI) registry existed in the country but according to different estimates 650-750 had been effected of SCI. In United States SCI incidence mainly due to higher percentage of violence-related SCIs (18%)which is higher compared to the western Europe (8%) Australia (2%). In Pakistan the most common traumatic cause of SCI was falling from different cause followed by road traffic accident (RAT) (25.2%) and functional aerobic impairment (FAI) (8.4%). The way that SCI is associated with fantastic expenses and human sufferings , yet careful statistics of SCI are not accessible in dominant of developing countries including Pakistan. Total lung capacities become abnormal in chronic spinal cord injury patients. Changes in chest wall compliance and decreased respiratory muscle strength leads to abnormal changes in overall lung capacities. ### Conditions Module **Conditions:** - Spinal Cord Injuries **Keywords:** - Pulmonary Function - Spinal Cord Injury - Spirometry - Ergometer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 44 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Conventional Treatment: Deep breathing, Assisted coughing, Sustained stretching, Splinting, Bracing and Functional mobility **Intervention Names:** - Other: Conventional Treatment **Label:** Conventional Treatment **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Conventional Treatment + Upper Limb (UL) ergo-meter exercise **Intervention Names:** - Other: Upper Limb ergometer training **Label:** Upper Limb ergometer training **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Conventional Treatment **Description:** Conventional Treatment: * Deep breathing: 10-15 reps, twice a day (BD) * Assisted coughing 10-15 reps, BD * range of motion (ROM)+ stretching 10 reps, BD * Tilt table standing **Name:** Conventional Treatment **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Upper Limb ergometer training **Description:** Conventional Treatment + upper limb (UL) ergometry exercise UL ergometry exercise 15 to 20 mints , 2 times ,five days per week for 6 weeks. **Name:** Upper Limb ergometer training **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Changes from the Baseline, the digital spirometer is used in clinical setting to analyze Forced vital Capacity in Liters **Measure:** Forced vital Capacity (FVC) **Time Frame:** 6 Week **Description:** Changes from the Baseline, the digital spirometer is used in clinical setting to analyze Forced Expiratory Volume in 1 second FEV1 in Liters **Measure:** Forced Expiratory Volume in 1 second (FEV1) **Time Frame:** 6 Week **Description:** Changes from the Baseline, the digital spirometer is used in clinical setting to analyze peak expiratory flow PEF in Liter/second. **Measure:** Peak Expiratory Flow (PEF) **Time Frame:** 6 Week ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * SCI at level of upper and lower thoracic spine Exclusion Criteria: * Cardiovascular diseases * Active inflammation or infection going in body * Malignancies * Those Individuals with have psychiatric disorders * Any other neurological condition related to brain (stroke, parkinson's etc) * Pressure ulcers (grade 3 and grade 4) **Maximum Age:** 45 Years **Minimum Age:** 25 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Peshawar **Country:** Pakistan **Facility:** Paraplegic Center Peshawar **State:** Khyber Pakhtunkhwa **Zip:** 25000 #### Overall Officials **Official 1:** **Affiliation:** Riphah International University **Name:** Iqbal Tariq, MsCPPT **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Maynard FM Jr, Bracken MB, Creasey G, Ditunno JF Jr, Donovan WH, Ducker TB, Garber SL, Marino RJ, Stover SL, Tator CH, Waters RL, Wilberger JE, Young W. International Standards for Neurological and Functional Classification of Spinal Cord Injury. American Spinal Injury Association. Spinal Cord. 1997 May;35(5):266-74. doi: 10.1038/sj.sc.3100432. No abstract available. **PMID:** 9160449 **Citation:** Kirshblum SC, Burns SP, Biering-Sorensen F, Donovan W, Graves DE, Jha A, Johansen M, Jones L, Krassioukov A, Mulcahey MJ, Schmidt-Read M, Waring W. International standards for neurological classification of spinal cord injury (revised 2011). J Spinal Cord Med. 2011 Nov;34(6):535-46. doi: 10.1179/204577211X13207446293695. No abstract available. **PMID:** 22330108 **Citation:** Terson de Paleville D, Lorenz D. Compensatory muscle activation during forced respiratory tasks in individuals with chronic spinal cord injury. Respir Physiol Neurobiol. 2015 Oct;217:54-62. doi: 10.1016/j.resp.2015.07.001. Epub 2015 Jul 11. **PMID:** 26169572 **Citation:** Arsh A, Darain H, Haq ZU, Zeb A, Ali I, Ilyas SM. Epidemiology of spinal cord injuries due to bomb blast attacks, managed at paraplegic centre peshawar, pakistan: a nine years retrospective study. KMUJ: KHYBER MEDICAL UNIVERSITY JOURNAL. 2017;9(2). **Citation:** Postma K, Bussmann JB, Haisma JA, van der Woude LH, Bergen MP, Stam HJ. Predicting respiratory infection one year after inpatient rehabilitation with pulmonary function measured at discharge in persons with spinal cord injury. J Rehabil Med. 2009 Sep;41(9):729-33. doi: 10.2340/16501977-0410. **PMID:** 19774306 **Citation:** Devillard X, Rimaud D, Roche F, Calmels P. Effects of training programs for spinal cord injury. Ann Readapt Med Phys. 2007 Jul;50(6):490-8, 480-9. doi: 10.1016/j.annrmp.2007.04.013. Epub 2007 Apr 24. English, French. **PMID:** 17482709 **Citation:** Kloosterman MG, Snoek GJ, Jannink MJ. Systematic review of the effects of exercise therapy on the upper extremity of patients with spinal-cord injury. Spinal Cord. 2009 Mar;47(3):196-203. doi: 10.1038/sc.2008.113. Epub 2008 Sep 30. **PMID:** 18825160 **Citation:** Postma K, Haisma JA, de Groot S, Hopman MT, Bergen MP, Stam HJ, Bussmann JB. Changes in pulmonary function during the early years after inpatient rehabilitation in persons with spinal cord injury: a prospective cohort study. Arch Phys Med Rehabil. 2013 Aug;94(8):1540-6. doi: 10.1016/j.apmr.2013.02.006. Epub 2013 Feb 14. **PMID:** 23416767 **Citation:** Torhaug T, Brurok B, Hoff J, Helgerud J, Leivseth G. Arm Cycling Combined with Passive Leg Cycling Enhances VO2peak in Persons with Spinal Cord Injury Above the Sixth Thoracic Vertebra. Top Spinal Cord Inj Rehabil. 2018 Winter;24(1):86-95. doi: 10.1310/sci17-00029. Epub 2017 Nov 20. **PMID:** 29434464 **Citation:** DeVeau KM, Harman KA, Squair JW, Krassioukov AV, Magnuson DSK, West CR. A comparison of passive hindlimb cycling and active upper-limb exercise provides new insights into systolic dysfunction after spinal cord injury. Am J Physiol Heart Circ Physiol. 2017 Nov 1;313(5):H861-H870. doi: 10.1152/ajpheart.00046.2017. Epub 2017 Jul 14. **PMID:** 28710067 **Citation:** West CR, Currie KD, Gee C, Krassioukov AV, Borisoff J. Active-Arm Passive-Leg Exercise Improves Cardiovascular Function in Spinal Cord Injury. Am J Phys Med Rehabil. 2015 Nov;94(11):e102-6. doi: 10.1097/PHM.0000000000000358. **PMID:** 26259052 **Citation:** Zhan S, Cerny FJ, Gibbons WJ, Mador MJ, Wu YW. Development of an unsupported arm exercise test in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil. 2006 May-Jun;26(3):180-7; discussion 188-90. doi: 10.1097/00008483-200605000-00013. **PMID:** 16738459 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013118 - Term: Spinal Cord Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000020196 - Term: Trauma, Nervous System ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M15916 - Name: Spinal Cord Injuries - Relevance: HIGH - As Found: Spinal Cord Injury - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Injury - ID: M15915 - Name: Spinal Cord Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013119 - Term: Spinal Cord Injuries - ID: D000014947 - Term: Wounds and Injuries ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04842279 **Brief Title:** FACE-Q in Facial Reconstructive Surgery: A Prospective Database **Official Title:** FACE-Q Measurement of the Patient Perspective in Facial Reconstructive Surgery: A Prospective Database #### Organization Study ID Info **ID:** 9446 #### Organization **Class:** OTHER **Full Name:** McMaster University ### Status Module #### Completion Date **Date:** 2022-04-20 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-04-13 **Type:** ACTUAL **Last Update Submit Date:** 2021-04-08 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-07-20 **Type:** ESTIMATED #### Start Date **Date:** 2021-04-20 **Type:** ESTIMATED **Status Verified Date:** 2021-04 #### Study First Post Date **Date:** 2021-04-13 **Type:** ACTUAL **Study First Submit Date:** 2021-04-08 **Study First Submit QC Date:** 2021-04-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** McMaster University #### Responsible Party **Investigator Affiliation:** McMaster University **Investigator Full Name:** Mark McRae **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:** The primary objective is to establish a prospective database of clinical information, FACE-Q scores, and patient photographs (as appropriate) to enhance the understanding and practice of facial plastic and reconstructive surgery. **Detailed Description:** Patient perspective is essential as medicine progresses to become more patient centered. FACE-Q is a recently developed and validated patient-reported outcome measure (PROM) tool that allows clinicians to assess patient perspectives after skin cancer surgery of the face. The FACE-Q has more than 40 independent scales and checklist each measuring different patient reported outcomes (PRO). The FACE-Q utilizes five scales to measure the psychometric, QoL, patient experience, and cosmetic outcomes. The FACE-Q was validated in both surgical and non-surgical patients. This is a single-center project to establish a prospective database of clinical information from patients who utilize FACE-Q in a clinical investigation. This database is being established in efforts to promote research in various patient populations Rationale The purpose of this prospective database would be to evaluate levels of satisfaction and QoL across various interventions and patient populations after using the FACE-Q PROM. Long term data collection will include information related to QoL, patient experience, and cosmetic outcomes. Many areas related to patient reported outcomes in the context of facial reconstruction surgery are in their early years. There are many areas of research needed to aid in clinical decision making. The database will allow these questions to be answered using a retrospective model and will provide the background information required to mount larger scale randomized controlled trials, when possible. Information collected in the database will also allow meaningful research to be conducted in a timely and cost-effective manner. For example database information could help answer, "Which patient characteristics are associated with higher FACE-Q scores in non-melanoma facial cancer patients?". The investigators will initiate a line of investigations that will characterize adults who use the FACE-Q in various clinical contexts with the ultimate goal of improving patient outcomes. The study was designed in concordance with the Enhancing the Quality and Transparency of Health Research (EQUATOR) reporting guidelines using: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statements as well as based off previous prospective studies that used FACE-Q for PROMs. ### Conditions Module **Conditions:** - Skin Cancer, Basal Cell Skin Cancer Skin Cancer, Non-Melanoma Skin Cancers - Squamous Cell Carcinoma Patient Satisfaction ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 300 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** FACE-Q is a recently developed and validated patient reported outcome measure (PROM) tool that allows clinicians to assess patient perspectives after skin cancer surgery of the face.The PROM is used to assess the perspective and impact of skin cancer as well as its treatment on the patient's quality of life (QoL). Patients with skin cancer may have increased anxiety, social isolation, and cosmetic concerns after surgery. The FACE-Q utilizes five scales to measure the psychometric, QoL, patient experience, and cosmetic outcomes. Raw scores are transformed to a 0-100 scale with a higher score indicating a better outcome. Any studies using FACE-Q for facial surgery reconstruction at our center may be eligible for inclusion in the database **Name:** FACE-Q scale **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** FACE-Q is a recently developed and validated patient reported outcome measure (PROM) tool that allows clinicians to assess patient perspectives after skin cancer surgery of the face.The PROM is used to assess the perspective and impact of skin cancer as well as its treatment on the patient's quality of life (QoL). Patients with skin cancer may have increased anxiety, social isolation, and cosmetic concerns after surgery. The FACE-Q utilizes five scales to measure the psychometric, QoL, patient experience, and cosmetic outcomes. Raw scores are transformed to a 0-100 scale with a higher score indicating a better outcome **Measure:** FACE-Q score **Time Frame:** 12 months #### Secondary Outcomes **Description:** Patient photos may be taken post-op from the other studies and will be included if performed **Measure:** Facial photos **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: i. Age 18 years or older ii. Use of any module of the FACE-Q scale to measure a patient-reported outcome iii. Ability to provide informed consent Exclusion Criteria: i. Those patients who do not meet all of the above inclusion criteria will be excluded from the study **Healthy Volunteers:** True **Maximum Age:** 100 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** This database will collect existing or prospective data that is part of standard clinical care from the electronic medical record of patients which are part of any FACE-Q studies. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mark McRae, MD **Phone:** 905) 522-1155 **Phone Ext:** 32145 **Role:** CONTACT #### Locations **Location 1:** **City:** Hamilton **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mark MccRa, MD - **Phone:** (905) 522-1155 - **Phone Ext:** 32145 - **Role:** CONTACT ***Contact 2:*** - **Name:** Mark McRae, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Matthew McRae, MD - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Sophocles Voineskos, MD - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Minh Huynh, MD - **Role:** SUB_INVESTIGATOR **Country:** Canada **Facility:** St. Joseph's Healthcare Hamilton **State:** Ontario **Status:** RECRUITING **Zip:** L8N 4A6 #### Overall Officials **Official 1:** **Affiliation:** McMaster University **Name:** Mark McRae, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: M5537 - Name: Carcinoma, Basal Cell - Relevance: HIGH - As Found: Basal Cell Skin Cancer - ID: M15681 - Name: Skin Neoplasms - Relevance: HIGH - As Found: Skin Cancer - ID: M21089 - Name: Facies - Relevance: LOW - As Found: Unknown - ID: M20439 - Name: Neoplasms, Basal Cell - Relevance: HIGH - As Found: Cancer, Basal Cell - 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: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012878 - Term: Skin Neoplasms - ID: D000002280 - Term: Carcinoma, Basal Cell - ID: D000018295 - Term: Neoplasms, Basal Cell ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04003779 **Brief Title:** Reconfiguring the Patient Room to Increase Patient Stability **Official Title:** Reconfiguring the Patient Room for a Fall Protection Strategy to Increase Patient Stability During Ambulation #### Organization Study ID Info **ID:** 00099410 #### Organization **Class:** OTHER **Full Name:** University of Utah ### Status Module #### Completion Date **Date:** 2024-09-29 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-08 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-07 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09 **Type:** ESTIMATED #### Start Date **Date:** 2022-07-14 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2019-07-01 **Type:** ACTUAL **Study First Submit Date:** 2019-06-25 **Study First Submit QC Date:** 2019-06-28 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** The Center for Health Design #### Lead Sponsor **Class:** OTHER **Name:** University of Utah #### Responsible Party **Investigator Affiliation:** University of Utah **Investigator Full Name:** Bob Wong **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:** Despite decades of research into patient falls, falls and the injuries incurred continue to be a serious threat to patient safety. Fall rates continue to be unacceptably high. The purpose of this project is to increase the safety of a hospital room for patient mobility, using innovative simulation strategies and patient-centric design. **Detailed Description:** Despite decades of research into patient falls, falls and the injuries incurred continue to be a serious threat to patient safety. Fall rates continue to be unacceptably high. The purpose of this project is to increase the safety of a hospital room for patient mobility, using innovative simulation strategies and patient-centric design. An innovative simulation environment will be built to enable rapid assessment of room layout and fixture positioning and patient stability. The results from multiple simulations will be used to fabricate a prototype room layout that will be tested by patients with Parkinson disease and reviewed and updated with input from other relevant stakeholders. A final room prototype will be built and tested. Results will be translated and shared with all stakeholders and disseminated for implementation. ### Conditions Module **Conditions:** - Elderly, Frail - Accidental Falls - Hospitals ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Using virtual reality and ergonomic measures, we will sequentially adjust features of the hospital room to determine the most stable gate in frail elderly patients. ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Single-arm. Ergonomically exploring patient stability moving around various configurations of a hospital room. **Intervention Names:** - Other: Room configuration **Label:** Participant stability with various room configurations **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Participant stability with various room configurations **Description:** Adjust distance, handrails, degrees of turn for participant **Name:** Room configuration **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Increased balance **Measure:** Gait: increased stability **Time Frame:** 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Frail elderly, impaired gait Exclusion Criteria: * Use of walking aid **Minimum Age:** 60 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Bob G Wong, PhD **Phone:** 801-587-9666 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Andrew Merryweather, PhD **Role:** CONTACT #### Locations **Location 1:** **City:** Salt Lake City **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Bo Foreman - **Phone:** 801-581-3496 - **Role:** CONTACT **Country:** United States **Facility:** Dumke Health Professions Building **State:** Utah **Status:** RECRUITING **Zip:** 84108 #### Overall Officials **Official 1:** **Affiliation:** University of Utah **Name:** Bob G Wong, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of Utah **Name:** Andrew Merryweather, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01564979 **Brief Title:** Effect on Tear Functions of Pretarsal and Preseptal Techniques of Botulinum Toxin Type A Injection in Hemifacial Spasm **Official Title:** Effect on Tear Functions of Pretarsal and Preseptal Techniques of Botulinum Toxin Type A Injection in Hemifacial Spasm #### Organization Study ID Info **ID:** KTS-001-BTX #### Organization **Class:** OTHER **Full Name:** Khon Kaen University ### Status Module #### Completion Date **Date:** 2012-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2012-03-28 **Type:** ESTIMATED **Last Update Submit Date:** 2012-03-27 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2012-09 **Type:** ESTIMATED #### Start Date **Date:** 2012-04 **Status Verified Date:** 2012-03 #### Study First Post Date **Date:** 2012-03-28 **Type:** ESTIMATED **Study First Submit Date:** 2012-03-18 **Study First Submit QC Date:** 2012-03-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Khon Kaen University #### Responsible Party **Investigator Affiliation:** Khon Kaen University **Investigator Full Name:** kitthisak kitthaweesin **Investigator Title:** Assoc Prof **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to determine whether pretarsal and preseptal techniques of Botulinum toxin type A injection have any effect on tear functions. **Detailed Description:** Botulinum toxin type A has been used for hemifacial spasm since 1986. of Botulinum toxin type A can be subcutaneously injected at pretarsal or preseptal portion of orbicularis muscle. Blepharoptosis has been reported less frequently with pretarsal technique, however dry eye was noticed in one patient treated with pretarsal botulinum toxin type A for cosmetic purpose. ### Conditions Module **Conditions:** - Hemifacial Spasm **Keywords:** - botulinum toxin - facial nerve - hemifacial spasm - tears ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 26 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: preseptal injection of botulinum toxin type A **Label:** preseptal **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: pretarsal injection of Botulinum toxin type A **Label:** pretarsal **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - preseptal **Description:** botulinum toxin type A (Botox)2.5 units, 5 points **Name:** preseptal injection of botulinum toxin type A **Other Names:** - Botox **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - pretarsal **Description:** Botulinum toxin type A 2,5 units, 5 points **Name:** pretarsal injection of Botulinum toxin type A **Other Names:** - Botox **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** unit of measure; minutes **Measure:** tear break up time **Time Frame:** change from baseline in tear break up time at 12 weeks #### Secondary Outcomes **Description:** units of measurement; millimeters **Measure:** schirmer's test **Time Frame:** change from baseline of schirmer's test at 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * patient diagnosed with hemifacial spasm Exclusion Criteria: * previous history of botulinum toxin treatment for hemifacial spasm * ocular surface disorders * tear disorders * evidence of infection at or around eyelids * pregnant woman * other neurologic disease, i.e. OMG * coagulopathy or treatment with thrombolytic agent * treatment with aminoglycosides, chloroquine, hydroxychloroquine **Maximum Age:** 70 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** kitthisak kitthaweesin, ND **Phone:** 6643348383 **Role:** CONTACT #### Locations **Location 1:** **City:** Muang **Contacts:** ***Contact 1:*** - **Name:** kitthisak kitthaweesin, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 2:*** - **Name:** Pawat Phusetwong, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Thailand **Facility:** Khon Kaen University **State:** Khon Kaen **Zip:** 40002 #### Overall Officials **Official 1:** **Affiliation:** Khon Kaen University **Name:** kitthisak kithaweesin, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Price J, O'Day J. A comparative study of tear secretion in blepharospasm and hemifacial spasm patients treated with botulinum toxin. J Clin Neuroophthalmol. 1993 Mar;13(1):67-71. **PMID:** 8501266 ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2015-05-31 - Date Unknown: Unknown #### Event: RESET - Date: 2015-06-15 - Date Unknown: Unknown ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020879 - Term: Neuromuscular Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000009135 - Term: Muscular Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC07 - Name: Mouth and Tooth Diseases ### Condition Browse Module - Browse Leaves - ID: M15241 - Name: Rupture - Relevance: LOW - As Found: Unknown - ID: M15837 - Name: Spasm - Relevance: HIGH - As Found: Spasm - ID: M21089 - Name: Facies - Relevance: LOW - As Found: Unknown - ID: M22785 - Name: Lacerations - Relevance: LOW - As Found: Unknown - ID: M12077 - Name: Muscle Cramp - Relevance: HIGH - As Found: Spasm - ID: M21505 - Name: Hemifacial Spasm - Relevance: HIGH - As Found: Hemifacial Spasm - ID: M22619 - Name: Neuromuscular Manifestations - Relevance: LOW - As Found: Unknown - 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: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009120 - Term: Muscle Cramp - ID: D000019569 - Term: Hemifacial Spasm - ID: D000013035 - Term: Spasm ### 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: M5183 - Name: Botulinum Toxins - Relevance: HIGH - As Found: Face - ID: M21257 - Name: Botulinum Toxins, Type A - Relevance: HIGH - As Found: Weight loss - ID: M250193 - Name: abobotulinumtoxinA - Relevance: HIGH - As Found: Weight loss - 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: D000001905 - Term: Botulinum Toxins - ID: D000019274 - Term: Botulinum Toxins, Type A - ID: C000542869 - Term: abobotulinumtoxinA ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2015-05-31 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2015-05-31 - Reset Date: 2015-06-15 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02237079 **Acronym:** BIM **Brief Title:** Bazedoxifene/Conjugated Estrogens (BZA/CE) Improvement of Metabolism (BIM) **Official Title:** Bazedoxifene/Conjugated Estrogens (BZA/CE) Improvement of Metabolism (BIM) #### Organization Study ID Info **ID:** WI190523 #### Organization **Class:** OTHER **Full Name:** Tulane University ### Status Module #### Completion Date **Date:** 2018-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-26 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-04 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-06-26 **Type:** ACTUAL **Results First Submit Date:** 2023-02-28 **Results First Submit QC Date:** 2023-05-30 #### Start Date **Date:** 2014-12 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2014-09-11 **Type:** ESTIMATED **Study First Submit Date:** 2014-08-26 **Study First Submit QC Date:** 2014-09-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Tulane University Health Sciences Center #### Responsible Party **Investigator Affiliation:** Tulane University Health Sciences Center **Investigator Full Name:** Franck Mauvais-Jarvis **Investigator Title:** Professor of Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The goal of this pilot clinical study is to perform a randomized placebo-controlled study to assess the beneficial effect of a 3 month-treatment with Bazedoxifene/Conjugated Estrogens (BZA/CE) vs. placebo on glucose homeostasis and body composition in 20 post-menopausal women. The recruitment will be performed at Tulane Health Sciences Center. ### Conditions Module **Conditions:** - Obesity - Glucose Homeostasis - Postmenopausal Symptoms ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 17 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants assigned to BZA/CE will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. BZA/CE (bazedoxifene/conjugated estrogens) tablets, 0.45 mg/20 mg are oval, biconvex, pink tablets, branded with "0.45/20" in black ink on one side. The recommended and only FDA approved dosage is one BZA/CE tablet daily, taken without regard to meals. Tablets should be swallowed whole. If a dose of BZA/CE is missed, participants will be instructed to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. The dose is one tablet per day independent of weight and fat mass. Participants will be provided with information about BZA/CE and its potential side effects and contraindications. **Intervention Names:** - Drug: Bazedoxifene/Conjugated Estrogens (BZA/CE) **Label:** Bazedoxifene/Conjugated Estrogens (BZA/CE) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants assigned to placebo will receive a daily tablet that matches the BZA/CE to maintain the blind. Placebo tablets, 0.45 mg/20 mg are oval, biconvex, pink tablets, branded with "0.45/20" in black ink on one side. Also to assure the blind is maintain, participants in the placebo group will be given the same instructions for taking the study medication.Tablets should be swallowed whole. If a dose, participants will be instructed to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. The dose is one tablet per day independent of weight and fat mass. Participants will be provided with information about BZA/CE and its potential side effects and contraindications, again to maintain the blind. **Intervention Names:** - Drug: Placebo Oral Tablet **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Bazedoxifene/Conjugated Estrogens (BZA/CE) **Description:** Daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **Name:** Bazedoxifene/Conjugated Estrogens (BZA/CE) **Other Names:** - DUAVEE **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Daily placebo tablet **Name:** Placebo Oral Tablet **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Body composition will be assessed through change in body mass index at baseline and at 3 months post-treatment. **Measure:** Change in Body Mass Index **Time Frame:** Change at 3 months from baseline **Description:** Body composition will be assessed through change in waist-to-hip ratio at baseline and at 3 months post-treatment. **Measure:** Effect of CE/BZA on Body Composition Using Waist-to-hip Ratio **Time Frame:** Change at 3 months from baseline **Description:** Dual-Energy X-ray Absorptiometry was used to assess body composition. DXA uses an x-ray technique to look at the density of the body and can then estimate the amount of lean muscle mass and fat tissue. Body composition will be assessed through change in DXA body composition at baseline and at 3 months post-treatment. **Measure:** Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA) **Time Frame:** Change at 3 months from baseline **Description:** This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in acute insulin response to glucose. IVGTT data derived by MINMOD Millennium software. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Acute Insulin Response (AIRg) to Intravenous Glucose is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection following glucose administration. A low AIRg indicates decreased ability of the pancreas to secrete insulin. **Measure:** Change in Acute Insulin Response to Glucose (AIRg) **Time Frame:** Change at 3 months from baseline **Description:** This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in basal glucose concentration. IVGTT data derived by MINMOD Millennium software. **Measure:** Change in Basal Glucose Concentration (Gb) **Time Frame:** Change at 3 months from baseline **Description:** Disposition index (DI) is the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. DI is commonly used as a measure of β-cell function. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in disposition index (DI). IVGTT data derived by MINMOD Millennium software. DI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. DI is the product of insulin sensitivity and the amount of insulin secreted in response to blood glucose levels. Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. A low DI is indicative of a higher risk of developing diabetes. **Measure:** Change in Disposition Index (DI) **Time Frame:** Change at 3 months from baseline **Description:** SI indicates the net capacity for insulin to promote the disposal of glucose and to inhibit the endogenous production of glucose. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in insulin sensitivity (SI) index. IVGTT data derived by MINMOD Millennium software. SI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. SI is a measure of tissue response to circulating insulin in the blood following glucose injection. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity. **Measure:** Change in Insulin Sensitivity (SI) Index **Time Frame:** Change at 3 months from baseline **Description:** The homeostasis model assessment of β-cell function (HOMA-β) is an index of insulin secretory function derived from fasting plasma glucose and insulin concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) β-cell function. (HOMA) β-cell function is a method used to quantify beta-cell function from fasting blood samples of insulin and glucose. Normal levels for (HOMA) β-cell function is 107 or more. Lower numbers mean higher risk of developing diabetes. **Measure:** Change in Homeostatic Model Assessment (HOMA) β-cell Function **Time Frame:** Change at 3 months from baseline **Description:** Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) insulin resistance. HOMA IR is a method used to quantify insulin resistance from fasting blood samples of insulin and glucose. Normal levels for HOMA-IR is less than 2.0. Higher levels mean higher risk for developing diabetes. **Measure:** Change in Homeostatic Model Assessment (HOMA) Insulin Resistance (IR) **Time Frame:** Change at 3 months from baseline **Description:** This will be assessed at baseline and 3 months to measure the change in fasting insulin clearance (FIC). FIC derived from fasting C-peptide to insulin ratio. **Measure:** Change in Fasting Insulin Clearance (FIC) **Time Frame:** Change at 3 months from baseline **Description:** This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in glucose-stimulated insulin clearance (GSIC). GSIC derived from molar ratio of C-peptide to insulin area under curve (AUC) over first 20 min of IVGTT. **Measure:** Change in Glucose-stimulated Insulin Clearance (GSIC) **Time Frame:** Change at 3 months from baseline #### Secondary Outcomes **Description:** Systematic inflammation will be measured through change in serum biomarkers (Leptin, Lipocalin 2 (LCN2), plasminogen activator inhibitor-1 (PAI-1), Intact OCN) taken at baseline and 3 months. **Measure:** Measure Change in Serum Biomarkers Panel 1 **Time Frame:** Change at 3 months from baseline **Description:** Systematic inflammation will be measured through change in serum biomarkers (Adiponectin, RBP4) taken at baseline and 3 months. **Measure:** Measure Change in Serum Biomarkers Panel 2 **Time Frame:** Change at 3 months from baseline **Description:** Systematic inflammation will be measured through change in leptin:adiponectin ratio (LAR) taken at baseline and 3 months. **Measure:** Measure Change in Leptin:Adiponectin Ratio (LAR) **Time Frame:** Change at 3 months from baseline **Description:** Systematic inflammation will be measured through change in Fibroblast growth factor-21 (FGF-21) taken at baseline and 3 months. **Measure:** Measure Change in Fibroblast Growth Factor-21 (FGF-21) **Time Frame:** Change at 3 months from baseline **Description:** Systematic inflammation will be measured through change in C-Reactive Protein (CRP) taken at baseline and 3 months. **Measure:** Measure Change in C-Reactive Protein (CRP) **Time Frame:** Change at 3 months from baseline **Description:** Systematic inflammation will be measured through change in Thiobarbituric acid reactive substance (TBARS) taken at baseline and 3 months. **Measure:** Measure Change in Thiobarbituric Acid Reactive Substance (TBARS) **Time Frame:** Change at 3 months from baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Post-menopausal women (\<5y since final menstrual period) with age between 50-60y * Symptomatic (hot flashes, vaginal dryness) or asymptomatic * BMI 26-45 kg/m2 (Overweight, Obesity I and Obesity II) * Fasting glucose \<125mg/dl * Triglycerides \<200mg/dl * Normal mammogram within past 12 months * Physician clearance Exclusion Criteria: * Amenorrhea from other causes (Hyperandrogenemia and anovulation) * type 2 and type 1 diabetes * Medications: diabetes or diabetic drugs, dyslipidemia, estrogen/progestin therapy, antidepressants and antipsychotics, antiretroviral (HIV), oral steroids, weight loss drugs * ≤ 3 month washout of birth control pill (often prescribed for postmenopausal symptoms) * Hysterectomy (partial or complete) * Contraindications to estrogen treatment (unusual vaginal bleeding, blot clots, hepatic disease, bleeding disorder, past/present history of breast or uterine cancer, pregnant, breastfeeding) **Maximum Age:** 60 Years **Minimum Age:** 50 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New Orleans **Country:** United States **Facility:** Tulane University Clinical Translational Unit **State:** Louisiana **Zip:** 70112 #### Overall Officials **Official 1:** **Affiliation:** Tulane University **Name:** Franck Mauvais-Jarvis, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** At this time there is no plan to share individual participant data (IPD) **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2017-07-26 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 515088 - Type Abbrev: Prot_SAP - Upload Date: 2023-02-27T10:11 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000020845 - Term: Selective Estrogen Receptor Modulators - ID: D000020847 - Term: Estrogen Receptor Modulators - ID: D000006727 - Term: Hormone Antagonists - ID: D000050071 - Term: Bone Density Conservation Agents ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M8116 - Name: Estrogens - Relevance: HIGH - As Found: Interviewing - ID: M8115 - Name: Estrogens, Conjugated (USP) - Relevance: HIGH - As Found: Childhood Obesity - ID: M4854 - Name: Benzocaine - Relevance: LOW - As Found: Unknown - ID: M215342 - Name: Bazedoxifene - Relevance: HIGH - As Found: Former - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M22599 - Name: Estrogen Receptor Modulators - Relevance: LOW - As Found: Unknown - ID: M22597 - Name: Selective Estrogen Receptor Modulators - Relevance: LOW - As Found: Unknown - ID: T433 - Name: Tannic Acid - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000447119 - Term: Bazedoxifene - ID: D000004967 - Term: Estrogens - ID: D000004966 - Term: Estrogens, Conjugated (USP) ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) **Deaths Num At Risk:** 7 **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** EG000 **Other Num at Risk:** 7 **Serious Number At Risk:** 7 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) **Group ID:** EG001 **Title:** Placebo **Deaths Num At Risk:** 5 **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** EG001 **Other Num Affected:** 1 **Other Num at Risk:** 5 **Serious Number At Risk:** 5 **Title:** Placebo **Frequency Threshold:** 0 #### Other Events **Term:** Lower Insulin dose given **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** During the preparations for IVGTT, incorrect (lower) weight of the subject was used to calculate insulin dose, therefore patient was given lower than recommended insulin dose during IVGTT. This event did not affect patient's wellbeing or health. **Organ System:** Endocrine disorders **Source Vocabulary:** **Time Frame:** The data were collected during baseline visit (during IVGTT for 3 hours) and then again they were collected at the 3 months visit (during IVGTT for 3 hours). ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 7 **Group ID:** BG001 **Value:** 5 **Group ID:** BG002 **Value:** 12 **Units:** Participants ### Group **ID:** BG000 **Title:** Conjugated Estrogens/Bazedoxifene (CE/BZA) **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. ### Group **ID:** BG001 **Title:** Placebo **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. ### 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:** 7 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 12 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 52 **Upper Limit:** 56 **Value:** 54 #### Measurement **Group ID:** BG001 **Lower Limit:** 54 **Upper Limit:** 58 **Value:** 55 #### Measurement **Group ID:** BG002 **Lower Limit:** 53 **Upper Limit:** 56.5 **Value:** 54.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 12 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 10 **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:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 12 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 1.4 **Upper Limit:** 3.8 **Value:** 2 #### Measurement **Group ID:** BG001 **Lower Limit:** 2.1 **Upper Limit:** 4.8 **Value:** 4.5 #### Measurement **Group ID:** BG002 **Lower Limit:** 1.7 **Upper Limit:** 4.4 **Value:** 2.7 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 0.82 **Upper Limit:** 0.95 **Value:** 0.9 #### Measurement **Group ID:** BG001 **Lower Limit:** 0.82 **Upper Limit:** 0.85 **Value:** 0.84 #### Measurement **Group ID:** BG002 **Lower Limit:** 0.82 **Upper Limit:** 0.94 **Value:** 0.85 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 30.6 **Upper Limit:** 37 **Value:** 33 #### Measurement **Group ID:** BG001 **Lower Limit:** 30.7 **Upper Limit:** 38.6 **Value:** 31.2 #### Measurement **Group ID:** BG002 **Lower Limit:** 30.7 **Upper Limit:** 37.8 **Value:** 32.4 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 91.4 **Upper Limit:** 114.3 **Value:** 109.2 #### Measurement **Group ID:** BG001 **Lower Limit:** 92 **Upper Limit:** 116.8 **Value:** 106.7 #### Measurement **Group ID:** BG002 **Lower Limit:** 91.7 **Upper Limit:** 115.6 **Value:** 108 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 83 **Upper Limit:** 114 **Value:** 94 #### Measurement **Group ID:** BG001 **Lower Limit:** 84 **Upper Limit:** 98 **Value:** 88 #### Measurement **Group ID:** BG002 **Lower Limit:** 83.5 **Upper Limit:** 108 **Value:** 93.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 167 **Upper Limit:** 218 **Value:** 208 #### Measurement **Group ID:** BG001 **Lower Limit:** 202 **Upper Limit:** 245 **Value:** 216 #### Measurement **Group ID:** BG002 **Lower Limit:** 190.5 **Upper Limit:** 231.5 **Value:** 211.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 45 **Upper Limit:** 69 **Value:** 60 #### Measurement **Group ID:** BG001 **Lower Limit:** 58 **Upper Limit:** 73 **Value:** 66 #### Measurement **Group ID:** BG002 **Lower Limit:** 49.5 **Upper Limit:** 71 **Value:** 63 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 99 **Upper Limit:** 148 **Value:** 120 #### Measurement **Group ID:** BG001 **Lower Limit:** 115 **Upper Limit:** 147 **Value:** 128 #### Measurement **Group ID:** BG002 **Lower Limit:** 111.5 **Upper Limit:** 147.5 **Value:** 124 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 81 **Upper Limit:** 131 **Value:** 124 #### Measurement **Group ID:** BG001 **Lower Limit:** 102 **Upper Limit:** 125 **Value:** 103 #### Measurement **Group ID:** BG002 **Lower Limit:** 82.5 **Upper Limit:** 128.5 **Value:** 113.5 **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:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **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:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Years since last menstrual period (LMP) **Unit of Measure:** Years ### Measure 7 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Waist-to-hip ratio **Unit of Measure:** Ratio ### Measure 8 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Body Mass Index (BMI) **Unit of Measure:** Kg/m^2 ### Measure 9 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Waist circumference **Unit of Measure:** Cm ### Measure 10 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Fasting glucose **Unit of Measure:** mg/dL ### Measure 11 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Total cholesterol **Unit of Measure:** mg/dL ### Measure 12 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** High-density lipoprotein (HDL) **Unit of Measure:** mg/dL ### Measure 13 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Low-density lipoprotein (LDL) **Unit of Measure:** mg/dL ### Measure 14 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Triglycerides **Unit of Measure:** mg/dL ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Tulane University **Phone:** 504-988-5990 **Title:** Dr. Franck Mauvais-Jarvis ## 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 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.5 - **Spread:** - **Upper Limit:** 0.3 - **Value:** -0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.6 - **Spread:** - **Upper Limit:** -0.3 - **Value:** -0.5 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.06 - **Spread:** - **Upper Limit:** 0.03 - **Value:** -0.05 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.02 - **Spread:** - **Upper Limit:** 0.00 - **Value:** 0.00 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -571 - **Spread:** - **Upper Limit:** 974 - **Value:** 273 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -1932 - **Spread:** - **Upper Limit:** 467 - **Value:** -1408 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -226 - **Spread:** - **Upper Limit:** 611 - **Value:** 1.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -452 - **Spread:** - **Upper Limit:** -86 - **Value:** -131 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -550 - **Spread:** - **Upper Limit:** 279 - **Value:** -26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -189 - **Spread:** - **Upper Limit:** -116 - **Value:** -178 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -63 - **Spread:** - **Upper Limit:** 118 - **Value:** 46 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -134 - **Spread:** - **Upper Limit:** -23 - **Value:** -47 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -31 - **Spread:** - **Upper Limit:** 444 - **Value:** 189 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -47 - **Spread:** - **Upper Limit:** -9 - **Value:** -25 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -9.2 - **Spread:** - **Upper Limit:** -1.7 - **Value:** -5.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.9 - **Spread:** - **Upper Limit:** 4.9 - **Value:** 2.7 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -19 - **Spread:** - **Upper Limit:** 841 - **Value:** 500 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 28 - **Spread:** - **Upper Limit:** 572 - **Value:** 267 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -1.50 - **Spread:** - **Upper Limit:** 0.19 - **Value:** -0.24 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1.12 - **Spread:** - **Upper Limit:** 1.82 - **Value:** 1.35 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.9 - **Spread:** - **Upper Limit:** 320.6 - **Value:** 18.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -39.9 - **Spread:** - **Upper Limit:** 0.1 - **Value:** -25.5 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.18 - **Spread:** - **Upper Limit:** 0.34 - **Value:** 0.15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.10 - **Spread:** - **Upper Limit:** 0.24 - **Value:** -0.01 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -11.56 - **Spread:** - **Upper Limit:** 0.78 - **Value:** -3.50 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.70 - **Spread:** - **Upper Limit:** -0.00 - **Value:** -0.25 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -123.6 - **Spread:** - **Upper Limit:** 6.9 - **Value:** -32.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -20.5 - **Spread:** - **Upper Limit:** 25.8 - **Value:** -1.85 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -7.2 - **Spread:** - **Upper Limit:** 9.5 - **Value:** -1.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.1 - **Spread:** - **Upper Limit:** 10.5 - **Value:** 0.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -3 - **Spread:** - **Upper Limit:** 3.5 - **Value:** -1.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -4.9 - **Spread:** - **Upper Limit:** 2.2 - **Value:** -3.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -5.2 - **Spread:** - **Upper Limit:** -1.4 - **Value:** -1.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.4 - **Spread:** - **Upper Limit:** 3.3 - **Value:** 1.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.7 - **Spread:** - **Upper Limit:** 3.1 - **Value:** 0.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -1.1 - **Spread:** - **Upper Limit:** 2.7 - **Value:** -0.9 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -5.6 - **Spread:** - **Upper Limit:** 14.5 - **Value:** -0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -24.1 - **Spread:** - **Upper Limit:** 4.6 - **Value:** -4.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.8 - **Spread:** - **Upper Limit:** -0.5 - **Value:** -1.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -2.6 - **Spread:** - **Upper Limit:** -0.4 - **Value:** -2.5 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.04 - **Spread:** - **Upper Limit:** 4.96 - **Value:** 2.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.02 - **Spread:** - **Upper Limit:** 4.03 - **Value:** 1.55 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -208 - **Spread:** - **Upper Limit:** 24 - **Value:** -134 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -226 - **Spread:** - **Upper Limit:** -48 - **Value:** -89 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.66 - **Spread:** - **Upper Limit:** 0.45 - **Value:** -0.41 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.82 - **Spread:** - **Upper Limit:** -0.06 - **Value:** -0.39 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -3.3 - **Spread:** - **Upper Limit:** -0.4 - **Value:** -1.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -1.2 - **Spread:** - **Upper Limit:** 0.0 - **Value:** -1.2 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Body composition will be assessed through change in body mass index at baseline and at 3 months post-treatment. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Body Mass Index **Type:** PRIMARY **Unit of Measure:** Kg/m^2 ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 2 **Description:** Body composition will be assessed through change in waist-to-hip ratio at baseline and at 3 months post-treatment. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Effect of CE/BZA on Body Composition Using Waist-to-hip Ratio **Type:** PRIMARY **Unit of Measure:** Ratio ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 3 **Description:** Dual-Energy X-ray Absorptiometry was used to assess body composition. DXA uses an x-ray technique to look at the density of the body and can then estimate the amount of lean muscle mass and fat tissue. Body composition will be assessed through change in DXA body composition at baseline and at 3 months post-treatment. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA) **Type:** PRIMARY **Unit of Measure:** g ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 4 **Description:** This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in acute insulin response to glucose. IVGTT data derived by MINMOD Millennium software. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Acute Insulin Response (AIRg) to Intravenous Glucose is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection following glucose administration. A low AIRg indicates decreased ability of the pancreas to secrete insulin. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6). **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Acute Insulin Response to Glucose (AIRg) **Type:** PRIMARY **Unit of Measure:** uU/l^-1.min^-1 ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 5 **Description:** This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in basal glucose concentration. IVGTT data derived by MINMOD Millennium software. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6). **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Basal Glucose Concentration (Gb) **Type:** PRIMARY **Unit of Measure:** mg/dL ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 6 **Description:** Disposition index (DI) is the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. DI is commonly used as a measure of β-cell function. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in disposition index (DI). IVGTT data derived by MINMOD Millennium software. DI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. DI is the product of insulin sensitivity and the amount of insulin secreted in response to blood glucose levels. Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. A low DI is indicative of a higher risk of developing diabetes. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6). **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Disposition Index (DI) **Type:** PRIMARY **Unit of Measure:** Index ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 7 **Description:** SI indicates the net capacity for insulin to promote the disposal of glucose and to inhibit the endogenous production of glucose. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in insulin sensitivity (SI) index. IVGTT data derived by MINMOD Millennium software. SI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. SI is a measure of tissue response to circulating insulin in the blood following glucose injection. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6). **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Insulin Sensitivity (SI) Index **Type:** PRIMARY **Unit of Measure:** uU/L^-1.min^-1 ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 8 **Description:** The homeostasis model assessment of β-cell function (HOMA-β) is an index of insulin secretory function derived from fasting plasma glucose and insulin concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) β-cell function. (HOMA) β-cell function is a method used to quantify beta-cell function from fasting blood samples of insulin and glucose. Normal levels for (HOMA) β-cell function is 107 or more. Lower numbers mean higher risk of developing diabetes. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6). **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Homeostatic Model Assessment (HOMA) β-cell Function **Type:** PRIMARY **Unit of Measure:** uU/mM ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 9 **Description:** Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) insulin resistance. HOMA IR is a method used to quantify insulin resistance from fasting blood samples of insulin and glucose. Normal levels for HOMA-IR is less than 2.0. Higher levels mean higher risk for developing diabetes. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6). **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Homeostatic Model Assessment (HOMA) Insulin Resistance (IR) **Type:** PRIMARY **Unit of Measure:** mM.uU/L^-2 ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 10 **Description:** This will be assessed at baseline and 3 months to measure the change in fasting insulin clearance (FIC). FIC derived from fasting C-peptide to insulin ratio. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6). **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Fasting Insulin Clearance (FIC) **Type:** PRIMARY **Unit of Measure:** Ratio ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 11 **Description:** This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in glucose-stimulated insulin clearance (GSIC). GSIC derived from molar ratio of C-peptide to insulin area under curve (AUC) over first 20 min of IVGTT. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6). **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Change in Glucose-stimulated Insulin Clearance (GSIC) **Type:** PRIMARY **Unit of Measure:** Ratio ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 12 **Description:** Systematic inflammation will be measured through change in serum biomarkers (Leptin, Lipocalin 2 (LCN2), plasminogen activator inhibitor-1 (PAI-1), Intact OCN) taken at baseline and 3 months. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Measure Change in Serum Biomarkers Panel 1 **Type:** SECONDARY **Unit of Measure:** ng/mL ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 13 **Description:** Systematic inflammation will be measured through change in serum biomarkers (Adiponectin, RBP4) taken at baseline and 3 months. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Measure Change in Serum Biomarkers Panel 2 **Type:** SECONDARY **Unit of Measure:** ug/mL ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 14 **Description:** Systematic inflammation will be measured through change in leptin:adiponectin ratio (LAR) taken at baseline and 3 months. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Measure Change in Leptin:Adiponectin Ratio (LAR) **Type:** SECONDARY **Unit of Measure:** Ratio ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 15 **Description:** Systematic inflammation will be measured through change in Fibroblast growth factor-21 (FGF-21) taken at baseline and 3 months. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Measure Change in Fibroblast Growth Factor-21 (FGF-21) **Type:** SECONDARY **Unit of Measure:** pg/mL ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 16 **Description:** Systematic inflammation will be measured through change in C-Reactive Protein (CRP) taken at baseline and 3 months. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Measure Change in C-Reactive Protein (CRP) **Type:** SECONDARY **Unit of Measure:** mg/mL ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo #### Outcome Measure 17 **Description:** Systematic inflammation will be measured through change in Thiobarbituric acid reactive substance (TBARS) taken at baseline and 3 months. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Change at 3 months from baseline **Title:** Measure Change in Thiobarbituric Acid Reactive Substance (TBARS) **Type:** SECONDARY **Unit of Measure:** nmol/mL ##### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** OG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) ##### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** OG001 **Title:** Placebo ### Participant Flow Module #### Group **Description:** Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. **ID:** FG000 **Title:** Bazedoxifene/Conjugated Estrogens (CE/BZA) #### Group **Description:** Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind. **ID:** FG001 **Title:** Placebo #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 10 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 7 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 7 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 5 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00898079 **Brief Title:** Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer **Official Title:** A Children's Oncology Group Protocol for Collecting and Banking Pediatric Research Specimens Including Rare Pediatric Tumors **NCT ID Aliases:** - NCT00228735 #### Organization Study ID Info **ID:** ABTR01B1 #### Organization **Class:** NETWORK **Full Name:** Children's Oncology Group #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2009-00324 **Type:** REGISTRY **ID:** CDR0000271415 **ID:** COG-ABTR01B1 **Domain:** Childrens Oncology Group **ID:** ABTR01B1 **Type:** OTHER **Domain:** CTEP **ID:** ABTR01B1 **Type:** OTHER **ID:** U10CA098543 **Link:** https://reporter.nih.gov/quickSearch/U10CA098543 **Type:** NIH **ID:** UG1CA189958 **Link:** https://reporter.nih.gov/quickSearch/UG1CA189958 **Type:** NIH ### Status Module #### Completion Date **Date:** 2018-06-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-07-19 **Type:** ACTUAL **Last Update Submit Date:** 2018-07-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-06-30 **Type:** ACTUAL #### Start Date **Date:** 2003-10-13 **Type:** ACTUAL **Status Verified Date:** 2018-07 #### Study First Post Date **Date:** 2009-05-12 **Type:** ESTIMATED **Study First Submit Date:** 2009-05-09 **Study First Submit QC Date:** 2009-05-09 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### Lead Sponsor **Class:** NETWORK **Name:** Children's Oncology Group #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This study is collecting and storing malignant, borderline malignant neoplasms, and related biological samples from young patients with cancer. Collecting and storing samples of tumor tissue, blood, and bone marrow from patients with cancer to study in the laboratory may help the study of cancer in the future. **Detailed Description:** OBJECTIVES: I. Collect malignant, borderline malignant neoplasms, and related biological specimens from Children's Oncology Group institutions for cases in which there is no disease-specific biologic protocol. II. Provide a repository for long-term storage of malignant, borderline malignant neoplasms, and related biological specimens from these patients. III. Make specimens available to qualified researchers to understand the biology of cancer in these patients. OUTLINE: Tumor tissue samples, blood, and bone marrow aspirates are collected and stored for future analysis. ### Conditions Module **Conditions:** - Acute Undifferentiated Leukemia - Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative - Childhood Acute Lymphoblastic Leukemia - Childhood Acute Myeloid Leukemia - Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive - Childhood Solid Neoplasm - Chronic Lymphocytic Leukemia - Hairy Cell Leukemia - Juvenile Myelomonocytic Leukemia - Mast Cell Leukemia - Neoplasm of Uncertain Malignant Potential - Prolymphocytic Leukemia - Secondary Acute Myeloid Leukemia - T-Cell Large Granular Lymphocyte Leukemia ### Design Module #### Enrollment Info **Count:** 2545 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Tumor tissue samples, blood, and bone marrow aspirates are collected and stored for future analysis. **Intervention Names:** - Other: Cytology Specimen Collection Procedure **Label:** Observational ### Interventions #### Intervention 1 **Arm Group Labels:** - Observational **Description:** Correlative studies **Name:** Cytology Specimen Collection Procedure **Other Names:** - Cytologic Sampling **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** Repository of malignant, borderline malignant neoplasms, and related biological specimens **Time Frame:** Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Meets any of the following criteria: * Diagnosed with primary neoplasm * Developed a second malignant neoplasm * Any diagnoses having an ICD-O Morphology Code ending in 1, 2, or 3 as listed in the International Classification of Disease for Oncology, Third Edition * Must have biological specimens including solid tumors and leukemias available * Solid tumors meeting the following criteria: * Snap frozen primary tumor OR OCT embedded primary tumor OR formalin fixed (block or tissue in formalin) primary tumor AND at least 10 unstained paraffin slides for NIH Mandated QC (tumors that have undergone central pathology review are allowed) * Slides for pathology review (instead of slides for QC) are required for patients with rare tumors * Pleural fluid or cytologic specimens meeting the following criteria: * At least 1 mL of fluid and at least 2 unstained cytospin slides (or 2 unstained smears) * Slides for pathology review (instead of slides for QC) are required for patients with rare tumors * ALL/AML * 3-6 mL of bone marrow aspirate and 10 mL of whole blood * Not eligible for disease-specific biology or banking protocol **Maximum Age:** 30 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** Children's Hospital of Alabama **State:** Alabama **Zip:** 35233 **Location 2:** **City:** Birmingham **Country:** United States **Facility:** University of Alabama at Birmingham Cancer Center **State:** Alabama **Zip:** 35233 **Location 3:** **City:** Phoenix **Country:** United States **Facility:** Phoenix Childrens Hospital **State:** Arizona **Zip:** 85016 **Location 4:** **City:** Little Rock **Country:** United States **Facility:** Arkansas Children's Hospital **State:** Arkansas **Zip:** 72202-3591 **Location 5:** **City:** Little Rock **Country:** United States **Facility:** University of Arkansas for Medical Sciences **State:** Arkansas **Zip:** 72205 **Location 6:** **City:** Downey **Country:** United States **Facility:** Kaiser Permanente Downey Medical Center **State:** California **Zip:** 90242 **Location 7:** **City:** Duarte **Country:** United States **Facility:** City of Hope Comprehensive Cancer Center **State:** California **Zip:** 91010 **Location 8:** **City:** Loma Linda **Country:** United States **Facility:** Loma Linda University Medical Center **State:** California **Zip:** 92354 **Location 9:** **City:** Long Beach **Country:** United States **Facility:** Miller Children's and Women's Hospital Long Beach **State:** California **Zip:** 90806 **Location 10:** **City:** Los Angeles **Country:** United States **Facility:** Children's Hospital Los Angeles **State:** California **Zip:** 90027 **Location 11:** **City:** Los Angeles **Country:** United States **Facility:** Cedars Sinai Medical Center **State:** California **Zip:** 90048 **Location 12:** **City:** Los Angeles **Country:** United States **Facility:** Mattel Children's Hospital UCLA **State:** California **Zip:** 90095 **Location 13:** **City:** Los Angeles **Country:** United States **Facility:** UCLA / Jonsson Comprehensive Cancer Center **State:** California **Zip:** 90095 **Location 14:** **City:** Madera **Country:** United States **Facility:** Children's Hospital Central California **State:** California **Zip:** 93636-8762 **Location 15:** **City:** Oakland **Country:** United States **Facility:** Children's Hospital and Research Center at Oakland **State:** California **Zip:** 94609-1809 **Location 16:** **City:** Oakland **Country:** United States **Facility:** Kaiser Permanente-Oakland **State:** California **Zip:** 94611 **Location 17:** **City:** Orange **Country:** United States **Facility:** Children's Hospital of Orange County **State:** California **Zip:** 92868 **Location 18:** **City:** Palo Alto **Country:** United States **Facility:** Lucile Packard Children's Hospital Stanford University **State:** California **Zip:** 94304 **Location 19:** **City:** San Diego **Country:** United States **Facility:** Rady Children's Hospital - San Diego **State:** California **Zip:** 92123 **Location 20:** **City:** San Francisco **Country:** United States **Facility:** UCSF Medical Center-Parnassus **State:** California **Zip:** 94143 **Location 21:** **City:** San Francisco **Country:** United States **Facility:** UCSF Medical Center-Mission Bay **State:** California **Zip:** 94158 **Location 22:** **City:** Aurora **Country:** United States **Facility:** Children's Hospital Colorado **State:** Colorado **Zip:** 80045 **Location 23:** **City:** Denver **Country:** United States **Facility:** Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center **State:** Colorado **Zip:** 80218 **Location 24:** **City:** Hartford **Country:** United States **Facility:** Connecticut Children's Medical Center **State:** Connecticut **Zip:** 06106 **Location 25:** **City:** Wilmington **Country:** United States **Facility:** Alfred I duPont Hospital for Children **State:** Delaware **Zip:** 19803 **Location 26:** **City:** Washington **Country:** United States **Facility:** MedStar Georgetown University Hospital **State:** District of Columbia **Zip:** 20007 **Location 27:** **City:** Washington **Country:** United States **Facility:** Children's National Medical Center **State:** District of Columbia **Zip:** 20010 **Location 28:** **City:** Fort Lauderdale **Country:** United States **Facility:** Broward Health Medical Center **State:** Florida **Zip:** 33316 **Location 29:** **City:** Fort Myers **Country:** United States **Facility:** Lee Memorial Health System **State:** Florida **Zip:** 33901 **Location 30:** **City:** Fort Myers **Country:** United States **Facility:** Golisano Children's Hospital of Southwest Florida **State:** Florida **Zip:** 33908 **Location 31:** **City:** Gainesville **Country:** United States **Facility:** University of Florida Health Science Center - Gainesville **State:** Florida **Zip:** 32610 **Location 32:** **City:** Hollywood **Country:** United States **Facility:** Memorial Regional Hospital/Joe DiMaggio Children's Hospital **State:** Florida **Zip:** 33021 **Location 33:** **City:** Jacksonville **Country:** United States **Facility:** Nemours Children's Clinic-Jacksonville **State:** Florida **Zip:** 32207 **Location 34:** **City:** Miami **Country:** United States **Facility:** University of Miami Miller School of Medicine-Sylvester Cancer Center **State:** Florida **Zip:** 33136 **Location 35:** **City:** Miami **Country:** United States **Facility:** Nicklaus Children's Hospital **State:** Florida **Zip:** 33155 **Location 36:** **City:** Miami **Country:** United States **Facility:** Miami Cancer Institute **State:** Florida **Zip:** 33176 **Location 37:** **City:** Orlando **Country:** United States **Facility:** Florida Hospital Orlando **State:** Florida **Zip:** 32803 **Location 38:** **City:** Orlando **Country:** United States **Facility:** Nemours Children's Clinic - Orlando **State:** Florida **Zip:** 32806 **Location 39:** **City:** Orlando **Country:** United States **Facility:** Nemours Children's Hospital **State:** Florida **Zip:** 32827 **Location 40:** **City:** Pensacola **Country:** United States **Facility:** Nemours Children's Clinic - Pensacola **State:** Florida **Zip:** 32504 **Location 41:** **City:** Saint Petersburg **Country:** United States **Facility:** Johns Hopkins All Children's Hospital **State:** Florida **Zip:** 33701 **Location 42:** **City:** Tampa **Country:** United States **Facility:** Tampa General Hospital **State:** Florida **Zip:** 33606 **Location 43:** **City:** Tampa **Country:** United States **Facility:** Saint Joseph's Hospital/Children's Hospital-Tampa **State:** Florida **Zip:** 33607 **Location 44:** **City:** West Palm Beach **Country:** United States **Facility:** Saint Mary's Hospital **State:** Florida **Zip:** 33407 **Location 45:** **City:** Atlanta **Country:** United States **Facility:** Children's Healthcare of Atlanta - Egleston **State:** Georgia **Zip:** 30322 **Location 46:** **City:** Savannah **Country:** United States **Facility:** Memorial Health University Medical Center **State:** Georgia **Zip:** 31404 **Location 47:** **City:** Honolulu **Country:** United States **Facility:** University of Hawaii Cancer Center **State:** Hawaii **Zip:** 96813 **Location 48:** **City:** Honolulu **Country:** United States **Facility:** Kapiolani Medical Center for Women and Children **State:** Hawaii **Zip:** 96826 **Location 49:** **City:** Boise **Country:** United States **Facility:** Saint Luke's Mountain States Tumor Institute **State:** Idaho **Zip:** 83712 **Location 50:** **City:** Chicago **Country:** United States **Facility:** Lurie Children's Hospital-Chicago **State:** Illinois **Zip:** 60611 **Location 51:** **City:** Chicago **Country:** United States **Facility:** University of Illinois **State:** Illinois **Zip:** 60612 **Location 52:** **City:** Chicago **Country:** United States **Facility:** University of Chicago Comprehensive Cancer Center **State:** Illinois **Zip:** 60637 **Location 53:** **City:** Maywood **Country:** United States **Facility:** Loyola University Medical Center **State:** Illinois **Zip:** 60153 **Location 54:** **City:** Park Ridge **Country:** United States **Facility:** Advocate Children's Hospital-Park Ridge **State:** Illinois **Zip:** 60068 **Location 55:** **City:** Park Ridge **Country:** United States **Facility:** Advocate Lutheran General Hospital **State:** Illinois **Zip:** 60068 **Location 56:** **City:** Peoria **Country:** United States **Facility:** Saint Jude Midwest Affiliate **State:** Illinois **Zip:** 61637 **Location 57:** **City:** Springfield **Country:** United States **Facility:** Southern Illinois University School of Medicine **State:** Illinois **Zip:** 62702 **Location 58:** **City:** Indianapolis **Country:** United States **Facility:** Riley Hospital for Children **State:** Indiana **Zip:** 46202 **Location 59:** **City:** Indianapolis **Country:** United States **Facility:** Saint Vincent Hospital and Health Care Center **State:** Indiana **Zip:** 46260 **Location 60:** **City:** Des Moines **Country:** United States **Facility:** Blank Children's Hospital **State:** Iowa **Zip:** 50309 **Location 61:** **City:** Iowa City **Country:** United States **Facility:** University of Iowa/Holden Comprehensive Cancer Center **State:** Iowa **Zip:** 52242 **Location 62:** **City:** Kansas City **Country:** United States **Facility:** University of Kansas Cancer Center **State:** Kansas **Zip:** 66160 **Location 63:** **City:** Lexington **Country:** United States **Facility:** University of Kentucky/Markey Cancer Center **State:** Kentucky **Zip:** 40536 **Location 64:** **City:** Louisville **Country:** United States **Facility:** Norton Children's Hospital **State:** Kentucky **Zip:** 40202 **Location 65:** **City:** New Orleans **Country:** United States **Facility:** Tulane University Health Sciences Center **State:** Louisiana **Zip:** 70112 **Location 66:** **City:** New Orleans **Country:** United States **Facility:** Children's Hospital New Orleans **State:** Louisiana **Zip:** 70118 **Location 67:** **City:** New Orleans **Country:** United States **Facility:** Ochsner Medical Center Jefferson **State:** Louisiana **Zip:** 70121 **Location 68:** **City:** Scarborough **Country:** United States **Facility:** Maine Children's Cancer Program **State:** Maine **Zip:** 04074 **Location 69:** **City:** Baltimore **Country:** United States **Facility:** Sinai Hospital of Baltimore **State:** Maryland **Zip:** 21215 **Location 70:** **City:** Bethesda **Country:** United States **Facility:** Walter Reed National Military Medical Center **State:** Maryland **Zip:** 20889-5600 **Location 71:** **City:** Boston **Country:** United States **Facility:** Dana-Farber Cancer Institute **State:** Massachusetts **Zip:** 02215 **Location 72:** **City:** Springfield **Country:** United States **Facility:** Baystate Medical Center **State:** Massachusetts **Zip:** 01199 **Location 73:** **City:** Ann Arbor **Country:** United States **Facility:** C S Mott Children's Hospital **State:** Michigan **Zip:** 48109 **Location 74:** **City:** Detroit **Country:** United States **Facility:** Wayne State University/Karmanos Cancer Institute **State:** Michigan **Zip:** 48201 **Location 75:** **City:** Detroit **Country:** United States **Facility:** Saint John Hospital and Medical Center **State:** Michigan **Zip:** 48236 **Location 76:** **City:** East Lansing **Country:** United States **Facility:** Michigan State University Clinical Center **State:** Michigan **Zip:** 48824-7016 **Location 77:** **City:** Flint **Country:** United States **Facility:** Hurley Medical Center **State:** Michigan **Zip:** 48503 **Location 78:** **City:** Grand Rapids **Country:** United States **Facility:** Helen DeVos Children's Hospital at Spectrum Health **State:** Michigan **Zip:** 49503 **Location 79:** **City:** Kalamazoo **Country:** United States **Facility:** Bronson Methodist Hospital **State:** Michigan **Zip:** 49007 **Location 80:** **City:** Kalamazoo **Country:** United States **Facility:** Kalamazoo Center for Medical Studies **State:** Michigan **Zip:** 49008 **Location 81:** **City:** Minneapolis **Country:** United States **Facility:** Children's Hospitals and Clinics of Minnesota - Minneapolis **State:** Minnesota **Zip:** 55404 **Location 82:** **City:** Minneapolis **Country:** United States **Facility:** University of Minnesota/Masonic Cancer Center **State:** Minnesota **Zip:** 55455 **Location 83:** **City:** Rochester **Country:** United States **Facility:** Mayo Clinic **State:** Minnesota **Zip:** 55905 **Location 84:** **City:** Jackson **Country:** United States **Facility:** University of Mississippi Medical Center **State:** Mississippi **Zip:** 39216 **Location 85:** **City:** Columbia **Country:** United States **Facility:** Columbia Regional **State:** Missouri **Zip:** 65201 **Location 86:** **City:** Kansas City **Country:** United States **Facility:** The Childrens Mercy Hospital **State:** Missouri **Zip:** 64108 **Location 87:** **City:** Saint Louis **Country:** United States **Facility:** Cardinal Glennon Children's Medical Center **State:** Missouri **Zip:** 63104 **Location 88:** **City:** Saint Louis **Country:** United States **Facility:** Washington University School of Medicine **State:** Missouri **Zip:** 63110 **Location 89:** **City:** Omaha **Country:** United States **Facility:** Children's Hospital and Medical Center of Omaha **State:** Nebraska **Zip:** 68114 **Location 90:** **City:** Omaha **Country:** United States **Facility:** University of Nebraska Medical Center **State:** Nebraska **Zip:** 68198 **Location 91:** **City:** Las Vegas **Country:** United States **Facility:** Nevada Cancer Research Foundation CCOP **State:** Nevada **Zip:** 89106 **Location 92:** **City:** Las Vegas **Country:** United States **Facility:** Children's Specialty Center of Nevada II **State:** Nevada **Zip:** 89109 **Location 93:** **City:** Las Vegas **Country:** United States **Facility:** Sunrise Hospital and Medical Center **State:** Nevada **Zip:** 89109 **Location 94:** **City:** Hackensack **Country:** United States **Facility:** Hackensack University Medical Center **State:** New Jersey **Zip:** 07601 **Location 95:** **City:** Livingston **Country:** United States **Facility:** Saint Barnabas Medical Center **State:** New Jersey **Zip:** 07039 **Location 96:** **City:** Morristown **Country:** United States **Facility:** Morristown Medical Center **State:** New Jersey **Zip:** 07960 **Location 97:** **City:** New Brunswick **Country:** United States **Facility:** Saint Peter's University Hospital **State:** New Jersey **Zip:** 08901 **Location 98:** **City:** New Brunswick **Country:** United States **Facility:** Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital **State:** New Jersey **Zip:** 08903 **Location 99:** **City:** Newark **Country:** United States **Facility:** Newark Beth Israel Medical Center **State:** New Jersey **Zip:** 07112 **Location 100:** **City:** Paterson **Country:** United States **Facility:** Saint Joseph's Regional Medical Center **State:** New Jersey **Zip:** 07503 **Location 101:** **City:** Summit **Country:** United States **Facility:** Overlook Hospital **State:** New Jersey **Zip:** 07902 **Location 102:** **City:** Albuquerque **Country:** United States **Facility:** University of New Mexico Cancer Center **State:** New Mexico **Zip:** 87102 **Location 103:** **City:** Albany **Country:** United States **Facility:** Albany Medical Center **State:** New York **Zip:** 12208 **Location 104:** **City:** Bronx **Country:** United States **Facility:** Montefiore Medical Center - Moses Campus **State:** New York **Zip:** 10467 **Location 105:** **City:** Brooklyn **Country:** United States **Facility:** Brooklyn Hospital Center **State:** New York **Zip:** 11201 **Location 106:** **City:** Brooklyn **Country:** United States **Facility:** Maimonides Medical Center **State:** New York **Zip:** 11219 **Location 107:** **City:** Buffalo **Country:** United States **Facility:** Roswell Park Cancer Institute **State:** New York **Zip:** 14263 **Location 108:** **City:** Mineola **Country:** United States **Facility:** NYU Winthrop Hospital **State:** New York **Zip:** 11501 **Location 109:** **City:** New Hyde Park **Country:** United States **Facility:** The Steven and Alexandra Cohen Children's Medical Center of New York **State:** New York **Zip:** 11040 **Location 110:** **City:** New York **Country:** United States **Facility:** Laura and Isaac Perlmutter Cancer Center at NYU Langone **State:** New York **Zip:** 10016 **Location 111:** **City:** New York **Country:** United States **Facility:** Mount Sinai Hospital **State:** New York **Zip:** 10029 **Location 112:** **City:** New York **Country:** United States **Facility:** Columbia University/Herbert Irving Cancer Center **State:** New York **Zip:** 10032 **Location 113:** **City:** Rochester **Country:** United States **Facility:** University of Rochester **State:** New York **Zip:** 14642 **Location 114:** **City:** Stony Brook **Country:** United States **Facility:** Stony Brook University Medical Center **State:** New York **Zip:** 11794 **Location 115:** **City:** Syracuse **Country:** United States **Facility:** State University of New York Upstate Medical University **State:** New York **Zip:** 13210 **Location 116:** **City:** Valhalla **Country:** United States **Facility:** New York Medical College **State:** New York **Zip:** 10595 **Location 117:** **City:** Asheville **Country:** United States **Facility:** Mission Hospital Inc-Memorial Campus **State:** North Carolina **Zip:** 28801 **Location 118:** **City:** Chapel Hill **Country:** United States **Facility:** UNC Lineberger Comprehensive Cancer Center **State:** North Carolina **Zip:** 27599 **Location 119:** **City:** Charlotte **Country:** United States **Facility:** Carolinas Medical Center/Levine Cancer Institute **State:** North Carolina **Zip:** 28203 **Location 120:** **City:** Charlotte **Country:** United States **Facility:** Novant Health Presbyterian Medical Center **State:** North Carolina **Zip:** 28204 **Location 121:** **City:** Durham **Country:** United States **Facility:** Duke University Medical Center **State:** North Carolina **Zip:** 27710 **Location 122:** **City:** Winston-Salem **Country:** United States **Facility:** Wake Forest University Health Sciences **State:** North Carolina **Zip:** 27157 **Location 123:** **City:** Fargo **Country:** United States **Facility:** Sanford Broadway Medical Center **State:** North Dakota **Zip:** 58122 **Location 124:** **City:** Akron **Country:** United States **Facility:** Children's Hospital Medical Center of Akron **State:** Ohio **Zip:** 44308 **Location 125:** **City:** Cincinnati **Country:** United States **Facility:** Cincinnati Children's Hospital Medical Center **State:** Ohio **Zip:** 45229 **Location 126:** **City:** Cleveland **Country:** United States **Facility:** Rainbow Babies and Childrens Hospital **State:** Ohio **Zip:** 44106 **Location 127:** **City:** Cleveland **Country:** United States **Facility:** Cleveland Clinic Foundation **State:** Ohio **Zip:** 44195 **Location 128:** **City:** Columbus **Country:** United States **Facility:** Nationwide Children's Hospital **State:** Ohio **Zip:** 43205 **Location 129:** **City:** Dayton **Country:** United States **Facility:** Dayton Children's Hospital **State:** Ohio **Zip:** 45404 **Location 130:** **City:** Toledo **Country:** United States **Facility:** Mercy Children's Hospital **State:** Ohio **Zip:** 43608 **Location 131:** **City:** Youngstown **Country:** United States **Facility:** Tod Children's Hospital - Forum Health **State:** Ohio **Zip:** 44501 **Location 132:** **City:** Oklahoma City **Country:** United States **Facility:** University of Oklahoma Health Sciences Center **State:** Oklahoma **Zip:** 73104 **Location 133:** **City:** Portland **Country:** United States **Facility:** Legacy Emanuel Children's Hospital **State:** Oregon **Zip:** 97227 **Location 134:** **City:** Portland **Country:** United States **Facility:** Legacy Emanuel Hospital and Health Center **State:** Oregon **Zip:** 97227 **Location 135:** **City:** Portland **Country:** United States **Facility:** Oregon Health and Science University **State:** Oregon **Zip:** 97239 **Location 136:** **City:** Bethlehem **Country:** United States **Facility:** Lehigh Valley Hospital - Muhlenberg **State:** Pennsylvania **Zip:** 18017 **Location 137:** **City:** Danville **Country:** United States **Facility:** Geisinger Medical Center **State:** Pennsylvania **Zip:** 17822 **Location 138:** **City:** Hershey **Country:** United States **Facility:** Penn State Children's Hospital **State:** Pennsylvania **Zip:** 17033 **Location 139:** **City:** Philadelphia **Country:** United States **Facility:** Children's Hospital of Philadelphia **State:** Pennsylvania **Zip:** 19104 **Location 140:** **City:** Philadelphia **Country:** United States **Facility:** Saint Christopher's Hospital for Children **State:** Pennsylvania **Zip:** 19134 **Location 141:** **City:** Pittsburgh **Country:** United States **Facility:** Children's Hospital of Pittsburgh of UPMC **State:** Pennsylvania **Zip:** 15224 **Location 142:** **City:** Charleston **Country:** United States **Facility:** Medical University of South Carolina **State:** South Carolina **Zip:** 29425 **Location 143:** **City:** Columbia **Country:** United States **Facility:** Palmetto Health Richland **State:** South Carolina **Zip:** 29203 **Location 144:** **City:** Greenville **Country:** United States **Facility:** BI-LO Charities Children's Cancer Center **State:** South Carolina **Zip:** 29605 **Location 145:** **City:** Greenville **Country:** United States **Facility:** Greenville Cancer Treatment Center **State:** South Carolina **Zip:** 29605 **Location 146:** **City:** Sioux Falls **Country:** United States **Facility:** Sanford USD Medical Center - Sioux Falls **State:** South Dakota **Zip:** 57117-5134 **Location 147:** **City:** Chattanooga **Country:** United States **Facility:** T C Thompson Children's Hospital **State:** Tennessee **Zip:** 37403 **Location 148:** **City:** Johnson City **Country:** United States **Facility:** East Tennessee State University **State:** Tennessee **Zip:** 37614-0054 **Location 149:** **City:** Knoxville **Country:** United States **Facility:** East Tennessee Childrens Hospital **State:** Tennessee **Zip:** 37916 **Location 150:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt University/Ingram Cancer Center **State:** Tennessee **Zip:** 37232 **Location 151:** **City:** Amarillo **Country:** United States **Facility:** Texas Tech University Health Sciences Center-Amarillo **State:** Texas **Zip:** 79106 **Location 152:** **City:** Austin **Country:** United States **Facility:** Dell Children's Medical Center of Central Texas **State:** Texas **Zip:** 78723 **Location 153:** **City:** Corpus Christi **Country:** United States **Facility:** Driscoll Children's Hospital **State:** Texas **Zip:** 78411 **Location 154:** **City:** Dallas **Country:** United States **Facility:** Medical City Dallas Hospital **State:** Texas **Zip:** 75230 **Location 155:** **City:** Fort Sam Houston **Country:** United States **Facility:** Brooke Army Medical Center **State:** Texas **Zip:** 78234 **Location 156:** **City:** Fort Worth **Country:** United States **Facility:** Cook Children's Medical Center **State:** Texas **Zip:** 76104 **Location 157:** **City:** Houston **Country:** United States **Facility:** Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center **State:** Texas **Zip:** 77030 **Location 158:** **City:** Lubbock **Country:** United States **Facility:** Covenant Children's Hospital **State:** Texas **Zip:** 79410 **Location 159:** **City:** San Antonio **Country:** United States **Facility:** Methodist Children's Hospital of South Texas **State:** Texas **Zip:** 78229 **Location 160:** **City:** San Antonio **Country:** United States **Facility:** University of Texas Health Science Center at San Antonio **State:** Texas **Zip:** 78229 **Location 161:** **City:** Temple **Country:** United States **Facility:** Scott and White Memorial Hospital **State:** Texas **Zip:** 76508 **Location 162:** **City:** Salt Lake City **Country:** United States **Facility:** Primary Children's Hospital **State:** Utah **Zip:** 84113 **Location 163:** **City:** Burlington **Country:** United States **Facility:** University of Vermont College of Medicine **State:** Vermont **Zip:** 05405 **Location 164:** **City:** Falls Church **Country:** United States **Facility:** Inova Fairfax Hospital **State:** Virginia **Zip:** 22042 **Location 165:** **City:** Norfolk **Country:** United States **Facility:** Children's Hospital of The King's Daughters **State:** Virginia **Zip:** 23507 **Location 166:** **City:** Roanoke **Country:** United States **Facility:** Carilion Clinic Children's Hospital **State:** Virginia **Zip:** 24014 **Location 167:** **City:** Seattle **Country:** United States **Facility:** Seattle Children's Hospital **State:** Washington **Zip:** 98105 **Location 168:** **City:** Spokane **Country:** United States **Facility:** Providence Sacred Heart Medical Center and Children's Hospital **State:** Washington **Zip:** 99204 **Location 169:** **City:** Tacoma **Country:** United States **Facility:** Mary Bridge Children's Hospital and Health Center **State:** Washington **Zip:** 98405 **Location 170:** **City:** Tacoma **Country:** United States **Facility:** Madigan Army Medical Center **State:** Washington **Zip:** 98431 **Location 171:** **City:** Charleston **Country:** United States **Facility:** West Virginia University Charleston Division **State:** West Virginia **Zip:** 25304 **Location 172:** **City:** Green Bay **Country:** United States **Facility:** Saint Vincent Hospital Cancer Center Green Bay **State:** Wisconsin **Zip:** 54301 **Location 173:** **City:** Madison **Country:** United States **Facility:** University of Wisconsin Hospital and Clinics **State:** Wisconsin **Zip:** 53792 **Location 174:** **City:** Marshfield **Country:** United States **Facility:** Marshfield Clinic **State:** Wisconsin **Zip:** 54449 **Location 175:** **City:** Milwaukee **Country:** United States **Facility:** Children's Hospital of Wisconsin **State:** Wisconsin **Zip:** 53226 **Location 176:** **City:** North Adelaide **Country:** Australia **Facility:** Women's and Children's Hospital-Adelaide **State:** South Australia **Zip:** 5006 **Location 177:** **City:** Perth **Country:** Australia **Facility:** Princess Margaret Hospital for Children **State:** Western Australia **Zip:** 6008 **Location 178:** **City:** Edmonton **Country:** Canada **Facility:** University of Alberta Hospital **State:** Alberta **Zip:** T6G 2B7 **Location 179:** **City:** Vancouver **Country:** Canada **Facility:** British Columbia Children's Hospital **State:** British Columbia **Zip:** V6H 3V4 **Location 180:** **City:** Winnipeg **Country:** Canada **Facility:** CancerCare Manitoba **State:** Manitoba **Zip:** R3E 0V9 **Location 181:** **City:** Halifax **Country:** Canada **Facility:** IWK Health Centre **State:** Nova Scotia **Zip:** B3K 6R8 **Location 182:** **City:** Hamilton **Country:** Canada **Facility:** McMaster Children's Hospital at Hamilton Health Sciences **State:** Ontario **Zip:** L8N 3Z5 **Location 183:** **City:** Kingston **Country:** Canada **Facility:** Kingston Health Sciences Centre **State:** Ontario **Zip:** K7L 2V7 **Location 184:** **City:** Ottawa **Country:** Canada **Facility:** Children's Hospital of Eastern Ontario **State:** Ontario **Zip:** K1H 8L1 **Location 185:** **City:** Toronto **Country:** Canada **Facility:** Hospital for Sick Children **State:** Ontario **Zip:** M5G 1X8 **Location 186:** **City:** Montreal **Country:** Canada **Facility:** The Montreal Children's Hospital of the MUHC **State:** Quebec **Zip:** H3H 1P3 **Location 187:** **City:** Montreal **Country:** Canada **Facility:** Centre Hospitalier Universitaire Sainte-Justine **State:** Quebec **Zip:** H3T 1C5 **Location 188:** **City:** Regina **Country:** Canada **Facility:** Allan Blair Cancer Centre **State:** Saskatchewan **Zip:** S4T 7T1 **Location 189:** **City:** Saskatoon **Country:** Canada **Facility:** Saskatoon Cancer Centre **State:** Saskatchewan **Zip:** S7N 4H4 **Location 190:** **City:** Grafton **Country:** New Zealand **Facility:** Starship Children's Hospital **State:** Auckland **Zip:** 1145 **Location 191:** **City:** San Juan **Country:** Puerto Rico **Facility:** San Jorge Children's Hospital **Zip:** 00912 **Location 192:** **City:** Geneva **Country:** Switzerland **Facility:** Swiss Pediatric Oncology Group - Geneva **Zip:** 1205 #### Overall Officials **Official 1:** **Affiliation:** Children's Oncology Group **Name:** Nilsa Ramirez **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000006402 - Term: Hematologic Diseases - ID: D000007945 - Term: Leukemia, Lymphoid - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000015448 - Term: Leukemia, B-Cell - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000009196 - Term: Myeloproliferative Disorders - ID: D000001855 - Term: Bone Marrow Diseases - ID: D000054437 - Term: Myelodysplastic-Myeloproliferative Diseases - ID: D000015458 - Term: Leukemia, T-Cell - ID: D000034721 - Term: Mastocytosis, Systemic - ID: D000008415 - Term: Mastocytosis - ID: D000090362 - Term: Mast Cell Activation Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10955 - Name: Leukemia, Myeloid - Relevance: HIGH - As Found: Myeloid Leukemia - ID: M18127 - Name: Leukemia, Myeloid, Acute - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: M10951 - Name: Leukemia, Lymphoid - Relevance: LOW - As Found: Unknown - ID: M18116 - Name: Leukemia, Lymphocytic, Chronic, B-Cell - Relevance: HIGH - As Found: Chronic Lymphocytic Leukemia - ID: M18123 - Name: Leukemia, Myelogenous, Chronic, BCR-ABL Positive - Relevance: HIGH - As Found: Chronic Myelogenous Leukemia, BCR-ABL1 Positive - ID: M27585 - Name: Precursor Cell Lymphoblastic Leukemia-Lymphoma - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: M12307 - Name: Neoplasm Metastasis - Relevance: LOW - As Found: Unknown - ID: M18122 - Name: Leukemia, Prolymphocytic - Relevance: HIGH - As Found: Prolymphocytic Leukemia - ID: M27706 - Name: Leukemia, Myelomonocytic, Juvenile - Relevance: HIGH - As Found: Juvenile Myelomonocytic Leukemia - ID: M10950 - Name: Leukemia, Hairy Cell - Relevance: HIGH - As Found: Hairy cell leukemia - ID: M27552 - Name: Leukemia, Large Granular Lymphocytic - Relevance: HIGH - As Found: T-cell large granular lymphocyte leukemia - ID: M10952 - Name: Leukemia, Mast-Cell - Relevance: HIGH - As Found: Mast cell leukemia - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: M27708 - Name: Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - Relevance: HIGH - As Found: Atypical chronic myeloid leukemia - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - 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: M18115 - Name: Leukemia, B-Cell - 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: M12149 - Name: Myeloproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M5134 - Name: Bone Marrow Diseases - Relevance: LOW - As Found: Unknown - ID: M27707 - Name: Myelodysplastic-Myeloproliferative Diseases - Relevance: LOW - As Found: Unknown - ID: M18119 - Name: Leukemia, T-Cell - Relevance: LOW - As Found: Unknown - ID: M11399 - Name: Mastocytosis - Relevance: LOW - As Found: Unknown - ID: M24449 - Name: Mastocytosis, Systemic - Relevance: LOW - As Found: Unknown - ID: M2776 - Name: Mast Cell Activation Disorders - Relevance: LOW - As Found: Unknown - ID: T3995 - Name: Myeloid Leukemia - Relevance: HIGH - As Found: Myeloid Leukemia - ID: T182 - Name: Acute Myeloid Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: T188 - Name: Acute Non Lymphoblastic Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: T1308 - Name: Chronic Lymphocytic Leukemia - Relevance: HIGH - As Found: Chronic Lymphocytic Leukemia - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: HIGH - As Found: Chronic - ID: T1309 - Name: Chronic Myeloid Leukemia - Relevance: HIGH - As Found: Chronic Myeloid Leukemia - ID: T175 - Name: Acute Lymphoblastic Leukemia - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: T3533 - Name: Lymphoblastic Lymphoma - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T1134 - Name: Childhood Acute Lymphoblastic Leukemia - Relevance: HIGH - As Found: Childhood acute lymphoblastic leukemia - ID: T1310 - Name: Chronic Myelomonocytic Leukemia - Relevance: HIGH - As Found: Juvenile Myelomonocytic Leukemia - ID: T3174 - Name: Juvenile Myelomonocytic Leukemia - Relevance: HIGH - As Found: Juvenile Myelomonocytic Leukemia - ID: T2650 - Name: Hairy Cell Leukemia - Relevance: HIGH - As Found: Hairy cell leukemia - ID: T238 - Name: Aggressive NK Cell Leukemia - Relevance: HIGH - As Found: Large granular lymphocyte leukemia - ID: T5568 - Name: T-cell Large Granular Lymphocyte Leukemia - Relevance: HIGH - As Found: T-cell large granular lymphocyte leukemia - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown - ID: T1311 - Name: Chronic Myeloproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: T3994 - Name: Myelodysplastic/myeloproliferative Disease - Relevance: LOW - As Found: Unknown - ID: T3626 - Name: Mastocytosis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000009369 - Term: Neoplasms - ID: D000007951 - Term: Leukemia, Myeloid - ID: D000015470 - Term: Leukemia, Myeloid, Acute - ID: D000054198 - Term: Precursor Cell Lymphoblastic Leukemia-Lymphoma - ID: D000015451 - Term: Leukemia, Lymphocytic, Chronic, B-Cell - ID: D000015464 - Term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive - ID: D000007943 - Term: Leukemia, Hairy Cell - ID: D000015463 - Term: Leukemia, Prolymphocytic - ID: D000054438 - Term: Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - ID: D000054429 - Term: Leukemia, Myelomonocytic, Juvenile - ID: D000054066 - Term: Leukemia, Large Granular Lymphocytic - ID: D000007946 - Term: Leukemia, Mast-Cell ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01102179 **Brief Title:** Vitamin D Insufficiency and Deficiency in Chronic Kidney Disease (CKD) Patients in Singapore **Official Title:** Prevalence of Vitamin D Insufficiency and Deficiency in Chronic Kidney Disease Patients in Singapore #### Organization Study ID Info **ID:** DSRB Domain E/09/643 #### Organization **Class:** OTHER **Full Name:** National University of Singapore ### Status Module #### Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-11-07 **Type:** ESTIMATED **Last Update Submit Date:** 2014-11-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Start Date **Date:** 2010-04 **Status Verified Date:** 2014-10 #### Study First Post Date **Date:** 2010-04-13 **Type:** ESTIMATED **Study First Submit Date:** 2010-04-12 **Study First Submit QC Date:** 2010-04-12 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** National Kidney Foundation, Singapore #### Lead Sponsor **Class:** OTHER **Name:** National University of Singapore #### Responsible Party **Old Name Title:** Dr. Priscilla How **Old Organization:** National University Singapore/National University Hospital ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Vitamin D insufficiency and deficiency is common in chronic kidney disease (CKD) patients and is associated with elevated parathyroid hormone (PTH) concentration and mineral and bone disorder (MBD). There is also increasing evidence to show that these abnormalities increase cardiovascular morbidity and mortality in CKD patients. There is a need for early identification of vitamin D insufficiency/deficiency in CKD patients to prevent its long-term complications. However, the vitamin D status of CKD patients in Singapore has not been well described. The purpose of this study is to assess the vitamin D status of predialysis CKD patients in a tertiary academic teaching hospital in Singapore, and its association with parameters for MBD. Predialysis patients from the outpatient renal clinic at the National University Hospital (NUH) will be recruited into this study. Blood samples from the patients will be collected after an overnight fast to determine their serum 25(OH)D, creatinine, phosphorus, calcium, albumin and i-PTH concentrations. These parameters will be compared among patients in various stages of CKD. ### Conditions Module **Conditions:** - Stage 2-5 Chronic Kidney Disease - Predialysis ### Design Module #### Design Info **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 196 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All patients with stage 2-5 (pre-dialysis) chronic kidney disease One-time blood draw (10 ml) **Label:** Chronic kidney disease ### Outcomes Module #### Primary Outcomes **Description:** Vitamin D levels are only measured at one time point i.e. at baseline **Measure:** Vitamin D 25(OH)D levels **Time Frame:** baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female 21 years of age or older * CKD stage 2 to 5 (who are not on dialysis): CKD stage 2: eGFR 60-89ml/min/1.73m2, stage 3: eGFR 30-59ml/min/1.73m2, stage 4: eGFR 15-29 ml/min/1.73m2, stage 5 eGFR \<15 ml/min/1.73m2) * Not receiving over-the-counter or prescription vitamin D therapy * On a stable dose of phosphate binder (if any) for at least 1 month prior to the study Exclusion Criteria: * History of liver and chronic inflammatory diseases, primary hyperparathyroidism and malignancies * Use of corticosteroids, anticonvulsants or vitamin D compounds * Use of an investigational agent within 30 days of study entry **Minimum Age:** 21 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with stage 2-5 chronic kidney disease who are not on dialysis ### Contacts Locations Module #### Locations **Location 1:** **City:** Singapore **Country:** Singapore **Facility:** National University Hospital #### Overall Officials **Official 1:** **Affiliation:** National University of Singapore/National University Hospital **Name:** Priscilla P How, Pharm.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - 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: D000051437 - Term: Renal Insufficiency - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10698 - Name: Kidney Diseases - Relevance: HIGH - As Found: Kidney Disease - ID: M26717 - Name: Renal Insufficiency, Chronic - Relevance: HIGH - As Found: Chronic Kidney Disease - ID: M26718 - Name: Renal Insufficiency - 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: 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: D000007674 - Term: Kidney Diseases - ID: D000051436 - Term: Renal Insufficiency, Chronic ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: LOW - As Found: Unknown - ID: M6003 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01297179 **Brief Title:** A Study to Evaluate the Possible Effects of Taking Mirabegron While Taking a Contraceptive Pill **Official Title:** A Double-blind Two-sequence Crossover Study to Evaluate the Effect of Multiple Doses of YM178 on the Pharmacokinetics (PK) of an Ethinyl Estradiol and Levonorgestrel Containing Combined Oral Contraceptive (COC) #### Organization Study ID Info **ID:** 178-CL-068 #### Organization **Class:** INDUSTRY **Full Name:** Astellas Pharma Inc #### Secondary ID Infos **ID:** 2008-000216-32 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2009-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-07-03 **Type:** ESTIMATED **Last Update Submit Date:** 2013-07-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-03 **Type:** ACTUAL #### Start Date **Date:** 2008-10 **Status Verified Date:** 2011-02 #### Study First Post Date **Date:** 2011-02-16 **Type:** ESTIMATED **Study First Submit Date:** 2011-02-15 **Study First Submit QC Date:** 2011-02-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Astellas Pharma Inc #### Responsible Party **Old Name Title:** Disclosure Office Europe **Old Organization:** Astellas Pharma Europe BV ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The objective of this study is to determine the effect of multiple doses of mirabegron on the pharmacokinetics of an oral contraceptive. ### Conditions Module **Conditions:** - Healthy Volunteers - Pharmacokinetics of Mirabegron **Keywords:** - Pharmacokinetics - Oral contraceptives - Drug interactions - Pharmacokinetics of mirabegron ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Oral **Name:** Mirabegron **Other Names:** - YM178 **Type:** DRUG #### Intervention 2 **Description:** Oral **Name:** Minidril **Other Names:** - ethinyl estradiol - levonorgestrel **Type:** DRUG #### Intervention 3 **Description:** Oral **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Assessment of pharmacokinetics of Ethinyl estradiol (EE) and Levonorgestrel (LNG) by analysis of blood samples. **Time Frame:** Day 21 + Day 29 #### Secondary Outcomes **Measure:** Assessment of pharmacokinetics of mirabegron by analysis of blood samples. **Time Frame:** Day 21 + Day 49 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects above 35 years inclusive are re-evaluated for the risks of using of a COC * Body Mass Index between 18.5 and 30.0 kg/m2, inclusive * On oral contraceptive with 30ʯg ethinyl estradiol (EE) plus either 125ʯg or 150ʯg levonorgestrel (LNG) for at least three months prior to date of randomization and well tolerated * During the study the subject is willing to use 1 of the 3 following contraceptive methods: diaphragm with spermicide, intrauterine device or partner is using condoms in combination with a spermicidal cream Exclusion Criteria: Subjects will be excluded from participation if any of the following apply: * Known or suspected hypersensitivity to YM178 or any components of the formulation used * Pregnant or breast feeding within 6 months before screening assessment * Any of the liver function tests (i.e. ALT, AST and Alkaline phosphatase) above the upper limit of normal * Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active Hay-fever) * Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the medical investigator * Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests * Abnormal pulse and/or blood pressure measurements at the pre-study visit as follows: Pulse \<40 or \>90 bpm; mean systolic blood pressure \>140 mmHg; mean diastolic blood pressure \>90 mmHg (blood pressure measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically) * A marked baseline prolongation of QT/QTc interval after repeated measurements of \>450 ms, a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS) * Use of any prescribed or OTC (over-the-counter) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day) * Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit * Any use of drugs of abuse within 3 months prior to admission to the Clinical Unit * History of drinking more than 14 units of alcohol per week (1 unit = 270 cc of beer or 40 cc of spirits or 1 glass of wine) within 3 months prior to admission to the Clinical Unit * Positive test for drugs of abuse or positive alcohol test on the day of admission into the clinical unit * History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the Clinical Unit * Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study * Donation of blood or blood products within 3 months prior to admission to the Clinical Unit * Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2 * Subjects who, in the opinion of the investigator, are not likely to complete the trial for any reason * Unwillingness to use additional barrier contraceptive methods for the course of the study and for one month after the end of study visit * Any clinical condition, which, in the opinion of the investigator would not allow safe completion of the study **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Paris **Country:** France **Zip:** 75015 #### Overall Officials **Official 1:** **Affiliation:** Astellas Pharma Europe B.V. **Name:** Use Central Contact **Role:** STUDY_DIRECTOR ### References Module #### See Also Links **Label:** Link to Results on JAPIC **URL:** http://www.clinicaltrials.jp/user/ctrDetail_e.jsp?resultId=640 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000004967 - Term: Estrogens - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000080066 - Term: Contraceptive Agents, Hormonal - ID: D000003270 - Term: Contraceptive Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000003271 - Term: Contraceptive Agents, Female - ID: D000003280 - Term: Contraceptives, Oral, Synthetic - ID: D000003276 - Term: Contraceptives, Oral - ID: D000003278 - Term: Contraceptives, Oral, Hormonal - ID: D000058667 - Term: Adrenergic beta-3 Receptor Agonists - ID: D000000318 - Term: Adrenergic beta-Agonists - ID: D000000322 - Term: Adrenergic Agonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000064804 - Term: Urological Agents ### Intervention Browse Module - Browse Branches - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Urol - Name: Urological Agents ### Intervention Browse Module - Browse Leaves - ID: M8145 - Name: Ethinyl Estradiol - Relevance: HIGH - As Found: Iodine - ID: M266279 - Name: Estradiol 17 beta-cypionate - Relevance: LOW - As Found: Unknown - ID: M266280 - Name: Estradiol 3-benzoate - Relevance: LOW - As Found: Unknown - ID: M8108 - Name: Estradiol - Relevance: HIGH - As Found: Cell lymphoma - ID: M234941 - Name: Polyestradiol phosphate - Relevance: LOW - As Found: Unknown - ID: M19256 - Name: Levonorgestrel - Relevance: HIGH - As Found: SBRT - ID: M6494 - Name: Contraceptive Agents - Relevance: LOW - As Found: Unknown - ID: M244406 - Name: Mirabegron - Relevance: HIGH - As Found: Acne - ID: M6500 - Name: Contraceptives, Oral - Relevance: LOW - As Found: Unknown - ID: M6501 - Name: Contraceptives, Oral, Combined - Relevance: LOW - As Found: Unknown - ID: M8116 - Name: Estrogens - 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: M2116 - Name: Contraceptive Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M6495 - Name: Contraceptive Agents, Female - Relevance: LOW - As Found: Unknown - ID: M6502 - Name: Contraceptives, Oral, Hormonal - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M29193 - Name: Adrenergic beta-3 Receptor Agonists - Relevance: LOW - As Found: Unknown - ID: M3670 - Name: Adrenergic beta-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: D000016912 - Term: Levonorgestrel - ID: D000004997 - Term: Ethinyl Estradiol - ID: C000520025 - Term: Mirabegron - ID: D000004958 - Term: Estradiol ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04944979 **Acronym:** KIDCARES10 **Brief Title:** Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10) **Official Title:** A Phase III, Open-label, Prospective, Multicenter Study to Assess Efficacy, Safety, and Pharmacokinetics of Kedrion Intravenous Human Normal Immunoglobulin (IVIg) 10% in Pediatric Patients Affected by Primary Immunodeficiency Disease (PID) #### Organization Study ID Info **ID:** KB070 #### Organization **Class:** INDUSTRY **Full Name:** Kedrion S.p.A. ### Status Module #### Completion Date **Date:** 2026-10-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-23 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-04-30 **Type:** ESTIMATED #### Start Date **Date:** 2021-03-31 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2021-06-30 **Type:** ACTUAL **Study First Submit Date:** 2021-06-11 **Study First Submit QC Date:** 2021-06-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Kedrion S.p.A. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to assess efficacy, safety and pharmacokinetics of Kedrion Immunoglobulin 10% (KIg10) in pediatric patients with Primary Immunodeficiency Disease (PID). ### Conditions Module **Conditions:** - Primary Immunodeficiency Disease **Keywords:** - Immunoglobulin - Kedrion IVIG 10% - IgG Antibodies - Agammaglobulinemia - Hypogammaglobulinemia - Pediatric ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive intravenous infusion of Kedrion IVIG 10% at a dose of 200 to 800 milligram per kilogram (mg/kg) body weight every 21 or 28 days for period of 48 weeks. **Intervention Names:** - Biological: Kedrion IVIG 10% **Label:** Experimental: Kedrion IVIG 10% **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental: Kedrion IVIG 10% **Description:** Kedrion intravenous immunoglobulin (IVIg) 10% **Name:** Kedrion IVIG 10% **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Incidence rate (i.e., the mean number of acute serious bacterial infections per patientyear) of acute serious bacterial infections (bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis) according to pre-specified criteria). **Measure:** Incidence Rate of Acute Serious Bacterial Infections **Time Frame:** From Baseline (Day 1) up to week 51/52 #### Secondary Outcomes **Measure:** Serum Immunoglobulin G (IgG) trough levels **Time Frame:** Before each infusion of KIg10 and at the study termination visit (Week 51/52) **Measure:** Immunoglobulin G (IgG) subclasses levels (IgG1, IgG2, IgG3, IgG4) **Time Frame:** Before infusions 1, 5, 9 and 13 for the 28-day infusion schedule, and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule **Measure:** Frequency of patients with total Immunoglobulin G (IgG) below 6 g/L **Time Frame:** Day 1 up to week 51/52 **Description:** The quantitative evaluation will be reported **Measure:** Anti-tetanus toxoid antibody level **Time Frame:** Before infusions 1, 5, 9 and 13 for the 28-day infusion schedule and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule **Description:** The quantitative evaluation will be reported **Measure:** Anti-pneumococcal capsular polysaccharide antibody level **Time Frame:** Before infusions 1, 5, 9 and 13 for the 28-day infusion schedule and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule **Description:** The quantitative evaluation will be reported **Measure:** Anti-measles antibody level **Time Frame:** Before infusions 1, 5, 9 and 13 for the 28-day infusion schedule and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule **Description:** The quantitative evaluation will be reported **Measure:** Anti-Haemophilus influenza type b antibody level **Time Frame:** Before infusions 1, 5, 9 and 13 for the 28-day infusion schedule and before infusions 1, 7, 11 and 17 for the 21-day infusion schedule **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Incidence rate (i.e., the mean number per patient-year) of any infection other than acute serious bacterial infections **Time Frame:** From day 1 to week 51/52 **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Duration of any infection other than acute serious bacterial infections **Time Frame:** From day 1 to week 51/52 **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Incidence rate (i.e. the mean number per patient-year) of fever episodes **Time Frame:** From day 1 to week 51/52 **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Duration of fever episodes **Time Frame:** From day 1 to week 51/52 **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Overall hospitalization days **Time Frame:** From day 1 to week 51/52 **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Days of hospitalizations due to infection **Time Frame:** From day 1 to week 51/52 **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Incidence rate (i.e. the mean number per patient-year) of patient on antibiotics for the treatment of any kind of infection **Time Frame:** From day 1 to week 51/52 **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Duration of patients on antibiotics for the treatment of any kind of infection **Time Frame:** From day 1 to week 51/52 **Description:** Information reported by participant/participant's parent(s)/legal guardian(s) in the Patient Diary, provided starting from the first infusion. **Measure:** Days of missed work/school/other major activities due to infections **Time Frame:** From day 1 to week 51/52 **Description:** The PedsQL™ Measurement Model is a modular approach to measuring health-related QoL in healthy children and adolescents and those with acute and chronic health conditions. The 23-item PedsQL™ Generic Core Scales were designed to measure the core dimension of health as delineated by the World Health Organization, as well as role (school) functioning. The total scale score (23 items) consists of Physical health summary score (8 items) and Psychosocial health summary score (15 items). Physical health summary includes Physical Functioning (8 items) and Psychosocial health summary score includes Emotional Functioning (5 items), Social Functioning (5 items) and School Functioning (5 items). The overall range for PedsQL scores is 0 to 100, with a higher score indicating better quality of life. **Measure:** Pediatric Quality of Life Inventory (Pedsql) Score **Time Frame:** At baseline, week 24, and study termination visit **Measure:** Number of Adverse Events (%) and proportion of patients experiencing at least one Adverse Event (AE) **Time Frame:** From Baseline (Day 1) up to Week 51/52 **Measure:** Number of Serisous AEs (%) and proportion of patients experiencing at least one Serious Adverse Event (SAE) **Time Frame:** From Baseline (Day 1) up to Week 51/52 **Measure:** Number of related infusion AEs (%) occurring during infusion or within 1, 24, and 72 hours after the end of infusion, and proportion of patients experiencing at least one related infusion AE. at least 1 of such related infusion AE. **Time Frame:** From Baseline (Day 1) up to Week 51/52 **Measure:** The proportion and number of KIg10 infusions for which the infusion rate is decreased due to Adverse Events. **Time Frame:** From Baseline (Day 1) up to Week 51/52 **Measure:** Number and proportion of infusions with one or more infusion (temporally-associated) Adverse Event. **Time Frame:** From Baseline (Day 1) up to Week 51/52 **Description:** Number of participants with changes from baseline in vital signs (including blood pressure, heart rate and temperature); Physical examination (including evaluation of all body systems, body weight, height and Tanner Staging); Safety Laboratory Tests (including hematology, serum chemistry, and urinalysis) will be reported. **Measure:** Number of Participants with Changes from Baseline Values in Vital Signs, Physical Examinations, Safety Laboratory Tests (hematology, serum chemistry and urinalysis). **Time Frame:** Up to Week 51/52 **Measure:** The proportion and number of patients with a positive Coomb's test **Time Frame:** Following infusion 7 for the 28-day infusion schedule and infusion 9 for the 21-day infusion schedule **Measure:** The proportion and number of patients with a positive urine hemosiderin test **Time Frame:** Following infusion 7 for the 28-day infusion schedule and infusion 9 for the 21- day infusion schedule **Measure:** Serum haptoglobin level **Time Frame:** Following infusion 7 for the 28-day infusion schedule and infusion 9 for the 21-day infusion schedule. **Measure:** Serum Total Immunoglobulin G (IgG) levels, IgG Subclasses Levels, and Selected Specific Antibody Levels **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Plasma Concentration - Time Curve Of Total Immunoglobulin G (IgG) **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Elimination Half-Life (t1/2) of Total Immunoglobulin G (IgG) **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Total Immunoglobulin G (IgG) **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC[0-inf]) of Total Immunoglobulin G (IgG) **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Volume of Distribution of Total Immunoglobulin G (IgG) **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Maximum Observed Plasma Concentration (Cmax) Of Total IgG **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Time to Reach the Maximum Plasma Concentration (Tmax) of Total Immunoglobulin G (IgG) **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Elimination Rate Constant of Total Immunoglobulin G (IgG) **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-Tau) of Total Immunoglobulin G (IgG) **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Description:** The quantitative evaluation of the anti-Tetanus toxoid, anti-pneumococcal capsular polysaccharide, anti-Haemophilus influenza type B and anti-measles antibodies level will be reported **Measure:** Plasma Concentration-Time Curve Of Specific Immunoglobulin G (IgG) Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Elimination Half-Life (t1/2) of Specific IgG Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Specific Immunoglobulin G (IgG) Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Volume Of Distribution of Specific Immunoglobulin G (IgG) Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Maximum Observed Plasma Concentration (Cmax) of Specific Immunoglobulin G (IgG) Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Time to Reach the Maximum Plasma Concentration (Tmax) of Specific Immunoglobulin G (IgG) Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Elimination Rate Constant of Specific Immunoglobulin G (IgG) Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Specific Immunoglobulin G (IgG) Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) **Measure:** Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-Tau) of Specific Immunoglobulin G (IgG) Antibodies **Time Frame:** Before and after infusion 5 (28-day infusion schedule) or infusion 7 (21-day infusion schedule) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Written informed consent/assent obtained from the patient and his/her parent(s) or legally acceptable representative indicating that they understand the purpose of and procedures required for the study and are willing to participate in it. 2. Confirmed clinical diagnosis of a PID as defined by 2017 International Union of Immunological Societies (IUIS) Phenotypic Classification for Primary Immunodeficiencies (Bousfiha A, 2018 - and subsequent revisions) and The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity (Seidel MG et al., 2019 - and subsequent revisions) and requiring treatment with IVIg. Documented agammaglobulinemia (defined as the total absence of one or more classes of antibodies) or hypogammaglobulinemia (defined as low levels of one or more classes \[i.e., at least 2 standard deviations under the mean level per age\]). (NOTE: IVIg treatment is generally requested in the absence of IgG independently from whether other antibodies are absent). 3. Male or female, age from 2 up to \< 16 years, at the time of screening. 4. Received 200 to 800 mg/kg of a commercially available IVIg therapy in the range of 21- or 28-day intervals (±3 or ±4 days, respectively) for at least 3 infusions prior to screening. (NOTE: Other IVIgs will be prohibited after ICF signature and until study end, week 51/52). 5. At least 2 documented IgG trough levels while receiving an IVIg, of ≥ 6 g/L obtained at 2 infusions within 12 months (1 must be within 6 months) prior to ICF signature. 6. Patient and his/her parent(s)/legal guardian(s) are willing to comply with all requirements of the protocol. 7. Females of child-bearing potential with a negative pregnancy test (serum or urine) and who agree to employ adequate birth control measures during the study, such as: 1. sexual abstinence, to be evaluated in relation to the preferred and usual lifestyle of the subject; 2. male or female condom with or without spermicide; 3. cap, diaphragm or sponge with spermicide; 4. progestogen-only oral hormonal contraception, if already used in the past on medical prescription. Adequate birth control measures should be maintained throughout the study under parental control. 8. Authorization to access personal health information. 9. Patients previously participating in a clinical trial with another experimental IVIg may be enrolled if they have received stable commercially available IVIg therapy for at least 3 infusions (21 or 28 days) prior to screening. 10. Patients currently on treatment with any subcutaneous immunoglobulin (SCIG) can be enrolled if they are switched to stable commercially available IVIg therapy for at least 3 infusions (21 or 28 days) prior to screening. 11. Males or females with a body weight greater than or equal to 15 kg (≥ 15 kg). Exclusion Criteria: 1. Newly diagnosed PID and naïve to IgG replacement therapy. 2. Dysgammaglobulinemia (defined as a deficiency in one or more classes of antibodies, but not severe enough to require substitutive therapy) or isolated IgG subclass deficiency, or profound primary T cell deficiency (defined as the absence or severe reduction of T lymphocytes \[CD3+ \< 300 cell/mm3\] and an absent or particularly low proliferative response \[10% of the lower normal range\] to phytohaemagglutinin P \[PHA\]). 3. History of severe or serious reactions or hypersensitivity to IVIg or other injectable forms of IgG. 4. History of thrombotic events including deep vein thrombosis, cerebrovascular accident, pulmonary embolism, transient ischemic attacks, or myocardial infarction, as defined by at least 1 event in patient's lifetime. 5. IgA deficiency with documented antibodies to IgA. 6. Received blood products that have not undergone viral inactivation measures within 12 months prior to ICF signature. 7. Significant protein losing enteropathy, nephrotic syndrome, or lymphangiectasia. 8. An acute infection as documented by culture or diagnostic imaging and/or a body temperature ≥38.5 °C (≥101.3 °F) within 7 days prior to screening. 9. Acquired immunodeficiency syndrome (AIDS) and/or hepatitis B/C active disease at ICF signature. 10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times of the upper limit of normal for the laboratory designated for the study. 11. Using an implanted venous access device. 12. Moderate or severe anemia, defined according to patient's age as shown in the following table (World Health Organization, 2011) or persistent severe neutropenia (≤ 500 neutrophils per mm3) or persistent lymphopenia of less than 500 cells per microliter. 13. A severe chronic condition such as renal failure \[defined as abnormalities in kidney structure or function that are present for more than 3 months and have health implications. The disease is classified on the basis of cause and category of glomerular filtration rate (GFR) (G1 to G5) and albuminuria (A1 to A3) (KIDIGO, 2017). See the following table\], congestive heart failure (New York Heart Association III/IV), cardiomyopathy, cardiac arrhythmia associated with thromboembolic events (e.g., atrial fibrillation), unstable or advanced ischemic heart disease, hyperviscosity, or any other condition that the Investigator believes is likely to interfere with evaluation of the study drug or with satisfactory conduct of the trial. 14. History of a malignant disease other than properly treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin within 24 months prior to ICF signature. 15. History of pharmacoresistant epilepsy or multiple episodes of migraine (defined as at least 1 episode within 6 months of ICF signature) not controlled by medication. 16. Patient must not be receiving the following medication from at least 30 days prior to ICF signature: 1. Steroids, inhaled, oral or parenteral, at a daily dosage of ≥ 0.15 mg/kg/day of prednisone or equivalent). 2. Other immunosuppressive drugs (including monoclonal antibodies) or chemotherapy. 17. Females who are pregnant, breast feeding or planning a pregnancy during the course of the study. Women who become pregnant during the study will be withdrawn from the study. 18. Participated in another clinical study within 30 days prior to ICF signature. 19. Active drug or alcohol abuse or history of drug or alcohol abuse within the 6 months before screening. 20. Direct relative of an employee of the CRO, the study site, or Kedrion. 21. Previously treated under this protocol. 22. Unable to provide informed consent. 23. Patients with any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives or the patient's participation in this trial. 24. Patients with Hypersensitivity to the active substance or to any of the excipients. **Maximum Age:** 16 Years **Minimum Age:** 2 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Nicola Rovai **Phone:** +39 335 6524750 **Role:** CONTACT #### Locations **Location 1:** **City:** Chula Vista **Contacts:** ***Contact 1:*** - **Name:** Jibran Atwi - **Role:** CONTACT ***Contact 2:*** - **Name:** Jibran Atwi - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Velocity Clinical Research - MedPharmics - Lafayette **State:** California **Status:** NOT_YET_RECRUITING **Zip:** 91911 **Location 2:** **City:** San Francisco **Contacts:** ***Contact 1:*** - **Name:** Kathy Nguyen - **Role:** CONTACT ***Contact 2:*** - **Name:** Morna Dorsey - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Benioff Children's Hospital - Mission Bay **State:** California **Status:** NOT_YET_RECRUITING **Zip:** 94158 **Location 3:** **City:** Centennial **Contacts:** ***Contact 1:*** - **Name:** Maureen Collins - **Role:** CONTACT ***Contact 2:*** - **Name:** Isaac Melamed - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** IMMUNOe Health and Research Centers **State:** Colorado **Status:** NOT_YET_RECRUITING **Zip:** 80112 **Location 4:** **City:** Shreveport **Contacts:** ***Contact 1:*** - **Name:** Tracy Norwood - **Role:** CONTACT ***Contact 2:*** - **Name:** Juanita Valdes Camacho - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Louisiana State University Shreveport **State:** Louisiana **Status:** NOT_YET_RECRUITING **Zip:** 71103 **Location 5:** **City:** Las Vegas **Contacts:** ***Contact 1:*** - **Name:** Chanelle Lochan - **Role:** CONTACT ***Contact 2:*** - **Name:** Waseem Alhushki - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Alliance for Childhood Diseases dba Cure 4 The Kids Foundation **State:** Nevada **Status:** NOT_YET_RECRUITING **Zip:** 89135 **Location 6:** **City:** Toledo **Contacts:** ***Contact 1:*** - **Name:** Saima Faisal - **Role:** CONTACT ***Contact 2:*** - **Name:** Syed Rehman - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Asthma and Allergy Center - Toledo **State:** Ohio **Status:** NOT_YET_RECRUITING **Zip:** 43617 **Location 7:** **City:** Tulsa **Contacts:** ***Contact 1:*** - **Name:** Beverly Solis - **Role:** CONTACT ***Contact 2:*** - **Name:** Iftikhar Hussain - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Allergy, Asthma & Immunology Central/Vital Prospects Clinical Research Institute PC **State:** Oklahoma **Status:** NOT_YET_RECRUITING **Zip:** 74136 **Location 8:** **City:** Budapest **Country:** Hungary **Facility:** Dél-Pesti Centrumkórház - Országos Hematológiai És Infektológiai Intézet **Status:** ACTIVE_NOT_RECRUITING **Location 9:** **City:** Brescia **Country:** Italy **Facility:** SST Spedali Civili di Brescia **Status:** ACTIVE_NOT_RECRUITING **Location 10:** **City:** Firenze **Contacts:** ***Contact 1:*** - **Name:** Chiara Azzari - **Role:** CONTACT ***Contact 2:*** - **Name:** Clementina Canessa - **Role:** SUB_INVESTIGATOR ***Contact 3:*** - **Name:** Chiara Azzari - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Italy **Facility:** Azienda Ospedaliero-Universitaria - Ospedale Pediatrico Meyer **Status:** RECRUITING **Location 11:** **City:** Genova **Country:** Italy **Facility:** I.R.C.C.S. Istituto Giannina Gaslini **Status:** ACTIVE_NOT_RECRUITING **Location 12:** **City:** Milano **Country:** Italy **Facility:** Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinic **Status:** ACTIVE_NOT_RECRUITING **Location 13:** **City:** Napoli **Country:** Italy **Facility:** Azienda Ospedaliera Universitaria "Federico II" **Status:** ACTIVE_NOT_RECRUITING **Location 14:** **City:** Roma **Country:** Italy **Facility:** Fondazione Policlinico Tor Vergata **Status:** ACTIVE_NOT_RECRUITING **Location 15:** **City:** Roma **Country:** Italy **Facility:** IRCCS Ospedale Pediatrico Bambino Gesù **Status:** ACTIVE_NOT_RECRUITING **Location 16:** **City:** Lisbon **Country:** Portugal **Facility:** Centro Hospitalar Lisboa Central - Hospital Dona Estefânia **Status:** ACTIVE_NOT_RECRUITING **Location 17:** **City:** Porto **Country:** Portugal **Facility:** Centro Hospitalar Universitário do Porto - Hospital Santo António **Status:** ACTIVE_NOT_RECRUITING **Location 18:** **City:** Moscow **Country:** Russian Federation **Facility:** Children's City Clinical Hospital No. 9 named after G.N. Speransky, Moscow City Health Department **Status:** ACTIVE_NOT_RECRUITING **Location 19:** **City:** Moscow **Country:** Russian Federation **Facility:** Dmitry Rogachev National Medical Research Center for Pediatric Hematology, Oncology and Immunology **Status:** ACTIVE_NOT_RECRUITING **Location 20:** **City:** Bratislava **Country:** Slovakia **Facility:** Národný ústav detských chorôb (National Institute of Pediatric Diseases) **Status:** ACTIVE_NOT_RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Azienda Ospedaliero-Universitaria Ospedale Pediatrico Meyer - Italy **Name:** Chiara Azzari **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007154 - Term: Immune System Diseases - ID: D000030342 - Term: Genetic Diseases, Inborn ### Condition Browse Module - Browse Branches - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10199 - Name: Immunologic Deficiency Syndromes - Relevance: HIGH - As Found: Immunodeficiency Diseases - ID: M2285 - Name: Primary Immunodeficiency Diseases - Relevance: HIGH - As Found: Primary Immunodeficiency Diseases - ID: M3711 - Name: Agammaglobulinemia - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000081207 - Term: Primary Immunodeficiency Diseases - ID: D000007153 - Term: Immunologic Deficiency Syndromes ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M10122 - Name: Immunoglobulin G - Relevance: LOW - As Found: Unknown - ID: M19117 - Name: Immunoglobulins, Intravenous - Relevance: LOW - As Found: Unknown - ID: M8836 - Name: gamma-Globulins - Relevance: LOW - As Found: Unknown - ID: M20191 - Name: Rho(D) Immune Globulin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00944879 **Acronym:** CATSA **Brief Title:** Preparing for Adolescent HIV Vaccine Trials in South Africa: **Official Title:** Preparing for Adolescent HIV Vaccine Trials in South Africa: a Multi-centre Study to Evaluate Acceptability of the HPV Vaccine in Adolescents #### Organization Study ID Info **ID:** 35384 #### Organization **Class:** OTHER **Full Name:** Desmond Tutu HIV Centre #### Secondary ID Infos **ID:** CT.2006.33111.004 ### Status Module #### Completion Date **Date:** 2011-02 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2009-08-17 **Type:** ESTIMATED **Last Update Submit Date:** 2009-08-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2011-02 **Type:** ESTIMATED #### Start Date **Date:** 2009-08 **Status Verified Date:** 2009-07 #### Study First Post Date **Date:** 2009-07-23 **Type:** ESTIMATED **Study First Submit Date:** 2009-07-20 **Study First Submit QC Date:** 2009-07-22 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** European and Developing Countries Clinical Trials Partnership (EDCTP) **Class:** INDUSTRY **Name:** Merck Sharp & Dohme LLC #### Lead Sponsor **Class:** OTHER **Name:** Desmond Tutu HIV Centre #### Responsible Party **Old Name Title:** Professor Linda-Gail Bekker **Old Organization:** Desmond Tutu HIV Centre ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study will use the licensed HPV vaccine, Gardasil, as a surrogate for an HIV vaccine, in order to explore some of the ethico-legal,psycho-social and logistical challenges involved in running an HIV vaccine trial in adolescents. **Detailed Description:** This study will use the licensed HPV vaccine, an alternative STI vaccine, as a proxy for an HIV vaccine and thereby identify potential challenges to the inclusion of adolescents in HIV prevention trials. The study will allow for site capacity building in terms of recruiting and retaining an HIV-negative high-risk adolescent cohort, and assessing the acceptability of an STI vaccine to adolescents and their parents or guardians. Correlates of vaccine uptake, refusal, retention and attrition will be determined. In addition, the study will document the incidence of HIV, other sexually transmitted infections (STI's) and pregnancies and circumcisions in this age group. Different methods of assessing understanding in adolescents will be tested, to ensure that informed consent is being achieved. Experiences of privacy and confidentiality issues for adolescents in such research will be explored. Finally, psycho-social correlates of sexual risk and protective behaviour will be examined. The study is designed as a longitudinal cohort study with a self-selected intervention and control group. Adolescents and parents will be recruited through community outreach and invited to attend a Vaccine Discussion Group (VDG) to learn more about the HPV vaccine. Parental/ legal guardian consent and adolescent assent will be obtained prior to screening. After screening to ensure volunteers meet inclusion criteria, 1400 participants will be enrolled across seven sites. At this point, they will decide whether or not they want to receive the HPV vaccine. Those who do will receive three doses, at 0, 2 and 6 months. All participants will undergo HIV and pregnancy testing, receive risk reduction counseling and complete questionnaires at 0, 2, 6 and 9 months. Recruitment and retention will be monitored and data as described above will be collected throughout the course of the study. ### Conditions Module **Conditions:** - HIV Infection - HIV Infections **Keywords:** - HIV - vaccine - prevention - HPV - adolescents ### Design Module #### Bio Spec **Description:** Blood for HIV, syphilis and pregnancy testing **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1400 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Those choosing to receive the HPV vaccine **Label:** HPV vaccine #### Arm Group 2 **Description:** Those choosing not to receive the HPV vaccine **Label:** no HPV vaccine ### Outcomes Module #### Primary Outcomes **Measure:** Recruitment and retention **Time Frame:** 9 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Youth age 12-17 years * For 12-15 year olds - no sexual risk criteria * For 16-17 year olds (the age of lawful consent to sex in South Africa): sexually active (ever had sexual intercourse) * Willing to participate in HIV testing and counseling * Willing and able to assent to study * Parent or legal guardian willing to provide written consent * HIV-negative serostatus at screening and enrolment * Females must have a negative pregnancy test at screening/enrolment * Females must not be breastfeeding * Additional inclusion criteria for those accepting HPV vaccination: * No HPV immunizations * Females should agree to avoid pregnancy through to the end of the study and to take contraceptives throughout the study (access provided) Exclusion Criteria: * Exclusion criteria for those accepting HPV vaccination: * Presence of any serious illness requiring treatment with systemic medications, excluding short course oral steroids or inhaled steroid treatment for asthma * Contra-indication to vaccination, such as bleeding disorder * Previous allergic reaction to any vaccines or to constituents of these vaccines (yeast, thimerosal or aluminum) * Current immunomodulator therapy * Receipt of immunosuppressor therapy (more than 10mg/day of prednisone or equivalent for \>1 week) in the 6 months preceding enrollment date * Receipt of any vaccine within two weeks preceding enrollment date **Healthy Volunteers:** True **Maximum Age:** 17 Years **Minimum Age:** 12 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** South African adolescents aged 12 to 17 ### Contacts Locations Module #### Locations **Location 1:** **City:** Cape Town **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Melissa L Wallace, MSc, PhD - **Phone:** +27 21 650 6960 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Agnes Ronan, RGN, MBA - **Phone:** +27 21 650 6962 - **Role:** CONTACT ***Contact 3:*** - **Name:** Linda-Gail Bekker, MBChB, PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** South Africa **Facility:** Desmond Tutu HIV Centre #### Overall Officials **Official 1:** **Affiliation:** Desmond Tutu HIV Centre **Name:** Linda-Gail Bekker, MBChB PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000086982 - Term: Blood-Borne 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: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: HIGH - As Found: HIV Infections - ID: M18250 - Name: HIV Infections - Relevance: HIGH - As Found: HIV Infections - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M10199 - Name: Immunologic Deficiency Syndromes - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - 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: 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: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000015658 - Term: HIV Infections - ID: D000000163 - Term: Acquired Immunodeficiency Syndrome ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00211679 **Brief Title:** Intra-articularInjection of Botulinum Toxin Type **Official Title:** Intra-articularInjection of Botulinum Toxin Type a for the Treatment of Chronic Knee Pain: A Randomized, Placebo Controlled, Double Blind Study #### Organization Study ID Info **ID:** Protocol Number 03393B #### Organization **Class:** FED **Full Name:** Minneapolis Veterans Affairs Medical Center ### Status Module #### Completion Date **Date:** 2007-06 **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2005-09-21 **Type:** ESTIMATED **Last Update Submit Date:** 2005-09-13 **Overall Status:** UNKNOWN #### Start Date **Date:** 2004-06 **Status Verified Date:** 2005-07 #### Study First Post Date **Date:** 2005-09-21 **Type:** ESTIMATED **Study First Submit Date:** 2005-09-13 **Study First Submit QC Date:** 2005-09-13 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Allergan **Class:** OTHER **Name:** Center for Veterans Research and Education #### Lead Sponsor **Class:** FED **Name:** Minneapolis Veterans Affairs Medical Center ### Description Module **Brief Summary:** The purpose of this study is to determine whether intra-articular injection of botulinum toxin is effective in the treatment of chronic knee paindue to arthritis. **Detailed Description:** Chronic knee pain unresponsive to oral medications and intra-articular corticosteroids and viscosupplements is an important treatment problem, especially for the young, very old and those with complex medical problems that preclude joint reconstructive surgery. We hypothesized that intra-articular botulinum toxin could provide important joint pain relief in these patients. This is a prospective, double blined, placebo controlled 6month trial with an open label extension phase when pain returns to baseline levels (re-injection with 100units of botulinum toxin and 6 months followup thereafter. Comparisons: Intra-articular injection of bootulinum toxin type a will be compared to intra-articular injection of lidocaine the saline. ### Conditions Module **Conditions:** - Arthritis - Pain **Keywords:** - Joint pain - Knee Pain - Arthritis - Intra-articular Botulinum Toxin Type A ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Botulinum Toxin Type A **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Change in Pain Score **Measure:** Change in Joint Function **Measure:** Patient Global Assessment #### Secondary Outcomes **Measure:** Pain Relief **Measure:** Change in Health Status Quality of Life-SF36 **Measure:** Change in Disease specific Health Related QOL-WOMAC **Measure:** Function improvement by Timed Stands Test and Range of Motion **Measure:** Physican Assessment of Pain and Global Assessment of Improvement **Measure:** Safety Measure, ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female subjects, 18 years of age or older. * Written informed consent and written authorization for use or release of health and research study information have been obtained. * Subject has chronic Knee pain for more than 1 year. * Subject has pain \>4.5 on numerical rating scale of 0 to 10. * Ability to follow study instructions and likely to complete all required visits. * Negative urine pregnancy test on the day of treatment prior to the administration of study medication (for females of childbearing potential if applicable) * Patients previously treated with intra-articular corticosteroid or viscosupplementation injections. * Patients with rheumatoid arthritis must have failed therapy with standard DMARDs (disease modifying anti-rheumatic drugs) and anti-TNF agents unless they have a contraindication to TNF blockers. * Patients who were considered not to be candidates for Knee joint replacement because of young age, abnormalities in periarticular tissues or because of co-morbid conditions. * Must be ambulatory and able to perform sit to stand. Exclusion Criteria: * Use of aminoglycoside antibiotics, curare-like agents, or other agents that might interfere with neuromuscular function. * Any medical condition that may put the subject at increased risk with exposure to botulinum neurotoxin including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amytrophic lateral sclerosis, any other disorder that might interfere with neuromuscular function or the presence of severe peripheral neuropathy. * Females who are pregnant, breast-feeding, or planning a pregnancy during the study or who think that they may be pregnant at the start of the study, or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study. * Known allergy or sensitivity to any of the components in the study medication. * Evidence of recent alcohol or drug abuse. * Infection at injection site or systemic infection (postpone study entry until one week following recovery. * Known, uncontrolled serious systemic disease and/or life expectancy less than 12 months. * Concurrent participation in another investigational drug or device study or participation in the 30 days immediately prior to study enrollment. * Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study. * Patients whose pain is rated as less than 4.5 on a 10 point Numerical Pain Rating scale at the screening visit * Patients on coumadin or heparin because of increased risk of bleeding in the joint * Serious or unstable psychiatric disease or cognitive impairment that would limit evaluation of response to treatment. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Maren L Mahowald, MD **Phone:** 6124674190 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Jasvinder A Singh, MD, MPH **Phone:** 6124674190 **Role:** CONTACT #### Locations **Location 1:** **City:** Minneapolis **Contacts:** ***Contact 1:*** - **Name:** Maren L Mahowald, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 2:*** - **Name:** Jasvinder A Singh, MD MPPH - **Role:** SUB_INVESTIGATOR ***Contact 3:*** - **Name:** Hollis E Krug, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Minneapolis VAMC **State:** Minnesota **Status:** RECRUITING **Zip:** 55417 #### Overall Officials **Official 1:** **Affiliation:** Minneapolis VAMC **Name:** Maren L Mahowad, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007592 - Term: Joint 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: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M4476 - Name: Arthritis - Relevance: HIGH - As Found: Arthritis - ID: M20833 - Name: Arthralgia - 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: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001168 - Term: Arthritis ### 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: M5183 - Name: Botulinum Toxins - Relevance: HIGH - As Found: Face - ID: M21257 - Name: Botulinum Toxins, Type A - Relevance: HIGH - As Found: Weight loss - ID: M250193 - Name: abobotulinumtoxinA - Relevance: HIGH - As Found: Weight loss - 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: D000001905 - Term: Botulinum Toxins - ID: D000019274 - Term: Botulinum Toxins, Type A - ID: C000542869 - Term: abobotulinumtoxinA ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04469179 **Brief Title:** Safety, Tolerability, and Pharmacokinetics of SAB-185 in Ambulatory Participants With COVID-19 **Official Title:** A Phase 1B, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of SAB-185 in Ambulatory Subjects With COVID-19 #### Organization Study ID Info **ID:** SAB-185-102 #### Organization **Class:** INDUSTRY **Full Name:** SAb Biotherapeutics, Inc. ### Status Module #### Completion Date **Date:** 2021-11 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2021-10-26 **Type:** ACTUAL **Last Update Submit Date:** 2021-10-25 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-02-25 **Type:** ACTUAL #### Start Date **Date:** 2020-08-20 **Type:** ACTUAL **Status Verified Date:** 2021-10 #### Study First Post Date **Date:** 2020-07-13 **Type:** ACTUAL **Study First Submit Date:** 2020-07-08 **Study First Submit QC Date:** 2020-07-10 ### Sponsor Collaborators Module #### Collaborators **Class:** FED **Name:** Biomedical Advanced Research and Development Authority **Class:** UNKNOWN **Name:** Joint Program Executive Office (JPEO) Chemical, Biological, Radiological, and Nuclear Defense (CBRND) Enabling Biotechnologies (EB) #### Lead Sponsor **Class:** INDUSTRY **Name:** SAb Biotherapeutics, 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:** : Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SAB Biotherapeutics has developed SAB-185, an Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (transchromosomic \[Tc\] bovine-derived), as a potential therapeutic to treat COVID-19. This study will evaluate the safety, immunogenicity, and pharmacokinetics of SAB-185 in ambulatory participants with COVID-19. ### Conditions Module **Conditions:** - COVID-19 - SARS-CoV2 ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 21 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 10mg/kg SAB-185 in normal (0.9%) saline; concentration 4mg/mL (0.4%) **Intervention Names:** - Biological: SAB-185 **Label:** Cohort 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 25mg/kg SAB-185 in normal (0.9%) saline; concentration 20mg/mL (2%) **Intervention Names:** - Biological: SAB-185 **Label:** Cohort 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** 50mg/kg SAB-185 in normal (0.9%) saline; concentration 20mg/mL (2%) **Intervention Names:** - Biological: SAB-185 **Label:** Cohort 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm. **Intervention Names:** - Other: Normal Saline **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Cohort 1 - Cohort 2 - Cohort 3 **Description:** SAB-185 is a purified human immunoglobulin G (hIgG) designed to specifically bind to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viruses. SAB-185 is purified from the plasma of immunized Tc bovines that were immunized initially (vaccinations 1 and 2) with a plasmid DNA (pDNA) vaccine that expresses wild-type SARS-CoV-2 spike protein, followed by additional immunizations (vaccinations 3 and beyond) with a recombinant spike protein from SARS-CoV-2 produced in insect cells. The purified hIgG is a sterile liquid formulated in 10 mM glutamic acid monosodium salt, 262 mM D-sorbitol, 0.05 mg/mL Tween 80, pH 5.5. The drug product will be administered intravenously and will be diluted in saline per the clinical protocol. **Name:** SAB-185 **Other Names:** - Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (Tc bovine-derived) **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Normal (0.9%) saline in approximately the same volume as each cohort in the experimental drug arm. **Name:** Normal Saline **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Incidence and severity of other adverse events and severe adverse events (SAE) **Measure:** Number of Participants Having Adverse Events **Time Frame:** 29 Days **Description:** transfusion-related adverse events **Measure:** Number of Participants Having Transfusion-Related Adverse Events **Time Frame:** 29 Days #### Secondary Outcomes **Description:** Incidence and severity of adverse events and SAEs from Screening through Study Day 90 **Measure:** Number of Participants Having Adverse Events **Time Frame:** 90 Days **Description:** Measurement of SARS CoV-2 neutralizing (PRNT80) antibody titers from screening through Study Day 90 **Measure:** Assesment of the PD of SAB-185 administered intravenously **Time Frame:** 90 Days **Description:** Measurement of Rheumatoid factor through day 90 **Measure:** Immune response elicited by SAB-185 **Time Frame:** 90 Days **Description:** Measurement of anti-SAB-185 antibodies through screening day 90 **Measure:** Concentration of subject anti-SAB-185 antibodies elicited by SAB-185 **Time Frame:** 90 Days **Description:** Incidence of SARS-CoV-2 in swab specimens as measured by quantitative RT-PCR through Study Day 29 **Measure:** Incidence of SARS-CoV-2 in oropharyngeal (OP) or nasopharyngeal (NP) swab specimens **Time Frame:** 29 Days **Description:** Level of SARS-CoV-2 in swab specimens as measured by quantitative RT-PCR through Study Day 29 **Measure:** Level of SARS-CoV-2 in oropharyngeal (OP) or nasopharyngeal (NP) swab specimens **Time Frame:** 29 Days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Subjects must meet all of the following criteria for inclusion: 1. 18-60 years of age 2. Positive for presence of SARS-CoV-2 on NP or OP swab by FDA-authorized RT-PCR test within seven days prior to infusion 3. At least one current symptom of COVID-19, onset within seven days prior to infusion: * Fever or chills * Cough * Shortness of breath or difficulty breathing * Fatigue * Muscle or body aches * Headache * New loss of taste or smell * Sore throat * Congestion or runny nose * Nausea or vomiting * Diarrhea 4. Able to understand the study and comply with all study procedures 5. Agrees not to participate in any other trial of an investigational product during the study period 6. Willing and able to provide written informed consent prior to the start of any study related activities 7. If female, meets at least one of the following reproductive risk criteria * Post-menopausal for at least 12 months * Use of one or more of the following highly effective contraceptive methods for at least 90 days following the last dose of study product: combined estrogen and progestogen containing or progestogen-only hormonal contraception, intrauterine device (IUD), intrauterine hormone-releasing system, surgical bilateral tubal occlusion * Vasectomized sole sexual partner who has received medical assessment of the surgical success 8. Male and female subjects agree to sexual abstinence (refraining from heterosexual intercourse for at least 90 days following the last dose of study product) if not using birth control or condoms for males. Exclusion Criteria: Subjects who meet any of the criteria of severe or higher COVID-19 will be excluded from the study: * Dyspnea at rest * Respiratory rate \> 30 breaths per minute * SpO2 ≤ 93% on room air * Heart rate ≥ 125 beats per minute * Respiratory distress or respiratory failure. * Evidence of critical illness 1. Female subjects with positive pregnancy test, breastfeeding, or planning to become pregnant/breastfeed during the study period. 2. Hospitalization or need for hospitalization for any cause 3. Treatment or participation in another clinical trial of any other investigational agent within 30 days prior to enrollment. 4. Use of other drugs that, in the opinion of the investigator, could complicate analysis of SAB-185. 5. Subjects with the following risk factors: * Compromised immune system including confirmed diagnosis of current cancer under treatment, inherited deficiencies of the immune system, immune suppressing medication, or other conditions causing leukopenia or neutropenia * Known autoimmune condition requiring therapy more intensive than intermittent non-steroidal anti-inflammatories in the prior 6 months (for example: rheumatoid arthritis, lupus, inflammatory bowel disease) * Chronic respiratory disease including COPD, emphysema, cystic fibrosis, pulmonary hypertension, or other chronic condition that requires the routine use of supplemental oxygen * Chronic asthma requiring the use of oral steroids or hospitalization in the last six months * Renal failure or renal insufficiency requiring dialysis * Congestive heart failure or significant atherosclerotic disease (coronary artery disease or peripheral vascular disease) 6. Receipt of pooled immunoglobulin or plasma in past 30 days 7. Any other underlying medical (cardiac, liver, renal, neurological, respiratory) or psychiatric condition that in the view of the investigator would preclude use of SAB-185 8. Known IgA deficiency or previous allergic reaction to intravenous immunoglobin (IVIG)/subcutaneous immunoglobin (SCIG) 9. Positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or HIV antibody by medical history 10. History of allergy, anaphylaxis, or severe reaction to beef products (including milk and gelatin). **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Miami Beach **Country:** United States **Facility:** Quantum Clinical Trials **State:** Florida **Zip:** 33140 **Location 2:** **City:** Omaha **Country:** United States **Facility:** University of Nebraska Medical Center **State:** Nebraska **Zip:** 68198 **Location 3:** **City:** Sioux Falls **Country:** United States **Facility:** Sanford Health **State:** South Dakota **Zip:** 57117 #### Overall Officials **Official 1:** **Affiliation:** ICON GPHS **Name:** David Hoover, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Anyone who wishes to access the data. **Description:** Individual participant data that underlie the results reported in the published article, after deidentification (test, tables, figures, and appendices) **Info Types:** - STUDY_PROTOCOL **IPD Sharing:** YES **Time Frame:** Starting 6 months after publication and ending 36 months following article publication ### References Module #### References **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 ## 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 - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: HIGH - As Found: Colorectal Cancer - ID: M10122 - Name: Immunoglobulin G - Relevance: LOW - As Found: Unknown - ID: M19117 - Name: Immunoglobulins, Intravenous - Relevance: HIGH - As Found: American Indian - ID: M15814 - Name: Sorbitol - Relevance: LOW - As Found: Unknown - ID: M12147 - Name: Myeloma Proteins - Relevance: LOW - As Found: Unknown - ID: M13179 - Name: Paraproteins - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: T5 - Name: Glutamic Acid - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000007136 - Term: Immunoglobulins - ID: D000016756 - Term: Immunoglobulins, Intravenous ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05267379 **Acronym:** G-PEP **Brief Title:** An European Multi-centre Cohort Study for Unravelling Pharmacokinetic and Genetic Factors Underlying Post-ERCP Pancreatitis **Official Title:** An European Multi-centre Cohort Study for Unravelling Pharmacokinetic and Genetic Factors Underlying Post-ERCP Pancreatitis #### Organization Study ID Info **ID:** 108224 #### Organization **Class:** OTHER **Full Name:** Radboud University Medical Center ### Status Module #### Completion Date **Date:** 2025-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-11 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-10 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-12-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-03-01 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2022-03-04 **Type:** ACTUAL **Study First Submit Date:** 2022-01-24 **Study First Submit QC Date:** 2022-02-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Radboud 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:** Endoscopic retrograde cholangiopancreatography (ERCP) comes with a risk for post-ERCP pancreatitis (PEP), which accounts for considerable morbidity, high healthcare expenditure, and death. The pathophysiology of PEP and the underpinnings of the preventive effect of rectal NSAID (RN) is poorly understood. Guidelines advise to take preventive measures with a single dose of 100mg RN, peri-ERCP. While NSAID administration reduces the risk with 40%, PEP still occurs after ERCP. In addition, patients with a PEP history have a higher risk to develop recurrence after a subsequent ERCP. This might suggest that an underlying genetic risk may contribute to increasing the incidence of PEP in some patients. **Detailed Description:** This study is a hypothesis driven and hypothesis free analyses of PEP risk variants. Integrative analysis of NSAID pharmacokinetics and-genetics in PEP patients. ### Conditions Module **Conditions:** - Post-ERCP Acute Pancreatitis ### Design Module #### Bio Spec **Description:** Blood samples **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 700 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients who develop PEP **Intervention Names:** - Diagnostic Test: Take blood samples **Label:** PEP patients #### Arm Group 2 **Description:** Patients who do not develop PEP **Intervention Names:** - Diagnostic Test: Take blood samples **Label:** Control cohort ### Interventions #### Intervention 1 **Arm Group Labels:** - Control cohort - PEP patients **Description:** Blood samples are used to check for polymorphisms in NSAID metabolization genes and to determine the diclofenac levels. **Name:** Take blood samples **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Analyzing differences in polymorphisms in NSAID metabolization genes between PEP patients and control patients using Taqman assay. DNA will be isolated from blood samples and analyzed for SNP's of biotransformation enzymes such as UDP-Glucuronosyltransferase-2B7 (UGT2B7) and CYP2C9. This will be done using polymerase chain reaction (PCR) with fluorescent probes specific for a SNP (Taqman assay) **Measure:** Differences in SNP's in NSAID metabolization genes **Time Frame:** 1 month #### Secondary Outcomes **Description:** Detection of diclofenac levels two hours after diclofenac administration. Levels will be measured in blood samples by high-performance liquid chromatography (HPLC). **Measure:** Diclofenac levels **Time Frame:** 2 hours **Description:** To investigate whether there is a correlation between diclofenac levels and NSAID metabolism gene polymorphisms. Using an independent t-test, the investigators will try to find a significant correlation between the diclofenac levels and a difference in single nucleotide polymorphism (SNP). **Measure:** Correlation diclofenac levels and NSAID metabolization gene polymorphisms **Time Frame:** 1 month **Description:** To investigate whether the known genes involved in developing acute pancreatitis also are involved in developing PEP. DNA isolated from the blood samples will be analyzed by Miniseq-technique. **Measure:** Genes involved in development of PEP **Time Frame:** 1 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age ≥ 18 years * written informed consent * Indication to undergo an ERCP Exclusion Criteria: * Pancreatic cancer * Chronic pancreatitis * Ongoing acute pancreatitis * Altered anatomy, defined as anatomical variations in which gall and/or pancreatic juices (in case of pancreatic duct interventions) do not enter the duodenum by way of the ampulla of Vater. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients aged 18 years or older with an indication to undergo an ERCP, without pancreatic cancer, chronic pancreatitis, altered anatomy of the upper digestive tract and an ongoing acute pancreatitis. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mike de Jong, MD **Phone:** 0031883207054 **Role:** CONTACT #### Locations **Location 1:** **City:** Nijmegen **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mike de Jong, MD - **Phone:** 0031883207054 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Erwin van Geenen, MD, PhD - **Phone:** 0031243619190 - **Role:** CONTACT **Country:** Netherlands **Facility:** RadboudUMC **State:** Gelderland **Status:** RECRUITING **Zip:** 6525 GA #### Overall Officials **Official 1:** **Affiliation:** Radboud University Medical Center **Name:** Erwin van Geenen, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** The dataset used during this study is available from the corresponding author upon reasonable request. **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010182 - Term: Pancreatic Diseases - ID: D000004066 - Term: Digestive System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13115 - Name: Pancreatitis - Relevance: HIGH - As Found: Pancreatitis - ID: M13102 - Name: Pancreatic 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: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010195 - Term: Pancreatitis ### 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: M7197 - Name: Diclofenac - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03260179 **Brief Title:** Study to Evaluate the Safety, Preliminary Efficacy and Pharmacokinetics of 3810 **Official Title:** An Open-label Phase Ib, Study, to Determine Safety of Oral AL3810 in Patients With Locally Advanced or Metastatic Gastric, Hepatocellular or Nasopharyngeal Carcinoma #### Organization Study ID Info **ID:** CL1-80881-008 #### Organization **Class:** INDUSTRY **Full Name:** Haihe Biopharma Co., Ltd. ### Status Module #### Completion Date **Date:** 2019-06-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2017-08-24 **Type:** ACTUAL **Last Update Submit Date:** 2017-08-21 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-01-31 **Type:** ESTIMATED #### Start Date **Date:** 2017-08-31 **Type:** ESTIMATED **Status Verified Date:** 2017-08 #### Study First Post Date **Date:** 2017-08-24 **Type:** ACTUAL **Study First Submit Date:** 2017-07-20 **Study First Submit QC Date:** 2017-08-21 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Shanghai Institute of Materia Medica, Chinese Academy of Sciences #### Lead Sponsor **Class:** INDUSTRY **Name:** Haihe Biopharma Co., Ltd. #### 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 project intends to make a study of personalized medicine evaluation system establishment for liver cancer, gastric cancer and nasopharynx cancer to provide strong support for the development of Precision Medicine and personalized medicine for the patients of high-incidence-rates cancer in China. ### Conditions Module **Conditions:** - Advanced Solid Tumor - Advanced/Metastatic Colorectal Cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 20 gastric carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 **Intervention Names:** - Drug: AL3810 **Label:** gastric carcinoma **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 20 hepatocellular carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 **Intervention Names:** - Drug: AL3810 **Label:** hepatocellular carcinoma **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** 20 Nasopharyngeal carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 **Intervention Names:** - Drug: AL3810 **Label:** Nasopharyngeal carcinoma **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - gastric carcinoma **Description:** Fasting，oral ，4w on or 3w on/1w off **Name:** AL3810 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - hepatocellular carcinoma **Description:** Fasting，oral ，4w on or 3w on/1w off **Name:** AL3810 **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Nasopharyngeal carcinoma **Description:** Fasting，oral ，4w on or 3w on/1w off **Name:** AL3810 **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** cell count of CD4+/CD8+ **Measure:** CD4+/CD8+ **Time Frame:** from baseline up to six months(every 8 weeks±7 days ) **Description:** the content of growth factor such as VEGF，FGF and PDGF in plasma **Measure:** Growth factor **Time Frame:** from baseline up to six months(every 8 weeks±7 days ), C1D15 **Description:** the content of growth factor such as INFγ and cMyc in plasma **Measure:** Exosomes **Time Frame:** from baseline up to six months(every 8 weeks±7 days ) #### Primary Outcomes **Description:** the number of patients with grade 3 and 4 AE according to CTC AE 4.03 **Measure:** AE **Time Frame:** through study completion, an average of 1 year #### Secondary Outcomes **Description:** The proportion of patients who have observed overall remission (CR) or partial remission (PR) as the overall optimal remission based on the RECIST 1.1. **Measure:** ORR **Time Frame:** through study completion, an average of 1 year **Description:** Area under the plasma concentration versus time curve **Measure:** AUC **Time Frame:** up to 3 cycles(28 days/cycle) **Description:** Peak Plasma Concentration **Measure:** Cmax **Time Frame:** up to 3 cycles(28 days/cycle) **Description:** All patients with the best overall response to CR or PR were required to calculate the duration of the response. This time is the duration (progression or death, whichever occurs first) from the first decision to CR or PR to tumor progression or death (death for any cause) **Measure:** DoR **Time Frame:** through study completion, an average of 1 year **Description:** DCR refers to the percentage of patients who have achieved confirmation during the treatment of CR, confirmed PR and / or SD **Measure:** DCR **Time Frame:** through study completion, an average of 1 year **Description:** To the date of randomization to the date of the onset of the disease or the date of death (regardless of the cause of the death) (whichever is the earlier). **Measure:** PFS **Time Frame:** through study completion, an average of 1 year ### Eligibility Module **Eligibility Criteria:** Main criteria for inclusion: 1. Adult male or female Chinese subject aged 18 to 70 years, inclusive, at the time of signing the informed consent form, with weight at least 40 kg when screening. 2. Life expectancy ≥ 12 weeks as judged by the Investigator. 3. Histologically or cytologically confirmed, locally advanced or metastatic solid tumor and be limited to: * Gastric carcinoma (including gastro-oesophageal junction adenocarcinoma). * Hepatocellular carcinoma (Child-Pugh Class A). * Undifferentiated nasopharyngeal carcinoma. 4. Each subject should provide at least 5 slides for the formalin fixed and paraffin embedded tumor biopsy (undyed) at the baseline, fresh biopsy or most recent primary tumor sample or metastatic sample is required. 5. Patients, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists. 6. Toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade ≤ 1 as per the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), excluding alopecia and peripheral neuropathy. For subjects having a prior platinum-based therapy, peripheral neuropathy are required to recover to ≤ CTCAE grade 2. 7. Per RECIST v1.1 guidelines for solid tumors: * Patients with gastric carcinoma should have at least one measurable lesion beyond stomach, * Patients with Hepatocellular carcinoma and undifferentiated nasopharyngeal carcinoma should have at least one measurable lesion. 8. Adequate bone marrow and organ function as defined by the following laboratory values: (prophylactic use of myeloid growth factors (eg, G-CSF, GM-CSF) is prohibited within 2 weeks before screening) * Absolute neutrophil count (ANC) ≥ 1.5x 109/L. * Platelet counts ≥ 100 x 109/L. * Haemoglobin ≥ 90 g/L (without blood transfusion within the last 2 weeks from screening). * Creatinine clearance \> 50 mL/min (calculated according to Cockroft-Gault formula). * Proteinuria \< 1+. If proteinuria ≥ 1+, urine protein quantitation over 24 hours should be \< 1.0 g/24hrs. * INR ≤ 1.5 and APTT≤ 1.5 Upper Limit of Normal (ULN). * AST, ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases or hepatocellular carcinomas are present). * Total Bilirubin \< 1.5 x ULN. * For Hepatocellular carcinomas patients, albumin ≥ 28 g/dL. 9. Patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1. 10. Patient is able to swallow and retain oral medication. 11. Female subjects, with childbearing potential, has a negative serum pregnancy test at screening (within 7 days of the first investigational product administration). The definition of women with child-bearing potential are defined as "All female subjects after puberty unless they are post-menopausal or not sexually active". Females are considered postmenopausal if they have age-related amenorrhea ≥ 12 consecutive months or if they have undergone hysterectomy or bilateral oophorectomy. 12. Patients who have fully understood the study, and have signed the general Informed Consent Form (ICF) prior to any screening procedures being performed Main criteria for non-inclusion 1. Patient who has participated in another interventional trial within 28 days prior to starting study medicine. If a subject is joining a non-interventional trial, such as an epidemiological study, or in a survival follow-up period of an interventional trial, he or she may participate in this trial. 2. Expected poor compliance during the study. 3. Patient has symptomatic CNS metastases requiring clinical intervention. The stable patient may participate in this trial, who must have completed any prior local treatment for CNS metastases ≥ 14 days prior to the start of study treatment (including radiotherapy and/or low dose steroid therapy). 4. Patient has a concurrent malignancy or malignancy within 2 years of study enrolment, with the exception of adequately treated and cured non-melanomatous skin cancer, carcinoma in situ of breast and cervix, and superficial bladder cancer. 5. Patient who has received chemotherapy, targeted therapy or immunotherapy within 28 days or ≤ 5 half-lives prior to starting study medicine. Take the longer one. For HCC patient who has received any prior local therapy (hepatic arterial embolization, transcatheter arterial chemoembolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) within 4 weeks of starting study medicine •. 6. Previous treatment with Bevacizumab within 3 months of starting AL3810. In addition: - Patients with nasopharyngeal carcinoma who received antiangiogenic agent are not allowed. 7. Patients with nasopharyngeal carcinoma located within 5mm of large blood vessels. 8. Patient who has received wide field radiotherapy within 28 days prior to starting study medicine 9. Patient who has received a major surgery within 28 days prior to starting study medicine. The definition of a major surgery refers to grade 3 and 4 surgery specified in \<Management of Clinical Practice of Medical Technologies\> effective on May 1, 2009 in China, 10. Patient has active cardiac disease or a history of cardiac dysfunction in screening including any of the following: * History of documented Congestive heart failure ≥ class II (NYHA New York Heart Association functional classification) or requiring therapy, * Ventricular and/or supraventricular arrhythmia requiring therapy; * Severe conduction disturbance (including QTc interval prolongation \> 450msec \[corrected by Fredericia formula\], history of severe arrhythmia, or history of familial arrhythmia \[e.g., Wolff-Parkinson-White syndrome\]), * Angina pectoris requiring therapy, * Left ventricular ejection fraction (LVEF) \< 50% evaluated by cardiac ultrasound (ECHO) or Multi Gated Acquisition Scan (MUGA) , * Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg with optimized antihypertensive therapy or patients treated with ≥ 2 antihypertensive agents), * Hypertension with systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg with or without antihypertensive therapy. * Conduction abnormality requiring a pacemaker or implanted a pacemaker. 11. History of clinically significant or uncontrolled cardiac disease within 6 months prior to starting AL3810, including angina, myocardial infarction, and stroke. 12. Patients with thromboembolic events within 12 months prior to starting AL3810, or at a high risk of such events. 13. Patient with hereditary risks of thromboembolic events. 14. Patient is currently receiving treatment with warfarin or any other oral Anticoagulants 15. Patients with active HBV or HCV infection or known positivity for human immunodeficiency virus (HIV) infection are not allowed. HBV, HCV and HIV will be tested in the screening. Serum HBsAg positive with HBV DNA \<104 Copy/mL may participate study. Prophylactic anti-HBV medications application can be accepted. Serum HCV or HIV antibody positive is not allowed. 16. Patients receiving medications known to prolong QTc interval and that may be associated with Torsades de Pointes. 17. Serum potassium (K+) levels below LLN at screening period. 18. Patients who received administration of strong inhibitors of CYP2C8 and/or CYP3A4 or strong inducers of CYP3A4 within 7 days or ≤ 5 half-lives (Take the longer one) prior to starting AL3810. And patient cannot stop taking the medication. . 19. Significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhoea associated with intestinal malabsorption, the Crohn's disease, or significant abnormalities decided by investigator. In addition, patients with any grade of gastro-intestinal bleeding events within 3 months prior to starting AL3810 are not allowed. 20. History of grade 3 haemorrhage/bleeding events within 6 months prior to starting AL3810, or history of grade 4 haemorrhage/bleeding events. 21. Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, thyroid and adrenal gland. 22. Serious/active bacterial, viral or fungal infection requiring systemic treatment. 23. Concomitant uncontrolled severe systemic disease (e.g., uncontrolled diabetes mellitus, uncontrolled ascites, etc.). 24. Psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study procedures. 25. Known organ dysfunction which would either compromise the patient's safety or interfere with the evaluation of AL3810. 26. Male patients and female patients of child bearing potential unable or unwilling to employ effective contraception (abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive for women and barrier method) during the study and for 6 months thereafter. 27. Breastfeeding women. **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Qin Shu kui, MD **Phone:** 13905158713 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Hua Hai qing, MD **Phone:** 13951807023 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Name:** Xu Jian ming, MD - **Role:** CONTACT **Country:** China **Facility:** The 307th Hospital of Chinese People's Liberation Army **State:** Beijing **Location 2:** **City:** Guangzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Xu Rui hua, MD - **Phone:** 13922206676 - **Role:** CONTACT **Country:** China **Facility:** Sun Yat-sen University Cancer Center **State:** Guangdong **Location 3:** **City:** Guangzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Zhang li, MD - **Phone:** 13902282893 - **Role:** CONTACT **Country:** China **Facility:** Sun Yat-sen University **State:** Guangdong **Location 4:** **City:** Nanjing **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Qin Shu kui, MD - **Phone:** 13905158713 - **Role:** CONTACT **Country:** China **Facility:** The 81st Hospital of People's Liberation Army **State:** Jiangsu **Zip:** 210002 **Location 5:** **City:** Nanjing **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Feng Ji feng, MD - **Phone:** 13901581264 - **Role:** CONTACT **Country:** China **Facility:** Jiangsu Cancer Hospital **State:** Jiangsu **Location 6:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Cao Jun ning, MD - **Phone:** 13651680209 - **Role:** CONTACT **Country:** China **Facility:** Fudan University Shanghai Cancer Center **State:** Shanghai **Zip:** 200000 **Location 7:** **City:** Hangzhou **Country:** China **Facility:** Sun Yat-sen University Cancer Center **State:** Zhejiang ### References Module #### References **Citation:** Zhang Y, Luo F, Ma YX, Liu QW, Yang YP, Fang WF, Huang Y, Zhou T, Li J, Pan HM, Yang L, Qin SK, Zhao HY, Zhang L. A Phase Ib Study of Lucitanib (AL3810) in a Cohort of Patients with Recurrent and Metastatic Nasopharyngeal Carcinoma. Oncologist. 2022 Jun 8;27(6):e453-e462. doi: 10.1093/oncolo/oyab076. **PMID:** 35445718 ## 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: All - Name: All Conditions - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M1730 - Name: Nasopharyngeal Carcinoma - Relevance: LOW - As Found: Unknown - 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 - ID: T4047 - Name: Nasopharyngeal Carcinoma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015179 - Term: Colorectal Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00718679 **Acronym:** IVN-CAT-001B **Brief Title:** Evaluation of Safety, Tolerability, Immunogenicity and Efficacy of a Novel Method in Specific Immunotherapy in Cat Allergic Patients: a Placebo Controlled Trial **Official Title:** Evaluation of Safety, Tolerability, Immunogenicity and Efficacy of a Novel Method in Specific Immunotherapy in Cat Allergic Patients: a Placebo Controlled Trial #### Organization Study ID Info **ID:** IVN-CAT-001B #### Organization **Class:** OTHER **Full Name:** University of Zurich ### Status Module #### Completion Date **Date:** 2010-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2010-02-11 **Type:** ESTIMATED **Last Update Submit Date:** 2010-02-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-02 **Type:** ACTUAL #### Start Date **Date:** 2008-07 **Status Verified Date:** 2010-02 #### Study First Post Date **Date:** 2008-07-21 **Type:** ESTIMATED **Study First Submit Date:** 2008-07-18 **Study First Submit QC Date:** 2008-07-18 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** ImVision GmbH, Hannover #### Lead Sponsor **Class:** OTHER **Name:** University of Zurich #### Responsible Party **Old Name Title:** PD Dr. Thomas Kündig **Old Organization:** University Hospital Zurich ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is placebo controlled, double blind, randomised, two arm dose escalation of a new product for specific immunotherapy in cat allergic patients ### Conditions Module **Conditions:** - Allergy to Cat Dander ### 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:** 20 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Study drug **Intervention Names:** - Drug: IVN201 **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo **Intervention Names:** - Drug: Placebo **Label:** 2 **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** Intralymphativ injection of the study drug **Name:** IVN201 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 2 **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Saftety tolerability and efficacy **Time Frame:** 2009 ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * History and subjective symptoms of cat dander allergy including cat specific allergic rhinitis * Age 18 to 65 years * Positive reaction to at least one concentration of cat dander allergen in skin prick test, intradermal provocation test and nasal provocation test Exclusion criteria: * Chronic infectious disease * Acute infections * Episode of non-allergic rhinitis within the last 4 weeks * Use of allergen known to predict anaphylactic reactions * Treatment with any other investigational drug within 3 months before trial entry * Vaccination within the last week * Nasal surgery within the last 8 weeks * Progressive fatal disease * Drug or alcohol abuse within the last 5 years * Cat ownership * A history of significant cardiac insufficiency (NYHA stage III-IV) * Coexisting severe disease, e.g. cardiovascular diseases * Acute or history of obstructive respiratory insufficiency ( FEV1 \<70%) * Hepatic insufficiency * Relevant anaemia (as judged by investigator) * Blood donation within the last 30 days or intended blood donation (during the study or 30 days after participation) * Pregnancy or breast feeding * Sexually active woman of childbearing potential not actively practicing birth control by using a medically accepted device or therapy * Lack of compliance or other sililar reason, that the investigator believes, precludes satisfactory participation in the study * Systemic glucocorticoid therapy * Allergic asthma and chronic medication with steroids at doses exceeding 200ug/day Treatment with ATII antagonists, B-blocker, ACE inhibitors **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Zurich **Country:** Switzerland **Facility:** Center for Clinical Research University Hospital Zurich #### Overall Officials **Official 1:** **Affiliation:** UniversitaetsSpital Zuerich **Name:** Gabriela Senti, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Freiberger SN, Zehnder M, Gafvelin G, Gronlund H, Kundig TM, Johansen P. IgG4 but no IgG1 antibody production after intralymphatic immunotherapy with recombinant MAT-Feld1 in human. Allergy. 2016 Sep;71(9):1366-70. doi: 10.1111/all.12946. Epub 2016 Jun 17. **PMID:** 27253988 **Citation:** Senti G, Crameri R, Kuster D, Johansen P, Martinez-Gomez JM, Graf N, Steiner M, Hothorn LA, Gronlund H, Tivig C, Zaleska A, Soyer O, van Hage M, Akdis CA, Akdis M, Rose H, Kundig TM. Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J Allergy Clin Immunol. 2012 May;129(5):1290-6. doi: 10.1016/j.jaci.2012.02.026. Epub 2012 Mar 30. **PMID:** 22464647 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M2853 - Name: Immunomodulating Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04985279 **Brief Title:** Position and Angle Marking System (PAMS) for Ultrasound-guided Neuraxial Procedures **Official Title:** Position and Angle Marking System (PAMS) for Ultrasound-guided Neuraxial Procedures #### Organization Study ID Info **ID:** PAMS 2021/2159 #### Organization **Class:** OTHER_GOV **Full Name:** KK Women's and Children's Hospital ### Status Module #### Completion Date **Date:** 2021-08-31 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-08-02 **Type:** ACTUAL **Last Update Submit Date:** 2021-07-30 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-08-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-08-01 **Type:** ESTIMATED **Status Verified Date:** 2021-07 #### Study First Post Date **Date:** 2021-08-02 **Type:** ACTUAL **Study First Submit Date:** 2021-07-05 **Study First Submit QC Date:** 2021-07-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** KK Women's and Children's Hospital #### Responsible Party **Investigator Affiliation:** KK Women's and Children's Hospital **Investigator Full Name:** Paul Tan Hon Sen **Investigator Title:** Associate Consultant **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Epidural anaesthesia involves the administration of numbing medication (local anaesthetics) close to the spinal canal, and is regarded as the best method for providing pain relief during labour and childbirth. The use of ultrasound to guide epidural insertion and placement has been shown to improve pain relief and reduce the risk of complications. However, after identifying the desired needle insertion site via ultrasound, current practice involves demarcating the insertion site using marker pens, which is time-consuming, inaccurate, and may be inadvertently removed by skin sterilisation. Furthermore, the desired needle angulation determined by ultrasound cannot be accurately measured and maintained during the epidural procedure. Both issues limit the benefits of using ultrasound to guide the epidural procedure. To address these issues, the investigators developed a Position and Angular Marking System (PAMS) that attaches on to the ultrasound probe. When the desired insertion site is identified by ultrasound, the doctor gently presses PAMS into the patient's back to create skin indentations demarcating the needle insertion point. These indentations are not affected by skin sterilisation, and may improve accuracy and reduce the time taken to perform the epidural procedure. Next, the angle between the ultrasound probe and the patient's back can be measured using PAMS, and this angle can be maintained using a needle guide during the epidural procedure. The purpose of this randomised study is to evaluate the usability of PAMS and to identify areas for further improvement. This study will involve up to 10 healthy simulated patients, and up to 30 volunteer ultrasound operators. After undergoing a standardised training session with a mannequin, the ultrasound operators will be randomly assigned to perform skin marking on the simulated patients as though they are performing an ultrasound-guided epidural anaesthesia procedure (no needle puncture will be made) using either PAMS, or standard clinical practice with marker pens. After completing the procedure, the ultrasound operators will cross over and perform the procedure again using either PAMS or standard clinical practice with marker pens. Both the ultrasound operators and simulated patients will be asked to complete satisfaction and usability surveys regarding their experience with the procedures. **Detailed Description:** The volunteer ultrasound operators are women's anaesthesiologists trained in the use of ultrasound-guided neuraxial procedures. Simulated patients are healthy volunteers from other departments, without spine abnormalities. The ultrasound operators will be asked to complete a questionnaire regarding your prior experience with neuraxial ultrasonography and undergo structured training on the use of PAMS using a mannequin. Next, they will be asked to perform the following two procedures (the order at which they will perform the procedures will be randomised): 1. Ultrasound scan using PAMS * After attaching PAMS to the ultrasound probe, they will perform a lumbar ultrasound scan on a simulated patient to identify the desired needle insertion site and gently press PAMS into the simulated patient's back to create skin indentations demarcating the desired needle insertion site. * Next, adjust the angulation of the ultrasound probe to optimise the image of the simulated patient's lumbar spine, and read the angle between the ultrasound probe and patient's back off a graduated scale. * Remove the ultrasound probe, and position the needle-insertion guide corresponding to the skin indentations. Needle angulation can be simulated by mounting a blunt needle on to the insertion guide. * Finally, they will be asked to complete a usability questionnaire. 2. Ultrasound scan without PAMS (standard clinical practice) * Perform a lumbar ultrasound scan to identify the desired needle insertion site, followed by demarcation using skin markers. * Next, adjust the angulation of the ultrasound probe to optimise the image of the simulated patient's lumbar spine. * Remove the ultrasound probe and simulate needle insertion by touching the tip of a blunt needle to the patient's back, at the desired angle. * Finally, they will then be asked to complete a usability questionnaire. Both procedures are non-invasive (i.e. no skin punctures will be made). No follow up is required for this study. No new research medications are involved in this study. Additionally, video recordings may be made of the procedures. Any video or ultrasound images obtained during the course of this study will be stored and analysed only for the purposes of this study for a period not exceeding 7 years, and will be destroyed after completion of the study. Technical data such as the scanning duration and success rate will also be documented. ### Conditions Module **Conditions:** - Ultrasound-guided Neuraxial Procedures **Keywords:** - Ultrasonography - Epidural - Spinal - Labour analgesia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** The ultrasound operators will be randomised to perform either 1. Skin marking after lumbar ultrasonography using marker pens (standard practice) 2. Skin marking after lumbar ultrasonography using PAMS After completion of the first procedure, the ultrasound operators will then crossover and perform the other procedure. ##### Masking Info **Masking:** NONE **Masking Description:** No masking involved. **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** * Lumbar ultrasound scan will be performed to identify the desired needle insertion site, followed by demarcation using skin markers. * The angulation of the ultrasound probe will be adjusted to optimise the image of the simulated patient's lumbar spine. * The ultrasound probe will be removed and needle insertion simulated by touching the tip of a blunt needle to the patient's back, at the desired angle. * A usability questionnaire regarding the procedure will be completed. **Intervention Names:** - Device: Standard clinical practice **Label:** Standard clinical practice **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** * PAMS will be attached to the ultrasound probe. * Lumbar ultrasound scan will be performed to identify the desired needle insertion site, followed by demarcation by gentle pressing PAMS into the simulated patient's back to create skin indentations. * The angulation of the ultrasound probe will be adjusted to optimise the image of the simulated patient's lumbar spine, and the angle read off a graduated scale. * The ultrasound probe will be removed and needle insertion simulated by touching the tip of a blunt needle to the patient's back, at the desired angle. * A usability questionnaire regarding the procedure will be completed. **Intervention Names:** - Device: Position and Angle Marking System **Label:** Position and Angle Marking System (PAMS) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Position and Angle Marking System (PAMS) **Description:** Position and Angular Marking System (PAMS) attaches on to the ultrasound probe. When the desired insertion site is identified by ultrasound, the doctor gently presses PAMS into the patient's back to create skin indentations demarcating the needle insertion point. These indentations are not affected by skin sterilisation, and may improve accuracy and reduce the time taken to perform the epidural procedure. Next, the angle between the ultrasound probe and the patient's back can be measured using PAMS, and this angle can be maintained using a needle guide during the epidural procedure. **Name:** Position and Angle Marking System **Other Names:** - PAMS **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Standard clinical practice **Description:** When the desired insertion site is identified by ultrasound, the doctor demarcate the needle insertion point using marker pens. **Name:** Standard clinical practice **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Satisfaction and feedback regarding the respective procedures **Measure:** Satisfaction survey of simulated patients and operators **Time Frame:** Immediately after performing the procedure #### Secondary Outcomes **Description:** Comparison of time taken to perform the interventional procedure (PAMS), versus standard clinical practice (control) **Measure:** Time taken to perform procedure **Time Frame:** Immediately after performing the procedure ### Eligibility Module **Eligibility Criteria:** Ultrasound operators Inclusion Criteria: * Anaesthesiologists * Trained in the use of ultrasound-guided neuraxial procedures Exclusion Criteria: * No experience with ultrasound-guided neuraxial procedures Simulated patients Inclusion Criteria: * Healthy, no significant medical comorbidity (American Society of Anesthesiologists Physical Status I or II) * No spinal abnormalities, or previous spinal surgery Exclusion Criteria: * Significant spinal abnormality * Previous spinal surgery **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:** Hon Sen Tan, MD **Phone:** +65 63947107 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Ban Leong Sng, MBBS **Phone:** +65 63941077 **Role:** CONTACT #### Locations **Location 1:** **City:** Singapore **Contacts:** ***Contact 1:*** - **Name:** Hon Sen Tan, MD - **Phone:** +65 63947107 - **Role:** CONTACT **Country:** Singapore **Facility:** KK Women's and Children's Hospital **Status:** RECRUITING **Zip:** 128038 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Tan HS, Sng BL, Sia ATH. Reducing breakthrough pain during labour epidural analgesia: an update. Curr Opin Anaesthesiol. 2019 Jun;32(3):307-314. doi: 10.1097/ACO.0000000000000713. **PMID:** 31045638 ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02602379 **Brief Title:** Evaluation of NoL Index and ANI After Nociceptive Stimulation at Different Infusion Rates of Remifentanil Infusion **Official Title:** Evaluation of NoL Index and ANI Variations After Nociceptive Stimulation Under Different Rates of Infusion of Intravenous Remifentanil in Patients Undergoing Laparotomies With Intraoperative Epidural Analgesia #### Organization Study ID Info **ID:** HMR14090 #### Organization **Class:** OTHER **Full Name:** Maisonneuve-Rosemont Hospital ### Status Module #### Completion Date **Date:** 2015-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-11-18 **Type:** ESTIMATED **Last Update Submit Date:** 2016-11-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-07 **Type:** ACTUAL #### Start Date **Date:** 2015-02 **Status Verified Date:** 2016-11 #### Study First Post Date **Date:** 2015-11-11 **Type:** ESTIMATED **Study First Submit Date:** 2015-10-25 **Study First Submit QC Date:** 2015-11-09 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Medasense Biometrics Ltd #### Lead Sponsor **Class:** OTHER **Name:** Maisonneuve-Rosemont Hospital #### Responsible Party **Investigator Affiliation:** Maisonneuve-Rosemont Hospital **Investigator Full Name:** Philippe Richebé **Investigator Title:** MD, PhD, Professor of anesthesiology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Contrary to "immobility" and, to a lesser extent, to the "hypnosis/unconsciousness" component of general anaesthesia, the monitoring of "analgesia" remains largely elusive, evaluated mainly through poorly sensitive and potentially undesirable changes in patients' vital signs. This has led the industry to pursue the development of various devices and indices based on other physiological parameters such as heart rate variability (HRV), electroencephalogram (EEG), skin conductance, to name only a few. To the best of the knowledge, none of these parameters on its own has shown sufficient capacity in detecting different degrees of pain/analgesia balance to gain wide clinical use. The purpose of this prospective observational study is to evaluate the response of a single-parameter index (the Analgesia Nociception Index \[ANI\]) and a multi-parameter index (the Nociception Level \[NoL\] Index) when patients under combined general anaesthesia/epidural anaesthesia for laparotomies are subjected to a standardized painful stimulus (a tetanic stimulation over the ulnar nerve at 70 mA, 100 Hz for 30 seconds) at different doses of remifentanil infusion at steady state (0,005 mcg/kg/min; 0,05 mcg/kg/min; 0,1 mcg/kg/min; 0,15 mcg/kg/min). With the painful stimulus held constant but the analgesia provided gradually increased, it is expected to characterize the response of these two indices to different levels of nociception/anti-nociception balance. **Detailed Description:** Patients scheduled for elective abdominal surgery by laparotomy (general surgery or gynaecological surgery) will receive a thoracic epidural (around T9-T10/T10-T11) and general anesthesia. Apart from standard monitoring, the ANI (derived from the EKG) and the NoL index (obtained via a finger probe) will be recorded. The epidural catheter will be injected with 6-10 ml of lidocaine 2% with epinephrine 5 mcg/ml to produce anesthetic level of neuraxial blocade and then be perfused with the same solution at 4-8 ml/hour. After incision and confirmation of adequate blocade with the epidural local anesthetic, the patient will receive a series of painful electric stimulation with a standard nerve stimulator applied over the ulnar nerve in tetanic mode for 30 seconds at 100 Hz and 70mA. Each stimulation will occur at a different rate of infusion of IV remifentanil at steady state (0,005 mcg/kg/min; 0,05 mcg/kg/min; 0,1 mcg/kg/min; 0,15 mcg/kg/min). A stimulation at 0,005 mcg/kg/min will be done before and after epidural loading with local anesthetics to look for altered variations in analysed parameters. The variation and the kinetic of the variations after stimulations will be observed for heart rate, mean blood pressure, BIS, ANI and NoL index. ### Conditions Module **Conditions:** - Pain **Keywords:** - Pain - Monitoring - Analgesia Nociception Index - NoL - Nociception Level - Remifentanil ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Single arm study. See Study description for a through description of the intervention. **Intervention Names:** - Other: Tetanic stimulation **Label:** Tetanic stimulation ### Interventions #### Intervention 1 **Arm Group Labels:** - Tetanic stimulation **Description:** Standard Tetanic stimulation will be used as the stimulus to evaluate responses of the intraoperative pain indexes (ANI and NoL) at different concentration of i.v. remifentanil during anesthesia. **Name:** Tetanic stimulation **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The electrical stimulus will be applied on the forearm of the asleep patient at different doses of iv remifentanil (0.005mcg/kg/min to a maximum of 0.15 mcg/kg.min during anesthesia for abdominal surgery with active intraoperative epidural pain management). It will be evaluated whether or not exists a correlation between the doses of iv remifentanil and the responses of the Nol index after electrical stimulus. **Measure:** Correlation between NoL index responses to electrical stimulus and the i.v. doses of remifentanil infusion given during anesthesia. The n of patients (40 in this study) is calculated on this primary outcome. **Time Frame:** At time of surgery #### Secondary Outcomes **Description:** Measure the NoL changes after a nociceptive stimulus at various intravenous remifentanil infusion doses. **Measure:** NoL index changes after a standardized electrical stimulus at 4 different concentrations of iv remifentanil infusion **Time Frame:** At time of surgery **Description:** Measure the ANI changes after a nociceptive stimulus at various intravenous remifentanil infusion doses. ANI being another uniparametric pain index. **Measure:** ANI index changes after a standardized electrical stimulus at 4 different concentrations of iv remifentanil infusion **Time Frame:** At time of surgery **Description:** Measure the changes of Heart Rate after a nociceptive stimulus at various intravenous remifentanil infusion doses. **Measure:** Heart rate changes after a standardized electrical stimulus at 4 different concentrations of iv remifentanil infusion **Time Frame:** At time of surgery **Description:** Measure the changes of Heart Rate after a nociceptive stimulus at various intravenous remifentanil infusion doses. **Measure:** Mean Blood Pressure changes after a standardized electrical stimulus at 4 different concentrations of iv remifentanil infusion **Time Frame:** At time of surgery **Description:** Measure the sensitivity and specificity of these 4 criteria in detecting a painful stimulus such as intubation and standardized electrical stimulus **Measure:** Sensitivity and specificity of NoL index, ANI index, Heart Rate and Mean blood Pressure in detecting a painful stimulus such as intubation as well as standardized electrical stimulus at remifentanil infusion of 0.005 msg/kg/min **Time Frame:** At time of surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ASA status I, II or III * Elective abdominal surgery with median laparotomy under general anaesthesia and epidural analgesia. Exclusion Criteria: * Coronary artery disease * Serious cardiac arrhythmias (including atrial fibrillation) * Patient refusal * History of substance abuse * Chronic use of psychotropic and/or opioid drugs * Use of drugs that act on the autonomic nervous system (including β-blockers) * History of psychiatric diseases or psychological problems * Contraindications to epidural analgesia * Allergy to remifentanil * Unexpected difficult airway requesting excessive, possibly painful airway manipulations. * Dural puncture during epidural catheter installation * Failure of epidural analgesia * Surgical unexpected complications requiring strong haemodynamic support (transfusions, vasopressors, inotropes) **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients scheduled for elective abdominal surgery by laparotomy (general surgery or gynaecological surgery) who will receive a thoracic epidural (around T9-T10/T10-T11) and general anesthesia. ### Contacts Locations Module #### Locations **Location 1:** **City:** Montreal **Country:** Canada **Facility:** Hôpital Maisonneuve-Rosemont **State:** Quebec #### Overall Officials **Official 1:** **Affiliation:** Maisonneuve-Rosemont Hospital **Name:** Philippe Richebé, M.D. PhD **Role:** PRINCIPAL_INVESTIGATOR ## 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: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M1696 - Name: Remifentanil - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00913679 **Brief Title:** A Comparison of Two Different Surgical Techniques in Hip Resurfacing Arthroplasty **Official Title:** A Comparison of Two Different Surgical Techniques to Preserve the Bony Supply and Improve Implant Longevity in Hip Resurfacing Arthroplasty #### Organization Study ID Info **ID:** 20070082 #### Organization **Class:** OTHER **Full Name:** University of Aarhus ### Status Module #### Completion Date **Date:** 2020-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-12-15 **Type:** ACTUAL **Last Update Submit Date:** 2022-12-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-02-20 **Type:** ACTUAL #### Start Date **Date:** 2008-11-01 **Type:** ACTUAL **Status Verified Date:** 2022-12 #### Study First Post Date **Date:** 2009-06-04 **Type:** ESTIMATED **Study First Submit Date:** 2009-06-02 **Study First Submit QC Date:** 2009-06-03 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Aarhus University Hospital **Class:** INDUSTRY **Name:** Zimmer Biomet #### Lead Sponsor **Class:** OTHER **Name:** University of Aarhus #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of the study is to compare two different surgical techniques in hip resurfacing arthroplasty (RHA), comparing bloodflow and metabolism in the femoral head, as well as implant migration, periprosthetic bone mineral density, gait function and patient recovery. **Detailed Description:** BACKGROUND: 6700 total hip replacements are performed each year in Denmark due to osteoarthritis. Young patients sustain a substantial risk of early implant failure due to high-activity daily living, and among patients younger than 55 years at surgery 20 percent need revision surgery within ten years. Revision surgery is more complicated than primary surgery and associated with decreased implant longevity due to decreased bone stock. Resurfacing hip arthroplasty (RHA), restores the anatomy of the hip as only the articulating joint surfaces are replaced, and thus more bone is left to ensure a better opportunity of successful revision surgery later on. The clinical midterm evaluation of RHA survival is promising, but two major complications leading to early revision, namely osteonecrosis and femoral neck fracture, has raised concern regarding the influence of surgical technique on the vascularity of the femoral head. RHA is commonly performed through a posterolateral surgical approach. By this technique muscle tendons are spilt resulting in decreased patient mobility for several weeks after surgery, but more importantly, the blood supply is compromised as a large artery has to be ligated. This is speculated to decrease the blood supply to femoral head and neck and thereby increase the risk of osteonecrosis, femoral neck fracture, and implant failure. With a new surgical technique facilitating an anterolateral approach to the hip joint the blood supply is left intact as well as the muscle tendons. HYPOTHESIS: An anterolateral surgical approach in resurfacing hip arthroplasty will 1) preserve the blood supply to the femoral head and neck and improve implant longevity, and 2) spare the muscle tendons and ease patient recovery. METHOD and FACILITIES: 50 patients, aged 30 to 60 years, with osteoarthrosis of the hip will be randomised to a RHA inserted by either an anterolateral or a posterolateral surgical approach. Primary points of evaluation are 1) blood supply to the femoral head and neck measured intraoperatively by Laser Doppler flowmetry and postoperatively by microdialysis established during surgery. Secondary points of evaluation are 1) implant fixation measured by radiostereometric analysis (RSA), and 2) periprosthetic bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DEXA), 3) gait analysis and 4) clinical scores of function, pain and activities of daily living (Harris Hip Score , Visual Analogue Scale). ### Conditions Module **Conditions:** - Osteonecrosis - Femoral Neck Fracture - Implant Failure **Keywords:** - osteonecrosis - femoral neck fracture - implant fixation - implant failure - periprosthetic bone mineral density - gait function - gait analysis - patient recovery ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 49 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Posterior surgical approach in hip resurfacing arthroplasty **Intervention Names:** - Procedure: Surgical approach (ReCap Hip Resurfacing System) **Label:** Posterior approach **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Anterolateral surgical approach in hip resurfacing arthroplasty **Intervention Names:** - Procedure: Surgical approach (ReCap Hip Resurfacing System) **Label:** Anterolateral approach **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Anterolateral approach - Posterior approach **Description:** two different surgical approaches in hip resurfacing arthroplasty **Name:** Surgical approach (ReCap Hip Resurfacing System) **Other Names:** - ReCap Hip Resurfacing System **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** femoral head blood flow, evaluated by Laser Doppler Flowmetry **Time Frame:** during surgery **Measure:** femoral head metabolism, evaluated by microdialysis **Time Frame:** 3 days #### Secondary Outcomes **Measure:** implant fixation, evaluated by RSA (radiostereogrammetric analysis) **Time Frame:** postoperatively; 3 months; 1,2 and 5 years **Measure:** periprosthetic bone mineral density, evaluated by DEXA **Time Frame:** pre- and postoperatively; 1 and 2 years **Measure:** gait function, evaluated by gait analysis **Time Frame:** preoperatively; 3 months and 1 year **Measure:** patient recovery, evaluated by Harris Hip Score and Visual Analogue Scale **Time Frame:** preoperatively and 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Primary hip OA; * Secondary hip OA due to mild and moderate acetabular dysplasia; * Sufficient bone quality for cementless acetabular component; * Suited for resurfacing of the femoral head, pre and intraoperatively assessed; * Age 30 to 60 years. Exclusion Criteria: * Neuromuscular or vascular diseases in affected leg; * Patients found intra-operatively to be unsuited for a cementless acetabular component or cementing of the femoral component; * Need of NSAID postoperatively; * Fracture sequelae; * Females at risk of pregnancy, no safe contraceptives; * Severe hip dysplasia; * Sequelae from hip disease in childhood; * Medicine with large effect on bone density, K vitamin antagonists, loop-diuretics; * Alcoholism, females over 14 units per week, males over 21 units per week; AVN; * Osteoporosis. **Maximum Age:** 60 Years **Minimum Age:** 30 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Aarhus C **Country:** Denmark **Facility:** Aarhus University Hospital, Department of Orthopaedic Surgery, Tage-Hansens Gade 2 **State:** Aarhus County **Zip:** 8000 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000050723 - Term: Fractures, Bone - ID: D000014947 - Term: Wounds and Injuries - ID: D000006620 - Term: Hip Fractures - ID: D000005264 - Term: Femoral Fractures - ID: D000025981 - Term: Hip Injuries - ID: D000007869 - Term: Leg Injuries - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000009336 - Term: Necrosis - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M8403 - Name: Femoral Neck Fractures - Relevance: HIGH - As Found: Femoral Neck Fractures - ID: M26370 - Name: Fractures, Bone - Relevance: LOW - As Found: Unknown - ID: M12943 - Name: Osteonecrosis - Relevance: HIGH - As Found: Osteonecrosis - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M9696 - Name: Hip Fractures - Relevance: LOW - As Found: Unknown - ID: M8402 - Name: Femoral Fractures - Relevance: LOW - As Found: Unknown - ID: M23105 - Name: Hip Injuries - Relevance: LOW - As Found: Unknown - ID: M10881 - Name: Leg Injuries - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M12284 - Name: Necrosis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010020 - Term: Osteonecrosis - ID: D000005265 - Term: Femoral Neck Fractures ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03399279 **Brief Title:** Perforated Collagen Membrane With Nanohydroxyapatite for Intrabony Defects **Official Title:** Comparative Study Of Perforated Versus Non Perforated Collagen Membrane Combined With Nanohydroxyapatite In The Management Of Intrabony Defects #### Organization Study ID Info **ID:** 0925-0586 #### Organization **Class:** OTHER **Full Name:** Ain Shams University ### Status Module #### Completion Date **Date:** 2017-03-25 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-01-17 **Type:** ACTUAL **Last Update Submit Date:** 2018-01-13 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-09-15 **Type:** ACTUAL #### Start Date **Date:** 2014-12-17 **Type:** ACTUAL **Status Verified Date:** 2018-01 #### Study First Post Date **Date:** 2018-01-16 **Type:** ACTUAL **Study First Submit Date:** 2018-01-08 **Study First Submit QC Date:** 2018-01-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ain Shams University #### Responsible Party **Investigator Affiliation:** Ain Shams University **Investigator Full Name:** Hesham Mohammed Abdallah **Investigator Title:** Dr. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The ultimate goal of periodontal therapy is the regeneration of periodontal tissues which have been destroyed due to periodontal disease. Different modalities have been proposed to obtain regeneration of periodontal tissues employing various bone grafts, bone substitute materials, guided tissue regeneration (GTR), combination of bone grafts or bone substitutes with GTR, and growth factors. So, a new, fully synthetic, nanocrystalline, unsintered, phase-pure hydroxyapatite (nano-HA) has been suggested as a potential material for enhancing periodontal and bone regeneration since its chemical composition and crystalline structure correspond to the calcium phosphate component of natural bone and may have greater potential for resorption compared with sintered hydroxyapatite. A study performed in 2012, on 14 patients with paired intrabony periodontal defects of ≥4 mm participated in split mouth design study. The defects in each subject were randomly selected to receive nano-HA paste in conjunction with papilla preservation flaps or papilla preservation flaps alone. Probing bone levels from a customized acrylic stent and probing pocket depths were measured at baseline and again 6 months following surgery. No differences in any of the investigated parameters were observed at baseline between the two groups. Healing was uneventful in all patients. Both treatments resulted in significant improvements between baseline and 6 months in all clinical and radio-graphic parameters. In conclusion, they found that the nano crystalline hydroxyapatite bone graft in combination with collagen membrane demonstrated clinical advantages beyond that achieved by open flap debridement alone. The concept of porous guided tissue membrane has been tested recently as a modality that could stimulate bone formation of critical sized bone defects. Kim and co-workers claimed that asymmetrically porous GBR membranes with dual BMP-2 and ultrasound stimulation may be promising for the clinical treatment of delayed and insufficient bone healing. For guided tissue regeneration in periodontal therapy, membrane perforations could allow for gingival stem cells and periosteal cells to take part in supracrestal regeneration. The perforated section of the membranes would stabilize supracrestal fibrin clot through mechanical interlocking of fibrin strands with the membrane pores providing more membrane and clot stability. It has been suggested that regenerative failures may result when the tensile strength of the fibrin clot is exceeded, resulting in a tear and a long junctional epithelium type attachment. **Detailed Description:** The study will be conducted on 12 individuals. The research esthetics committee of Faculty of Dentistry, Ain Shams University will review the proposal. All patients will be informed about the nature of the study and will fine an informed consent. I - Selection of the patients: The patients will be selected from the outpatient clinic of Oral Medicine and Periodontology department, Faculty of Dentistry, Ain Shams University. All the selected patients will be selected according to following criteria: Inclusion criteria: 1. Patients free from any systemic diseases as evidenced by health using Burket's Oral Medicine health history questionnaire. (Glick, 2008) 2. Patients' age range from 25 to 50 years old. 3. Each patient should have at least two contralateral intrabony defects which fulfill the following criteria: (i) Probing depth ≥ 5 mm. (ii) Clinical attachment loss ≥ 5 mm. (iii) Radiographic evidence of vertical bone loss using periapical radiographs. 4. Patients are should be willing to participate in the study and should be able to return for the follow up visits. Exclusion criteria: 1. Patients with history of periodontal surgery or medications including antibiotics and non-steroidal anti-inflammatory drugs for at least 3 months prior to the initiation of the study. 2. Pregnant females as well as breast feeding mothers. 3. Smokers. 4. Vulnerable groups as prisoners, mentally disabled, etc... All participants following initial clinical examination and periapical radiographs will be given detailed instructions in self-performed plaque control measures, including tooth brushing and dental flossing. All patients will receive full mouth scaling and root planing using ultra-sonic scalers and hand instruments under local anesthesia to minimize patient discomfort. II- Study groups: The selected sites will be randomly "double blinded study" divided into two groups in a split mouth design. Group One: The defects will be treated with open flap debridment followed by the placement of nanohydroxyapetite\* combined with perforated collagen membrane\*\*. Group Two: The defects will be treated with open flap debridment followed by the placement of nanohydroxyapetite combined with non perforated collagen membrane. The mucoperiosteal flaps will be adapted and sutured and the patients will be given post-surgical instructions. III- Periodontal evaluation: Clinical Parameters: The clinical parameters will be measured at one, three and six months postoperatively. 1) Plaque index (PI): Criteria of plaque index (PI) of (Silness and Loe, 1969) 0: No plaque in gingival area. 1. No plaque visible by the unaided eye, but plaque is made visible on the point of the probe after it has been moved across surface at entrance of gingival crevice. 2. Gingival area is covered with thin to moderately thick layer of plaque, deposit is visible to naked eye. 3. Heavy accumulation of plaque, the thickness of which fills out niche produced by gingival margin and tooth surface, inter dental area is stuffed with plaque. 2) Gingival index (GI): Criteria of the gingival index (GI) of (Loe, 1967) 0: Normal gingiva 1. Mild inflammation: slight change in color and slight edema; no bleeding on probing. 2. moderate inflammation: redness, edema and glazing; bleeding on probing. 3. Severe inflammation: marked redness and edema; ulceration; tendency to spontaneous bleeding. 3) Probing pocket depth (PPD) : Probing pocket depth (PPD) will be measured from the gingival margin to the base of periodontal pocket to the nearest mm (Caton, 1989). Six readings will be recorded for each tooth: Mesiobuccal, mid-buccal, distobuccal, mesiolingual, mid-lingual and distolingual. 4) Clinical attachment level (CAL): Clinical attachment level will be measured from cementoenamel junction to the base of pocket to the nearest mm. B- Radiographic parameters Periapical radiographs and Cone beam computed tomography will be taken at base line and at six months after the placement of barrier membranes combined with nanohydroxyapatite and the following parameters will be measured: The sites will be measured first on periapical radiographs and later on CBCT with the help of the ruler in the Image Tool software (University of Texas Health Science Centre, San Antonio, TX) based on the method proposed by Misch et al. Three measurements will be performed for each site: 1. The height of the alveolar crest (AC): measured from the cementoenamel junction (CEJ) to the AC. 2. The depth of the defect, measured from the CEJ to the bottom of the defect. 3. The width of the defect, measured from the highest point of the AC to the dental root adjacent to the defect. The axial slices will be used to verify the presence of combined bone defects and identify according to the classification of Goldman and Cohen. ### Conditions Module **Conditions:** - Intrabony Periodontal Defect **Keywords:** - nanohydroxyapatite - Perforated membrane - occlusive membrane - Aggressive periodontitis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 18 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Perforated collagen membrane and nano-hydroxyapatite and open flap debridement **Intervention Names:** - Procedure: Open flap debridment - Other: Perforated collagen membrane - Other: Nanohydroxyapetite **Label:** Open flap debridement & perforated&Nano **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Occlusive membrane and nano-hydroxyapatite and open flap debridement **Intervention Names:** - Procedure: Open flap debridment - Other: Occlusive membrane - Other: Nanohydroxyapetite **Label:** Open flap debridment &Occlusive&Nano **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Open flap debridement & perforated&Nano - Open flap debridment &Occlusive&Nano **Description:** Full mucoperiosteal flap reflected+ Debridement of infrabony defect **Name:** Open flap debridment **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Open flap debridement & perforated&Nano **Description:** Membrane perforations using dental needle **Name:** Perforated collagen membrane **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Open flap debridment &Occlusive&Nano **Description:** Biotech collagen membrane **Name:** Occlusive membrane **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Open flap debridement & perforated&Nano - Open flap debridment &Occlusive&Nano **Description:** Nanbone Particles **Name:** Nanohydroxyapetite **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Clinical attachment level **Measure:** CAL **Time Frame:** Change from base line to 3 months and 6 months #### Secondary Outcomes **Description:** Depth of Defect (From cemento enamel junction to defect base) **Measure:** DOD **Time Frame:** Change from base line to 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients free from any systemic diseases as evidenced by health using Burket's Oral Medicine health history questionnaire. (Glick, 2008) * Patients' age range from 25 to 50 years old. * Each patient should have at least two contralateral intrabony defects which fulfill the following criteria: \*\* Probing depth ≥ 5 mm. * Clinical attachment loss ≥ 5 mm. * Radiographic evidence of vertical bone loss using periapical radiographs. * Patients are should be willing to participate in the study and should be able to return for the follow up visits. Exclusion Criteria: * Patients with history of periodontal surgery or medications including antibiotics and non-steroidal anti-inflammatory drugs for at least 3 months prior to the initiation of the study. * Pregnant females as well as breast feeding mothers. * Smokers. * Vulnerable groups as prisoners, mentally disabled, etc... **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 25 Years **Sex:** ALL **Standard Ages:** - ADULT ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M13427 - Name: Periodontitis - Relevance: LOW - As Found: Unknown - ID: M3724 - Name: Aggression - Relevance: LOW - As Found: Unknown - ID: M13429 - Name: Aggressive Periodontitis - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04391179 **Acronym:** DICER **Brief Title:** Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19 **Official Title:** Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19 #### Organization Study ID Info **ID:** HUM00179783 #### Organization **Class:** OTHER **Full Name:** University of Michigan ### Status Module #### Completion Date **Date:** 2021-02-22 **Type:** ACTUAL #### Last Update Post Date **Date:** 2022-03-24 **Type:** ACTUAL **Last Update Submit Date:** 2022-03-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-02-22 **Type:** ACTUAL #### Results First Post Date **Date:** 2022-03-24 **Type:** ACTUAL **Results First Submit Date:** 2022-03-04 **Results First Submit QC Date:** 2022-03-18 #### Start Date **Date:** 2020-05-31 **Type:** ACTUAL **Status Verified Date:** 2022-03 #### Study First Post Date **Date:** 2020-05-18 **Type:** ACTUAL **Study First Submit Date:** 2020-05-15 **Study First Submit QC Date:** 2020-05-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Michigan #### Responsible Party **Investigator Affiliation:** University of Michigan **Investigator Full Name:** Jason Scott Knight **Investigator Title:** Associate Professor of Internal Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The most severe manifestations of COVID-19 include respiratory failure, coagulation problems, and death. Inflammation and blood clotting are believed to play an important role in these manifestations. Research in humans has shown that dipyridamole can reduce blood clotting. This research study is being conducted to learn whether 14 days of treatment with dipyridamole will reduce excessive blood clotting in COVID-19. This study will enroll participants with confirmed coronavirus (SARS-CoV)-2 infection that are admitted. Eligible participants will be randomized to receive dipyridamole or placebo for 14 days in the hospital. In addition, data will be collected from the medical record, and there will also be blood draws during the hospitalization. ### Conditions Module **Conditions:** - COVID - Corona Virus Infection - Covid-19 - SARS-CoV-2 Infection **Keywords:** - Oxygen ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 99 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) **Intervention Names:** - Drug: Dipyridamole 100 Milligram(mg) **Label:** Dipyridamole 100 Milligram(mg) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo given by mouth four times a day **Intervention Names:** - Drug: Placebo oral tablet **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Dipyridamole 100 Milligram(mg) **Description:** Drug will be given for 14 days while in the hospital. **Name:** Dipyridamole 100 Milligram(mg) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo will be given for 14 days while in the hospital. **Name:** Placebo oral tablet **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** average percent daily change in plasma D-dimer levels compared to baseline **Measure:** Percent Change in D-dimer **Time Frame:** baseline, up to approximately 14 days after last study drug administration **Description:** Compare each dipyridamole patient head to head against each placebo patient using a hierarchical composite rank score 1. death 2. days on mechanical ventilation 3. dichotomized (yes/no) decrease in daily average SpO2/FiO2 of at least 50 units relative to day 1 at anytime during the observation period 4. cumulative sum of COVID ordinal score during study hospitalization. Ordinal scores could range 1-8. Levels 1 and 2 imply no hospitalization and 8 is the worst possible score (death); by definition, the subjects in the DICER study were hospitalized during the time period in which the study observed their ordinal scores. **Measure:** Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score **Time Frame:** up to approximately 30 days after hospital discharge #### Secondary Outcomes **Description:** Organ support is defined as receipt of invasive mechanical ventilation, vasopressor therapy, ECMO support, or dialysis. **Measure:** Days Alive and Free of Organ Support **Time Frame:** up to approximately 28 days after last study drug administration score **Description:** Death of any cause during duration of study participation **Measure:** Individual Component of Composite Endpoint- Death **Time Frame:** up to approximately 30 days after hospital discharge **Description:** The number of days spent on invasive mechanical ventilation during study hospitalization. **Measure:** Individual Component of Composite Endpoint- Days on Mechanical Ventilation **Time Frame:** up to 14 days after study drug administration **Description:** Binary outcome indicating patients whose Sp02/Fi02 dropped 50 points relative to baseline at any time during hospitalization. **Measure:** Individual Component of Composite Endpoint- Sp02/Fi02 (as Shown by Participant Count) **Time Frame:** up to 14 days after study drug administration **Description:** Cumulative sum of WHO Ordinal Scale for Clinical Improvement scores during hospitalization or through 14 days after study drug administration, whichever occurs first. The WHO Ordinal Scale ranges from 1 (no limitation of activities) through 8 (death). By definition, hospitalized patients score 3 or higher on the scale. The equation can be written: Cumulative Ordinal Score = (days in hospital up to 14) x (average ordinal score during hospitalization). Higher scores represent a combination of worse outcomes and longer hospitalizations. **Measure:** Individual Component of Composite Endpoint- Cumulative Ordinal Score **Time Frame:** Hospitalization up to 14 days after study drug administration ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Willing and able to provide informed consent prior to performing study procedures unless they have a legally authorized representative (LAR) * Confirmed coronavirus (SARS-CoV-2) infection * Currently hospitalized or anticipated hospitalization requiring supplemental oxygen Exclusion Criteria: * In the opinion of at least two investigators, unlikely to survive for \>48 hours from screening * Concurrent enrollment in a clinical trial with a cytokine inhibitor (targeting interleukin-6 (IL-6), Interleukin-6 Receptor (IL-6R), IL-1, or Janus kinase). Use of remdesivir is permitted. * Currently on invasive mechanical ventilation. * Hypotension defined as systolic blood pressure \< 90 mmHg on two sequential readings at least 4 hours apart * Pregnant or breastfeeding * Concurrent dual antithrombotic therapy (aspirin or P2Y12 inhibitor plus anticoagulation to treat deep venous thrombosis or pulmonary embolism (single antiplatelet or anticoagulant agent at prophylaxis or therapeutic dose is permitted) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 times upper limit of normal, hemoglobin \< 8 grams per deciliter (g/dL), or platelets \<50,000 per cubic millimeter (mm3) * History of recent major bleeding, defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis (ISTH). * Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study **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:** Jason Knight, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2021-07-12 - Filename: Prot_002.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1336010 - Type Abbrev: Prot - Upload Date: 2022-03-10T14:42 - Date: 2022-02-03 - Filename: SAP_003.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 709870 - Type Abbrev: SAP - Upload Date: 2022-03-10T14:44 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000014777 - Term: Virus Diseases - 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: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: HIGH - As Found: Corona Virus Infection - ID: M22700 - Name: Disease Attributes - 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: M14978 - Name: Respiratory Tract 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: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000086382 - Term: COVID-19 - ID: D000018352 - Term: Coronavirus Infections ### 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: D000014665 - Term: Vasodilator Agents ### 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: M7358 - Name: Dipyridamole - Relevance: HIGH - As Found: Positive control - 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: M17412 - Name: Vasodilator Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000004176 - Term: Dipyridamole ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2022-03-11 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Dipyridamole 100 Milligram(mg) **Deaths Num At Risk:** 49 **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** EG000 **Other Num Affected:** 43 **Other Num at Risk:** 49 **Serious Number Affected:** 14 **Serious Number At Risk:** 49 **Title:** Dipyridamole 100 Milligram(mg) **Group ID:** EG001 **Title:** Placebo **Deaths Num Affected:** 3 **Deaths Num At Risk:** 50 **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** EG001 **Other Num Affected:** 15 **Other Num at Risk:** 50 **Serious Number Affected:** 30 **Serious Number At Risk:** 50 **Title:** Placebo **Frequency Threshold:** 0 #### Other Events **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Delirium **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Paresthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Bradycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Heart failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Ventricular arrhythmia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Electrocardiogram QT corrected interval prolonged **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Palpitations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Edema limbs **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Kidney infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Atypical urothelial cells in urine **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Incontinence **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Diarrhea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Emesis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Vaginal hemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Rash maculo-papular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Neck pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Ankle pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Body pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Diaphoresis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Tremor **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) #### Serious Events **Term:** Atrial Fibrillation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Delirium **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 49 **Group ID:** EG001 **Num At Risk:** 50 **Term:** Respiratory failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 7 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 14 **Num At Risk:** 50 **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 50 **Term:** Heart failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 49 **Group ID:** EG001 **Num At Risk:** 50 **Term:** Lung infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 50 **Term:** Pulmonary edema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 49 **Group ID:** EG001 **Num At Risk:** 50 **Term:** Thromboembolic event **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Cardiac Arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Paroxysmal artrial tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Pneumothorax **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Stroke **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 49 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 50 **Time Frame:** The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 49 **Group ID:** BG001 **Value:** 50 **Group ID:** BG002 **Value:** 99 **Units:** Participants ### Group **ID:** BG000 **Title:** Dipyridamole 100 Milligram(mg) **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. ### Group **ID:** BG001 **Title:** Placebo **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. ### 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:** 31 #### Measurement **Group ID:** BG001 **Value:** 29 #### Measurement **Group ID:** BG002 **Value:** 60 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 18 #### Measurement **Group ID:** BG001 **Value:** 21 #### Measurement **Group ID:** BG002 **Value:** 39 **Category Title:** >=65 years #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 49 **Group ID:** BG001 **Value:** 50 **Group ID:** BG002 **Value:** 99 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 16 #### Measurement **Group ID:** BG001 **Value:** 17 #### Measurement **Group ID:** BG002 **Value:** 33 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 33 #### Measurement **Group ID:** BG001 **Value:** 33 #### Measurement **Group ID:** BG002 **Value:** 66 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 49 **Group ID:** BG001 **Value:** 50 **Group ID:** BG002 **Value:** 99 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 46 #### Measurement **Group ID:** BG001 **Value:** 48 #### Measurement **Group ID:** BG002 **Value:** 94 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 49 **Group ID:** BG001 **Value:** 50 **Group ID:** BG002 **Value:** 99 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 45 #### Measurement **Group ID:** BG001 **Value:** 42 #### Measurement **Group ID:** BG002 **Value:** 87 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 49 **Group ID:** BG001 **Value:** 50 **Group ID:** BG002 **Value:** 99 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** .80 **Value:** 1.06 #### Measurement **Group ID:** BG001 **Spread:** 1.46 **Value:** 1.24 #### Measurement **Group ID:** BG002 **Spread:** 1.18 **Value:** 1.15 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 47 **Group ID:** BG001 **Value:** 49 **Group ID:** BG002 **Value:** 96 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 70 **Value:** 308 #### Measurement **Group ID:** BG001 **Spread:** 72 **Value:** 310 #### Measurement **Group ID:** BG002 **Spread:** 71 **Value:** 309 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 49 **Group ID:** BG001 **Value:** 50 **Group ID:** BG002 **Value:** 99 **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 **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:** Baseline plasma D-dimer level **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Three patients did not have baseline D-Dimer values on the day of study drug. **Title:** D-Dimer **Unit of Measure:** mg/L ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) **Unit of Measure:** ratio ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** University of Michigan **Phone:** 734-763-3031 **Title:** Jason Knight, MD, PhD ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -.089 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** .023 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** .027 **Estimate Comment:** Estimation represents log-scale difference between average daily change in D-Dimer for Dipyridamole patients minus placebo average daily change. Negative estimates indicate that D-Dimer levels decline faster in Dipyridamole versus placebo patients. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.24 **P-Value Comment:** **Parameter Type:** Slope **Parameter Value:** -.033 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 0.78 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.8 **CI Upper Limit:** 1.29 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** win ratio= (the probability of a win for the dipyridamole patient)/(probability of a win for the placebo patient) **Group Description:** A win ratio analysis of the hierarchical composite outcome requiring direct comparison of outcomes between each dipyridamole patient and placebo patient. The patient with the superior outcome is adjudicated the 'winner' and receives a +1 score, while the 'loser' scores -1. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** .98 **P-Value Comment:** **Parameter Type:** win ratio **Parameter Value:** 1.00 **Statistical Comment:** **Statistical Method:** Mantel Haenszel **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** .08 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Wilcoxon (Mann-Whitney) **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** .09 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** 0.02 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.94 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** estimated ratio of days on mechanical ventilation for dipyridamole and placebo **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.36 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** 0.29 **Statistical Comment:** **Statistical Method:** regression, negative binomial **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** 0.43 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.51 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Odds of a 50 point drop in the dipyridamole group relative to the placebo group. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** .94 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.04 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** .95 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Wilcoxon (Mann-Whitney) **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -10.2 - **Spread:** - **Upper Limit:** -0.07 - **Value:** -5.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -6.9 - **Spread:** - **Upper Limit:** 2.3 - **Value:** -2.4 **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:** 3 **Title:** Composite endpoint- death ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** Composite endpoint- mechanical ventilation during hospitalization ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** Composite endpoint- 50+ unit drop SpO2/FiO2 ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32 **Title:** Composite endpoint- remaining (ties among patients evaluated by ordinal score) #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 28 - **Spread:** - **Upper Limit:** 28 - **Value:** 28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 28 - **Spread:** - **Upper Limit:** 28 - **Value:** 28 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.36 - **Upper Limit:** - **Value:** 0.33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.74 - **Upper Limit:** - **Value:** 0.88 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 9.4 - **Spread:** - **Upper Limit:** 21.4 - **Value:** 14.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.8 - **Spread:** - **Upper Limit:** 30.0 - **Value:** 15.0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** average percent daily change in plasma D-dimer levels compared to baseline **Dispersion Type:** 97.8% Confidence Interval **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** baseline, up to approximately 14 days after last study drug administration **Title:** Percent Change in D-dimer **Type:** PRIMARY **Unit of Measure:** percent daily change ##### Group **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** OG000 **Title:** Dipyridamole 100 Milligram(mg) ##### Group **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** OG001 **Title:** Placebo #### Outcome Measure 2 **Description:** Compare each dipyridamole patient head to head against each placebo patient using a hierarchical composite rank score 1. death 2. days on mechanical ventilation 3. dichotomized (yes/no) decrease in daily average SpO2/FiO2 of at least 50 units relative to day 1 at anytime during the observation period 4. cumulative sum of COVID ordinal score during study hospitalization. Ordinal scores could range 1-8. Levels 1 and 2 imply no hospitalization and 8 is the worst possible score (death); by definition, the subjects in the DICER study were hospitalized during the time period in which the study observed their ordinal scores. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** up to approximately 30 days after hospital discharge **Title:** Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** OG000 **Title:** Dipyridamole 100 Milligram(mg) ##### Group **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** OG001 **Title:** Placebo #### Outcome Measure 3 **Description:** Organ support is defined as receipt of invasive mechanical ventilation, vasopressor therapy, ECMO support, or dialysis. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** 5 participants on dipyridamole and 2 participants on placebo were excluded from this analysis because of their early withdrawal from the study (prior to 28 days after last study drug administration). **Reporting Status:** POSTED **Time Frame:** up to approximately 28 days after last study drug administration score **Title:** Days Alive and Free of Organ Support **Type:** SECONDARY **Unit of Measure:** days ##### Group **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** OG000 **Title:** Dipyridamole 100 Milligram(mg) ##### Group **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** OG001 **Title:** Placebo #### Outcome Measure 4 **Description:** Death of any cause during duration of study participation **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** up to approximately 30 days after hospital discharge **Title:** Individual Component of Composite Endpoint- Death **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** OG000 **Title:** Dipyridamole 100 Milligram(mg) ##### Group **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** OG001 **Title:** Placebo #### Outcome Measure 5 **Description:** The number of days spent on invasive mechanical ventilation during study hospitalization. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** up to 14 days after study drug administration **Title:** Individual Component of Composite Endpoint- Days on Mechanical Ventilation **Type:** SECONDARY **Unit of Measure:** days ##### Group **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** OG000 **Title:** Dipyridamole 100 Milligram(mg) ##### Group **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** OG001 **Title:** Placebo #### Outcome Measure 6 **Description:** Binary outcome indicating patients whose Sp02/Fi02 dropped 50 points relative to baseline at any time during hospitalization. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** up to 14 days after study drug administration **Title:** Individual Component of Composite Endpoint- Sp02/Fi02 (as Shown by Participant Count) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** OG000 **Title:** Dipyridamole 100 Milligram(mg) ##### Group **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** OG001 **Title:** Placebo #### Outcome Measure 7 **Description:** Cumulative sum of WHO Ordinal Scale for Clinical Improvement scores during hospitalization or through 14 days after study drug administration, whichever occurs first. The WHO Ordinal Scale ranges from 1 (no limitation of activities) through 8 (death). By definition, hospitalized patients score 3 or higher on the scale. The equation can be written: Cumulative Ordinal Score = (days in hospital up to 14) x (average ordinal score during hospitalization). Higher scores represent a combination of worse outcomes and longer hospitalizations. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** excluded patients that died or withdrew from the study **Reporting Status:** POSTED **Time Frame:** Hospitalization up to 14 days after study drug administration **Title:** Individual Component of Composite Endpoint- Cumulative Ordinal Score **Type:** SECONDARY **Unit of Measure:** score on a scale * days ##### Group **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** OG000 **Title:** Dipyridamole 100 Milligram(mg) ##### Group **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** OG001 **Title:** Placebo ### Participant Flow Module #### Group **Description:** 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital. **ID:** FG000 **Title:** Dipyridamole 100 Milligram(mg) #### Group **Description:** Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital. **ID:** FG001 **Title:** Placebo #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 49 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 50 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 34 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 34 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 15 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 16 **Recruitment Details:** Between May 2020 and January 2021, 99 eligible participants received at least one dose of study drug and were included in the analysis. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT06165679 **Brief Title:** Effect of Prilocaine vs Bupivacaine on Hemodynamics in Spinal Anesthesia for Geriatric Patients **Official Title:** Comparison Between the Effect of Prilocaine vs Bupivacaine on Hemodynamics in Spinal Anesthesia for Geriatric Patients Undergoing Endoscopic Urological Surgeries: A Randomized Controlled Trial #### Organization Study ID Info **ID:** N-439-2023 #### Organization **Class:** OTHER **Full Name:** Cairo University ### Status Module #### Completion Date **Date:** 2024-07-15 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-12 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-11 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-06-15 **Type:** ESTIMATED #### Start Date **Date:** 2023-12-20 **Type:** ACTUAL **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2023-12-11 **Type:** ACTUAL **Study First Submit Date:** 2023-12-02 **Study First Submit QC Date:** 2023-12-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cairo University #### Responsible Party **Investigator Affiliation:** Cairo University **Investigator Full Name:** AbdElKhalik Mahmoud Shaban **Investigator Title:** Lecturer of anaesthesia **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Data comparing prilocaine vs bupivacaine in equipotent doses in the elderly are lacking; therefore, the study will compare the effect of prilocaine vs bupivacaine on hemodynamics in spinal anesthesia for geriatric patients undergoing endoscopic urological surgeries ### Conditions Module **Conditions:** - Hemodynamic Instability ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 112 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Prilocaine **Label:** Prilocaine group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Intervention Names:** - Drug: Bupivacaine **Label:** Bupivacaine GROUP **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Prilocaine group **Description:** The patients will receive a single injection of spinal anesthesia using prilocaine plus fentanyl **Name:** Prilocaine **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Bupivacaine GROUP **Description:** The patients will receive a single injection of spinal anesthesia using Bupivacaine plus fentanyl **Name:** Bupivacaine **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Mean and systolic arterial blood pressure values after spinal anesthesia **Measure:** Mean and systolic arterial blood pressure values **Time Frame:** Until the patient will have no lower limbs motor weakness assessed up to 6 hours after spinal anesthesia **Description:** Heart rate after spinal anesthesia **Measure:** Heart rate **Time Frame:** Until the patient will have no lower limbs motor weakness assessed up to 6 hours after spinal anesthesia #### Primary Outcomes **Description:** Incidence of hypotension from local anesthetic injection **Measure:** Hypotension **Time Frame:** Till 30 minutes after spinal anesthesia. #### Secondary Outcomes **Description:** Total doses of vasopressor drugs used for hypotension treatment **Measure:** Use of vasopressor drugs **Time Frame:** Until the patient will have no lower limbs motor weakness assessed up to 6 hours after spinal anesthesia ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients aged 65 years old and above. * Both genders. * Patients scheduled to undergo endoscopic urological surgeries. * ASA I and II class. Exclusion Criteria: * Patient refusal. * Known local anesthetic (LA) allergy. * Bleeding disorders. * Skin lesions or infections at site of needle insertion. * Hypertensive patients. * Patients candidate for transurethral resection of the prostate * ASA III and VI class **Minimum Age:** 65 Years **Sex:** ALL **Standard Ages:** - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Cairo **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** abdelkhalek m Samy - **Phone:** 01025854248 - **Role:** CONTACT ***Contact 2:*** - **Name:** Maged A AbdelAziz - **Role:** SUB_INVESTIGATOR ***Contact 3:*** - **Name:** Mohamed R Ahmed - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Mohamed A Morsy - **Role:** SUB_INVESTIGATOR **Country:** Egypt **Facility:** Kasr Alaini hospital **Status:** RECRUITING ## Derived Section ### 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 - Abbrev: AdjAn - Name: Adjuvants, Anesthesia - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M5315 - Name: Bupivacaine - Relevance: HIGH - As Found: Following - ID: M8418 - Name: Fentanyl - Relevance: LOW - As Found: Unknown - ID: M14191 - Name: Prilocaine - Relevance: HIGH - As Found: Weighted - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002045 - Term: Bupivacaine - ID: D000011318 - Term: Prilocaine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05851079 **Brief Title:** Accurate Screening and Prevention of Cervical Lesions-- Development of Accurate Screening Methods for Cervical Lesions **Official Title:** Accurate Screening and Prevention of Cervical Lesions-- Development of Accurate Screening Methods for Cervical Lesions #### Organization Study ID Info **ID:** IRB-20210333-R #### Organization **Class:** OTHER **Full Name:** Women's Hospital School Of Medicine Zhejiang University ### Status Module #### Completion Date **Date:** 2024-11-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-05-09 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-05 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-11-30 **Type:** ESTIMATED #### Start Date **Date:** 2021-12-10 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2023-05-09 **Type:** ACTUAL **Study First Submit Date:** 2023-04-24 **Study First Submit QC Date:** 2023-05-05 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Wuhan Central Hospital **Class:** OTHER **Name:** Tongji Hospital #### Lead Sponsor **Class:** OTHER **Name:** Women's Hospital School Of Medicine Zhejiang 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:** The goal of this observational study is to compare the accuracy and sensitivity of High-throughput human papilloma virus(HPV) typing and integrated assays with routine screening protocols (Cobas HPV test combined with thinprep cytologic test(TCT) for the detection of cervical intraepithelial neoplasia in the general and hospital populations. The main questions it aims to answer are: * High-throughput HPV typing and integrated assays can screen for ≥ cervical intraepithelial neoplasia (CIN2 or CIN3) with high sensitivity and accuracy. * High-throughput HPV typing and integrated assays can be promoted as a screening tool for cervical cancer. Participants will be screened with routine screening protocols (Cobas HPV test combined with TCT test), and if the results are abnormal, colposcopy and cervical biopsy will be performed. **Detailed Description:** 1. Stratified experimental design: Relying on the project's clinical multicenter to recruit patients for routine HPV screening in hospital outpatient clinics, for HPV high-risk type-positive subjects. The subjects with positive HPV types will continue to undergo TCT and colposcopic biopsy, and the remaining specimens after routine screening will be collected for high-throughput HPV typing and integrated assays. The sensitivity and accuracy of high-throughput HPV typing and integrated assays were compared with conventional screening methods. 2. Parallel experimental design: A multicenter cohort of 12,000 permanent residents was recruited for routine cervical cancer screening(HPV+TCT combined screening), and the remaining specimens were collected after the conventional screening to test the indexes of high-throughput HPV typing and integrated assays. The sensitivity and accuracy of high-throughput HPV typing and integrated assays were compared with conventional screening methods. 3. Prospective cohort study design: Based on a multicenter cohort of cervical cancer screening based on the project group, 3000 cervical cancer patients with HPV-positive routine screening and colposcopic biopsies were enrolled. The cohort was followed up regularly for 3 years with routine HPV+TCT and colposcopy, and cervical biopsy if necessary. And specimens remaining after routine screening will be collected for testing of high-throughput HPV typing and integrated assays. 4.subject selection: 1. .Stratified study design subjects were selected from patients who were first screened for cervical cancer in hospital outpatient clinics. 2. .Parallel trial design subjects were selected from resident female residents in a cohort of cervical cancer screening established by a clinical center. 3. .The prospective cohort study was designed to include HPV-positive patients in the cohort of cervical cancer screening established by the clinical center and whose cervical lesions were excluded by colposcopic biopsy. 5.This project is a multicenter prospective cohort study to investigate the immediate, 1st year, 2nd year and 3rd year cumulative risk of developing CIN2+ and CIN3+ in HPV 16 or 18-positive patients with positive and negative test results by integrating test results through a logistic Weibull model to assess whether colposcopy can be delayed and thus serve as a cervical cancer screening triage by comparing with risk values and clinical thresholds in the 2019 American Society for Colposcopy and Cervical Pathology(ASCCP)guidelines. ### Conditions Module **Conditions:** - Cervical Intraepithelial Neoplasia Grade 2/3 - Cervical Lesion **Keywords:** - Screening methods - Cervical Lesion - Sensitivity - Accuracy ### Design Module #### Bio Spec **Description:** Cervical exfoliated cells；Cervical biopsy **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 15000 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 3 Years ### Arms Interventions Module #### Arm Group 1 **Description:** Relying on the project's clinical multicenter to recruit patients for routine HPV screening in hospital outpatient clinics, for HPV high-risk type-positive subjects. The subjects with positive HPV types will continue to undergo TCT and colposcopic biopsy, and the remaining specimens after routine screening will be collected for high-throughput HPV typing and integrated assays. The sensitivity and accuracy of high-throughput HPV typing and integrated assays were compared with conventional screening methods. **Intervention Names:** - Diagnostic Test: TCT test - Diagnostic Test: Vaginoscopy - Diagnostic Test: High throughput HPV typing and integration detection methods - Diagnostic Test: Cobas HPV test **Label:** 1. Stratified experimental design #### Arm Group 2 **Description:** A multicenter cohort of 12,000 permanent residents was recruited for routine cervical cancer screening(HPV+TCT combined screening), and the remaining specimens were collected after the conventional screening to test the indexes of high-throughput HPV typing and integrated assays. The sensitivity and accuracy of high-throughput HPV typing and integrated assays were compared with conventional screening methods. **Intervention Names:** - Diagnostic Test: TCT test - Diagnostic Test: High throughput HPV typing and integration detection methods - Diagnostic Test: Cobas HPV test **Label:** 2. Parallel experimental design #### Arm Group 3 **Description:** Based on a multicenter cohort of cervical cancer screening based on the project group, 3000 cervical cancer patients with HPV-positive routine screening and colposcopic biopsies were enrolled. The cohort was followed up regularly for 3 years with routine HPV+TCT and colposcopy, and cervical biopsy if necessary. And specimens remaining after routine screening will be collected for testing of high-throughput HPV typing and integrated assays. **Intervention Names:** - Diagnostic Test: TCT test - Diagnostic Test: Vaginoscopy - Diagnostic Test: High throughput HPV typing and integration detection methods - Diagnostic Test: Cobas HPV test **Label:** 3. Prospective cohort study design: ### Interventions #### Intervention 1 **Arm Group Labels:** - 1. Stratified experimental design - 2. Parallel experimental design - 3. Prospective cohort study design: **Description:** These tests were performed on cervical exfoliated cells. **Name:** TCT test **Type:** DIAGNOSTIC_TEST #### Intervention 2 **Arm Group Labels:** - 1. Stratified experimental design - 3. Prospective cohort study design: **Description:** To obtain the results of the patient's pathology report. **Name:** Vaginoscopy **Type:** DIAGNOSTIC_TEST #### Intervention 3 **Arm Group Labels:** - 1. Stratified experimental design - 2. Parallel experimental design - 3. Prospective cohort study design: **Description:** This is screening for ≥ cervical intraepithelial tumors (CIN2 or CIN3). **Name:** High throughput HPV typing and integration detection methods **Type:** DIAGNOSTIC_TEST #### Intervention 4 **Arm Group Labels:** - 1. Stratified experimental design - 2. Parallel experimental design - 3. Prospective cohort study design: **Description:** To obtain HPV typing results. **Name:** Cobas HPV test **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Patients who meet the requirements for referral colposcopy were further examined for CIN2+ by pathology. **Measure:** the risk of cervical intraepithelial neoplasia(CIN) 2 or worse **Time Frame:** 3 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. First screening. 2. History of sexual intercourse. Exclusion Criteria: 1. Previous CIN, cervical cancer or other cervical lesions; 2. History of cervical treatment; 3. Age \<25, \>70 years; 4. Pregnancy. **Gender Based:** True **Gender Description:** Female **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 25 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Subjects were recruited in the general and hospital populations. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Hui Wang, PhD **Phone:** 0571-89998857 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Xiao Li, PhD **Phone:** 13958160137 **Role:** CONTACT #### Locations **Location 1:** **City:** Hangzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Hui Wang, PhD - **Phone:** 057189998857 - **Role:** CONTACT **Country:** China **Facility:** Women's hospital school of medicine zhejiang university **State:** Zhejiang **Status:** RECRUITING **Zip:** 310000 #### Overall Officials **Official 1:** **Affiliation:** Women's Hospital School Of Medicine Zhejiang University **Name:** Hui Wang, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000011230 - Term: Precancerous Conditions - 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: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M5826 - Name: Uterine Cervical Dysplasia - Relevance: HIGH - As Found: Cervical Intraepithelial Neoplasia - ID: M5825 - Name: Uterine Cervical Diseases - Relevance: HIGH - As Found: Cervical Lesions - ID: M14111 - Name: Precancerous Conditions - 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 - ID: T1074 - Name: Cervical Intraepithelial Neoplasia - Relevance: HIGH - As Found: Cervical Intraepithelial Neoplasia ### Condition Browse Module - Meshes - ID: D000002578 - Term: Uterine Cervical Dysplasia - ID: D000002577 - Term: Uterine Cervical Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01411579 **Brief Title:** Use of DwI-MR to Predict Chemotherapy Response of Liver Metastases and Hepatocarcinoma **Official Title:** Assessment of Diffusion-weighted Magnetic Resonance (MR) Imaging to Predict Chemotherapy Outcome in Liver Metastases and Hepatocellular Carcinoma (HCC) #### Organization Study ID Info **ID:** DWIPRECHEMOUT #### Organization **Class:** OTHER **Full Name:** University of Florence #### Secondary ID Infos **ID:** SIRM DWITALY ### Status Module #### Completion Date **Date:** 2013-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-12-10 **Type:** ESTIMATED **Last Update Submit Date:** 2014-12-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-02 **Type:** ACTUAL #### Start Date **Date:** 2011-02 **Status Verified Date:** 2014-12 #### Study First Post Date **Date:** 2011-08-08 **Type:** ESTIMATED **Study First Submit Date:** 2011-08-05 **Study First Submit QC Date:** 2011-08-05 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Società Italiana Radiologia Medica SIRM **Class:** UNKNOWN **Name:** Treviso cà Foncello Hospital **Class:** OTHER **Name:** University of Trieste **Class:** OTHER **Name:** Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia **Class:** OTHER **Name:** Santa Maria delle Grazie Hospital **Class:** OTHER **Name:** Azienda Ospedaliera Niguarda Cà Granda **Class:** OTHER **Name:** University of Rome Tor Vergata #### Lead Sponsor **Class:** OTHER **Name:** Stefano Colagrande #### Responsible Party **Investigator Affiliation:** University of Florence **Investigator Full Name:** Stefano Colagrande **Investigator Title:** Associate Professor of Radiology **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** One of the most recent and interesting field of diagnostic imaging is diffusion-weighted MR imaging (DW-MRI). Various studies evaluated the application of DW-MRI to diffuse liver disease and focal liver lesions providing controversial results, probably due to the difficult reproducibility of the apparent diffusion coefficient (ADC) measurements. It is conceivable that a wide inter/intra-individual variability actually exists in the apparent diffusion coefficient (ADC)-values, and that each apparent diffusion coefficient (ADC)-value presents an higher reliability in measuring the temporal changes of water diffusion within the same individual (longitudinal-evaluation), than in characterizing tissues between different patients (transverse-evaluation). For these reasons, some previous studies assessed the application of DW-MRI in predicting the chemotherapy (CHT) outcome in liver metastases. The rationale of these studies was the overt biochemical changes shown by the neoplastic cells after CHT and the sensitivity of DW-MRI in the identification of such changes. The same authors noticed that the metastatic lesions with the lowest ADC-values present also the best outcome after CHT. Moreover, these studies suggest that it could be possible to assess if each single patient will respond (R) or not (NR) to the CHT through liver DW-MRI performed from 3 days to 3 weeks after the beginning of CHT. **Detailed Description:** In R patients an increase of the mean diameter of the neoplastic cells should be present from the first week of CHT with a consequent reduction of the ADC-value. Then, the ADC-value should increase after 2-3 weeks due to the reduction of the cellular volume and to the increase of the membrane permeability. In NR patients, these biochemical changes should not be present with a consequent constant ADC-value before/after CHT. Our multicentre study will allow the recruitment of a higher number of patients vs. previous studies. Moreover, presently the outcome of CHT in liver metastases is evaluated only after 2-3 cycles of CHT according to the RECIST (Response-Evaluation-Criteria-In-Solid-Tumors) and then merely on a dimensional basis. Anyway, frequently liver metastases in R patients, can not show any significant dimensional change, while they present several biochemical/metabolic changes, not included in the RECIST, but probably detectable by DW-MRI. The principal objective of the study is the early assessment of CHT outcome in liver metastases and advanced hepatocellular carcinoma (HCC). Patients with liver metastasis will be stratified as R and NR on the basis of the contrast-enhanced CT examination performed 20 days after the beginning of the second cycle of CHT; patients with HCC undergoing therapy with Sorafenib will be stratified as R and NR on the basis of the contrast-enhanced CT examination performed 90 days after the beginning of the therapy. The ADC-values obtained before and after the first CHT cycle will be compared between each patient category to assess the grade of agreement between the dimensional and functional parameters. Moreover, the investigators' aim is to assess whether those liver metastases or HCCs presenting a lower ADC-value before CHT are actually more responsive to CHT in comparison to liver metastases and HCCs presenting a higher ADC-value. Secondary objectives: to propose some additional functional criteria to the RECIST 1.1 and mRECIST (for HCC) criteria based on water diffusion and biochemical changes of the neoplastic cells. As a further objective it is possible to hypothesize a different response to CHT of the different tumor histotypes detectable from the different ADC changes induced by CHT. Patient population Inclusion criteria: * of age, compliant, patients enrolled for CHT, without major contraindications to the MR examination; * non-confluent liver metastases, from every primary carcinoma histotype biopsy/surgical-proven, without intralesional necrosis/calcification involving \>30% of their volume; * multiple confluent hepatocellular carcinomas, histotype biopsy/surgical-proven in prevision of treatment with Sorafenib; * at least one marker lesion allowing reproducible ADC measurements, i.e. placed at the level of the lower right liver segments; * detection/enrolment by contrast-enhanced CT before CHT that allow to define the lesion size or the gross parenchymal involvement (if HCC). Each patient will sign an informed consent, after the procedure will be completely explained. For the metastasis: three diameter of each marker lesion will be measured, and the mean/minimal/maximal ADC±standard deviation will be quantified by region-of-interests (ROIs) placed within the lesion avoiding lesion margins and the necrotic/intratumoral calcification areas. All measurements will be repeated for three times even at the level of the adjacent liver parenchyma (within 3 cm from the lesion margins, keeping a ROI diameter \>2 cm). Consequently, the absolute values (s/mm2) of ADC, and the ADC percentages vs. the adjacent liver parenchyma measured at the different times will be compared. For HCC: three diameter of gross parenchymal involvement will be measured, and the mean/minimal/maximal ADC±standard deviation will be quantified by large region-of-interests (ROIs) placed within the liver lobe containing the involvement. All measurements will be repeated for three times even at the level of the adjacent normal liver parenchyma (within 3 cm from the lesion margins, keeping a ROI diameter \>2 cm). Consequently, the absolute values (s/mm2) of ADC, and the ADC percentages vs. the adjacent liver parenchyma measured at the different times will be compared. Imaging For metastasis: patients will be scanned by DW-MRI and contrast-enhanced CT before the beginning of CHT (Time 0). The time between the initial MRI and contrast-enhanced CT should not be superior to one week. MRI examination will be repeated within one week (Time 1) and 20 days from the beginning of the first cycle of CHT (Time 2), and 20 days from the beginning of the second cycle of CHT (Time 3). For HCC: patients will be scanned by DW-MRI and contrast-enhanced CT before the beginning of CHT (Time 0). The time between the initial MRI and contrast-enhanced CT should not be superior to one week. MRI examination will be repeated after 30 days (Time 1), 60 days and 90 days (Time 3) from the beginning of the CHT. Contrast-enhanced CT will be performed contemporarily or within one week after the last MRI examination. Contrast-enhanced CT examination will be performed according to an established protocol by using a 16/64-row equipment according to the centre involved, contrast bolus-track technology, slice- thickness reconstruction of 3 mm, before/after ev. injection of iodinated contrast agent (3 mL/s), during arterial/portal phase. All MR examinations will be carried out using the following 1.5-T units: * Gyroscan ACS NT Intera Release 12 (Philips, Eindhoven, The Netherlands) (Trieste and Florence), gradient strength, 30 mT/m; slew rate, 120 T/m/s; six-channel phased array multicoil; * Magnetom Avanto (Siemens, Erlangen, Germany) (Treviso and Napoli), gradient strength, 45 mT/m; slew rate, 200 T/m/s; 2 phased-array coils with 18 elements. The different MR equipments employed by the different centers will be calibrated by a dedicated phantom. The phased array multicoil will be adequately positioned to cover the upper abdomen of the subject lying in a supine position, the arms extended over the head to avoid artifacts. Patients, fasting from 4 hours, will be instructed to maintain a constant respiration depth, even with the possibility to use exogenous oxygen delivery to avoid deep respiration. All acquisitions will be obtained by single-shot sequence to obtain immediately/automatically the ADC-values. The protocol included the following acquisitions: 1. T2-weighted half-Fourier single-shot turbo spin-echo (HASTE) free-breath sequence; transverse/coronal plane; TR/TE, 810/80 ms; echo-train length, 69; slice number, 40; slice thickness, 5 mm; intersection gap, 10%; field of view, 300-420 mm; effective matrix size, 256 x 165; number signal averages (NSA), 1; total acquisition time, 2-3 min; 2. T1-weighted 2D gradient echo in/out phase breath-hold sequence; transverse plane; TR/TE, 231-121/ 14.6-2.3 ms; slice thickness, 5 mm; slice number, 24; intersection gap,10%; flip angle, 80°; sense factor, 1.5; field of view, 300-420 mm; effective matrix size, 256 x 165; NSA, 1; total acquisition time, 18 s; 3. D-weighted echo-planar imaging (EPI) single-shot free-breath sequences will be acquired on transverse plane with variable EPI factor and the following parameters. Fat suppression will be obtained by spectral pre-saturation inversion recovery. Isotropic motion probing gradients will be applied for each DwI acquisition and for each b-value will be obtained images and corresponding ADC map. The investigators presently define as R those patients who show a reduction of the liver metastasis or HCC diameter ≥30% on contrast-enhanced CT at three weeks after the beginning of the second CHT cycle; if not, it was considered NR. Changes in tumor size after treatment were calculated by using the formula % Vend =(VB -Vend)/VBx100, where VB was lesion size before treatment (maximum transverse diameter) and Vend was lesion size 20 days after the second administration. On the basis of the dimensional reduction of liver metastases and parenchymal involvement (for HCC) on contrast-enhanced CT on Time 3 vs. Time 0 scan, each patient will be classified as R or NR according to the RECIST and mRECIST criteria. Afterwards, on the basis of the ADC-values measured during the different MR examinations, the inter/intra-individual ADC-values will be compared to the results of contrast-enhanced CT to assess the relation between reduction of the liver metastasis diameter and: * increase of the ADC-value on Time 3 (after the end of CHT); * reduction of the ADC-value on Time 1 (very early assessment); * increase of the ADC-value on Time 2 (early assessment); and to assess whether the lesions with the highest pre-treatment ADC-value present also the highest dimensional reduction and the highest ADC-value at the end of CHT; In each center each evaluation will be performed three times by two blinded observers (all trained how to place the ROI by an inter-centre conference) to assess the reproducibility of all measurements. The observers who will assess the MR images will be different from the observers assessing the CT images and will not be aware about the size changes after CHT. The investigators will perform data mathematical fitting on multi-b DW-MRI data sets to calculate the true diffusion and the perfusion fraction. Statistical analysis will employ linear regression analysis to assess the association between the ADC-value changes and the CHT outcome. The transferability of the results of the present study to the clinical practice will be possible after the achievement of the primary objective, corresponding to the possibility of stratifying patients as R and NR to CHT through DW-MRI just after one week of treatment and/or with the pre-treatment ADC assessment. Nowadays, it is necessary to wait 20-30 days after the end of the second or third CHT cycle to know the individual outcome of CHT. This determines 2-3 months of ineffective therapy with consequent avoidable pain for the patients related to drug administration, and unusable costs. The possibility to know the response of each patient to CHT well in advance will allow avoiding vain drug administration to patients who could attempt a different treatment or drug combinations reducing treatment costs. The clinical transferability of the present study will be performed after the achievement of one or both the secondary objectives, corresponding to the identification of functional criteria based on water diffusion and biochemical features of the neoplastic cells which can be proposed as additional or alternative criteria to the RECIST 1.1 and mRECIST, and to the identification of a different response to CHT of different tumor histotypes. If only one of these objectives will be reached this study will achieve an important result, allowing a more correct assessment of individual response to CHT. ### Conditions Module **Conditions:** - Liver Metastases - Hepatocarcinoma **Keywords:** - liver - metastases - hepatocarcinoma - MR - DWI - chemotherapy ### Design Module #### Design Info **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 57 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The patients responding to the chemotherapy, i.e. who show at least a non progressive disease **Label:** Clinical Benefit #### Arm Group 2 **Description:** The patients non responding to the chemotherapy, i.e. who show a progressive disease **Label:** Non responder ### Outcomes Module #### Primary Outcomes **Description:** Linear regression analysis to assess the association between the ADC-value changes and the CHT outcome. **Measure:** Apparent Diffusion Coefficient (ADC) value changes of the lesion during chemotherapy. **Time Frame:** For metastasis: 2-4-8 weeks after CHT; for HCC: 30-60-90 days after CHT. ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * of age, compliant, patients enrolled for CHT, without major contraindications to the MR examination; * non-confluent liver metastases, from every primary carcinoma histotype biopsy/surgical-proven, without intralesional necrosis/calcification involving \>30% of their volume; * at least one marker lesion allowing reproducible ADC measurements, i.e. placed at the level of the lower right liver segments; * multiple confluent hepatocellular carcinomas, histotype biopsy/surgical-proven in prevision of treatment with Sorafenib; * detection/enrolment by contrast-enhanced CT before CHT that allow to define the lesion size or the gross parenchymal involvement (if HCC) Each patient will sign an informed consent, after the procedure will be completely explained. For the metastasis: Three diameter of each marker lesion will be measured, and the mean/minimal/maximal ADC±standard deviation will be quantified by region-of-interests (ROIs) placed within the lesion avoiding lesion margins and the necrotic/intratumoral calcification areas. For the hepatocarcinoma: Three diameter of gross parenchymal involvement will be measured, and the mean/minimal/maximal ADC±standard deviation will be quantified by large region-of-interests (ROIs) placed within the the lobe containing the involvement. All measurements will be repeated for three times even at the level of the adjacent liver parenchyma (within 3 cm from the lesion margins, keeping a ROI diameter \>2 cm). Consequently, the absolute values (s/mm2) of ADC, and the ADC percentages vs. the adjacent liver parenchyma measured at the different times will be compared. **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with liver metastases in chemotherapy and with hepatocarcinoma in therapy with Sorafenib ### Contacts Locations Module #### Locations **Location 1:** **City:** Florence **Country:** Italy **Facility:** Stefano Colagrande **Zip:** 50134 #### Overall Officials **Official 1:** **Affiliation:** University of Florence **Name:** Stefano Colagrande, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009385 - Term: Neoplastic Processes - ID: D000009369 - Term: Neoplasms - ID: D000010335 - Term: Pathologic Processes - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000004066 - Term: Digestive System Diseases - ID: D000008107 - Term: Liver Diseases - ID: D000000230 - Term: Adenocarcinoma - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M9613 - Name: Carcinoma, Hepatocellular - Relevance: HIGH - As Found: Hepatocarcinoma - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Metastases - ID: M11113 - Name: Liver Neoplasms - Relevance: HIGH - As Found: Liver Metastases - ID: M12330 - Name: Neoplastic Processes - 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: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - 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 ### Condition Browse Module - Meshes - ID: D000009362 - Term: Neoplasm Metastasis - ID: D000008113 - Term: Liver Neoplasms - ID: D000006528 - Term: Carcinoma, Hepatocellular ### 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 ### Misc Info Module - Version Holder: 2024-05-24