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

Sponsor

Hamilton Health Sciences Corporation (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05873881

Collaborator

Population Health Research Institute (Other), Canadian Institutes of Health Research (CIHR) (Other)

2,500

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The goal of this 2x2 factorial clinical trial is to test the efficacy of i) colchicine, and

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

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: Colchicine 0.5 MG Drug: Colchicine placebo Drug: Thiamine Mononitrate 300 mg	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2500 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

Factorial 1: Colchicine 0.5 mg daily or placebo Factorial 2: Thiamine 300mg daily or no thiamineFactorial 1: Colchicine 0.5 mg daily or placebo Factorial 2: Thiamine 300mg daily or no thiamine

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Factorial 1: Placebo controlled. Factorial 2: Prospective Randomized Open Blinded End-point (PROBE) design

Primary Purpose:

Treatment

Official Title:

COLchicine and Thiamine in Heart Failure Due to Ischemic Heart Disease

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2027

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Colchicine versus placebo Randomization to colchicine or placebo	Drug: Colchicine 0.5 MG Oral colchicine 0.5 mg daily Drug: Colchicine placebo Placebo colchicine daily
Experimental: Thiamine versus no thiamine Randomization to thiamine or to no thiamine in a PROBE design	Drug: Thiamine Mononitrate 300 mg Thiamine Mononitrate 300 mg daily

Arm

Intervention/Treatment

Placebo Comparator: Colchicine versus placebo

Randomization to colchicine or placebo

Drug: Colchicine 0.5 MG

Oral colchicine 0.5 mg daily

Drug: Colchicine placebo

Placebo colchicine daily

Experimental: Thiamine versus no thiamine

Randomization to thiamine or to no thiamine in a PROBE design

Drug: Thiamine Mononitrate 300 mg

Thiamine Mononitrate 300 mg daily

Outcome Measures

Primary Outcome Measures

Colchicine arm: Time to first occurrence of a CV death, a HF event, MI, stroke, or arterial revascularization [3.5 years]
Thiamine arm: Time to first occurrence of a CV death, or a HF event [3.5 years]

Secondary Outcome Measures

Time to death [3.5 years]
Time to first hospitalization [3.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

All

Accepts 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 -