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COLchicine and Thiamine in Heart Failure Due to Ischemic Heart Disease (COLT-HF)

Primary Purpose

Heart Failure

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Colchicine 0.5 MG
Colchicine placebo
Thiamine Mononitrate 300 mg
Sponsored by
Hamilton Health Sciences Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age >/= 45 years Documented ischemic HF as the etiology of HF, which includes: a prior history of CAD (defined as a history of myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or non-invasive or invasive cardiac testing consistent with a diagnosis of CAD), and determination of CAD to be the cause primary cause of HF based on local investigator assessment New York Heart Association (NYHA) class II-IV symptoms Documented LVEF </= 45% within 1 year prior to enrollment Optimization of HF treatment based on local practice. Ambulatory HF patients or stable hospitalized patients with HF will both be eligible for enrollment in the trial. For hospitalized patients, enrollment will require i) evidence of clinical stability from HF defined as no use of an inotropic agent or intravenous diuretic agent in the prior 24, and ii) expected discharge from hospital in the next 72 hours. Exclusion Criteria: Female who is pregnant, breast-feeding, or of childbearing potential and not using an effective form of birth control* Regular or required use colchicine or thiamine for other clinical indications.** History of allergic reaction to colchicine or to thiamine; or current or planned use of cyclosporine, verapamil, diltiazem, azole antifungal, macrolide antibiotic (except azithromycin), or HIV protease inhibitor Use of a ventricular assist device or prior heart transplant Coronary revascularization (coronary artery bypass graft surgery or percutaneous coronary intervention) within the 4 weeks prior to enrollment, or planned within the next 4 weeks. Severe valvular disease Chronic and severe renal dysfunction defined as eGFR < 15 mL/min/1.73m2 based on local laboratory measurement done within 6 months prior to run-in*** History of liver cirrhosis Active malignancy (excluding basal cell or treated squamous cell carcinoma of the skin) requiring treatment and with a life-expectancy of < 2 years. Concurrent use of other experimental pharmacologic agents -

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Experimental

    Arm Label

    Colchicine versus placebo

    Thiamine versus no thiamine

    Arm Description

    Randomization to colchicine or placebo

    Randomization to thiamine or to no thiamine in a PROBE design

    Outcomes

    Primary Outcome Measures

    Colchicine arm: Time to first occurrence of a CV death, a HF event, MI, stroke, or arterial revascularization
    Thiamine arm: Time to first occurrence of a CV death, or a HF event

    Secondary Outcome Measures

    Time to death
    Time to first hospitalization

    Full Information

    First Posted
    May 15, 2023
    Last Updated
    September 25, 2023
    Sponsor
    Hamilton Health Sciences Corporation
    Collaborators
    Population Health Research Institute, Canadian Institutes of Health Research (CIHR)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05873881
    Brief Title
    COLchicine and Thiamine in Heart Failure Due to Ischemic Heart Disease
    Acronym
    COLT-HF
    Official Title
    COLchicine and Thiamine in Heart Failure Due to Ischemic Heart Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 2023 (Anticipated)
    Primary Completion Date
    June 2027 (Anticipated)
    Study Completion Date
    June 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Hamilton Health Sciences Corporation
    Collaborators
    Population Health Research Institute, Canadian Institutes of Health Research (CIHR)

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The goal of this 2x2 factorial clinical trial is to test the efficacy of i) colchicine, and ii) thiamine in heart failure (HF) secondary to ischemic heart disease. The main questions it aims to answer are: Does colchicine reduce the risk of cardiovascular (CV) death, a HF event, or an ischemic CV event Does thiamine reduce the risk of cardiovascular (CV) death, or a HF event Participants will undergo the following procedures: Run-in: All participants will receive colchicine 0.5 mg daily to assess drug tolerance over a 3-4 week period. Randomization: If colchicine is tolerated during run-in, eligible participants will be randomized in a 2x2 factorial design to receive i) colchicine 0.5mg daily or placebo, and ii) thiamine 300mg daily or no thiamine. Follow-up: Clinical outcomes, side effects, adverse events, and drug adherence will be captured during follow-up

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Heart Failure

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Factorial Assignment
    Model Description
    Factorial 1: Colchicine 0.5 mg daily or placebo Factorial 2: Thiamine 300mg daily or no thiamine
    Masking
    ParticipantOutcomes Assessor
    Masking Description
    Factorial 1: Placebo controlled. Factorial 2: Prospective Randomized Open Blinded End-point (PROBE) design
    Allocation
    Randomized
    Enrollment
    2500 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Colchicine versus placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Randomization to colchicine or placebo
    Arm Title
    Thiamine versus no thiamine
    Arm Type
    Experimental
    Arm Description
    Randomization to thiamine or to no thiamine in a PROBE design
    Intervention Type
    Drug
    Intervention Name(s)
    Colchicine 0.5 MG
    Intervention Description
    Oral colchicine 0.5 mg daily
    Intervention Type
    Drug
    Intervention Name(s)
    Colchicine placebo
    Intervention Description
    Placebo colchicine daily
    Intervention Type
    Drug
    Intervention Name(s)
    Thiamine Mononitrate 300 mg
    Intervention Description
    Thiamine Mononitrate 300 mg daily
    Primary Outcome Measure Information:
    Title
    Colchicine arm: Time to first occurrence of a CV death, a HF event, MI, stroke, or arterial revascularization
    Time Frame
    3.5 years
    Title
    Thiamine arm: Time to first occurrence of a CV death, or a HF event
    Time Frame
    3.5 years
    Secondary Outcome Measure Information:
    Title
    Time to death
    Time Frame
    3.5 years
    Title
    Time to first hospitalization
    Time Frame
    3.5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    45 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age >/= 45 years Documented ischemic HF as the etiology of HF, which includes: a prior history of CAD (defined as a history of myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or non-invasive or invasive cardiac testing consistent with a diagnosis of CAD), and determination of CAD to be the cause primary cause of HF based on local investigator assessment New York Heart Association (NYHA) class II-IV symptoms Documented LVEF </= 45% within 1 year prior to enrollment Optimization of HF treatment based on local practice. Ambulatory HF patients or stable hospitalized patients with HF will both be eligible for enrollment in the trial. For hospitalized patients, enrollment will require i) evidence of clinical stability from HF defined as no use of an inotropic agent or intravenous diuretic agent in the prior 24, and ii) expected discharge from hospital in the next 72 hours. Exclusion Criteria: Female who is pregnant, breast-feeding, or of childbearing potential and not using an effective form of birth control* Regular or required use colchicine or thiamine for other clinical indications.** History of allergic reaction to colchicine or to thiamine; or current or planned use of cyclosporine, verapamil, diltiazem, azole antifungal, macrolide antibiotic (except azithromycin), or HIV protease inhibitor Use of a ventricular assist device or prior heart transplant Coronary revascularization (coronary artery bypass graft surgery or percutaneous coronary intervention) within the 4 weeks prior to enrollment, or planned within the next 4 weeks. Severe valvular disease Chronic and severe renal dysfunction defined as eGFR < 15 mL/min/1.73m2 based on local laboratory measurement done within 6 months prior to run-in*** History of liver cirrhosis Active malignancy (excluding basal cell or treated squamous cell carcinoma of the skin) requiring treatment and with a life-expectancy of < 2 years. Concurrent use of other experimental pharmacologic agents -
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Philip G Joseph, M.D.
    Phone
    19055212100
    Ext
    40743
    Email
    philip.joseph@phri.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Philip G Joseph, M.D.
    Organizational Affiliation
    Population Health Research Institute
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    COLchicine and Thiamine in Heart Failure Due to Ischemic Heart Disease

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