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

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

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Colchicine 0.5 MG; Drug: Colchicine placebo; Drug: Thiamine Mononitrate 300 mg

• Study Type: Interventional
• Enrollment (Estimated): 2500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Philip G Joseph, M.D.; Phone Number: 40743 905-521-2100; Email: philip.joseph@phri.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton Health Sciences Corporation
      • Contact: Katie Porter; Phone Number: 74559 905-521-2100; Email: porterk@hhsc.ca
      • Principal Investigator: Phil G. Joseph, MD
      • Sub-Investigator: Eva Lonn, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >/= 45 years

2. Documented ischemic HF as the etiology of HF, which includes:

   1. 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
   2. determination of CAD to be the cause primary cause of HF based on local investigator assessment
3. New York Heart Association (NYHA) class II-IV symptoms
4. Documented LVEF </= 45% within 1 year prior to enrollment
5. Optimization of HF treatment based on local practice.
6. 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:

1. Female who is pregnant, breast-feeding, or of childbearing potential and not using an effective form of birth control*
2. Regular or required use colchicine or thiamine for other clinical indications.**
3. 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
4. Use of a ventricular assist device or prior heart transplant
5. 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.
6. Severe valvular disease
7. 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***
8. History of liver cirrhosis
9. Active malignancy (excluding basal cell or treated squamous cell carcinoma of the skin) requiring treatment and with a life-expectancy of < 2 years.
10. Concurrent use of other experimental pharmacologic agents -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Time to death	3.5 years
Time to first hospitalization	3.5 years

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Canadian Institutes of Health Research (CIHR); Population Health Research Institute
• Investigators: Principal Investigator: Philip G Joseph, M.D., Population Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 15, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Failure; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Micronutrients; Vitamins; Vitamin B Complex; Gout Suppressants; Colchicine; Thiamine
• Other Study ID Numbers: PHRI.COLT-HF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No