Colchicine in HFpEF (COLpEF)

April 24, 2023 updated by: Montreal Heart Institute

A Biomarker Study Assessing the Effects of Colchicine on Inflammation and Extra-Cellular Matrix Turnover in Patients With Heart Failure and Preserved Ejection Fraction.

Heart failure is a growing epidemic that affects up to 500,000 individuals in Canada, with 50,000 new cases being diagnosed each year. Half of these will have HF with preserved ejection fraction (HFpEF).

HFpEF has been associated with high rates of morbidity, mortality, and health care expenditures. Its pathophysiology remains poorly understood, and positive medication trial results to date have been rare.

Inflammation is strongly associated with a profibrotic activation in HFpEF, which is in turn associated with the severity and prognosis of the disease.

Colchicine is a potent anti-inflammatory drug which properties relate to the suppression of tubulin polymerization and inflammasome inhibition, thus reducing the production of IL-1β and IL-18.

The investigators thus propose a pilot study of 6 months follow-up duration that will test the efficacy and safety of 2 dosing regimens of colchicine (vs. placebo) in patients with HFpEF.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montréal, Quebec, Canada, H1T 1C8
        • Montreal Heart Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients ≥ 40 years of age;
  • Chronic symptomatic HFpEF defined as follows: left ventricular ejection fraction (LVEF) > or = 45% within 6 months prior to screening visit (regardless of the imaging modality);
  • No recent change in RAAS inhibitors regimen for at least 1 month before enrolment (excluding changes in oral diuretics);
  • NYHA functional class II to IV;
  • Evidence of structural heart disease defined by at least 1 of the following echocardiography findings: LV hypertrophy (i.e. septal or posterior wall thickness ≥1.1 cm) or left atrial enlargement (i.e., width ≥3.8 cm, length ≥5.0 cm, area ≥20 cm2, volume ≥55 ml, or volume index ≥29 ml/m2);
  • Patients with a diagnosis of acute heart failure (treated with intravenous diuretics) within 12 months before screening; or an NT-proBNP of ≥300 pg/ml if in sinus rhythm, and ≥900 pg/ml if in atrial fibrillation within 30 days before screening (if multiple measurements, consider the highest);

  • At least one of the following criteria defining chronic enhanced inflammatory milieu:

    1. Obesity, defined as body mass index (BMI) > 30kg/m2,
    2. Type 2 diabetes according to Diabetes Canada definition (http://guidelines.diabetes.ca/cpg/chapter3), and regardless of therapy,
    3. Evidence of pathological systemic inflammation including: high hs-CRP levels (hs-CRP>2mg/L), or the combination of high neutrophil count and low lymphocyte count (Neutrophil to Lymphocyte Ratio >3) within 30 days before screening (if multiple measurements, consider the higher),
  • Subjects with the capacity to provide informed consent.

Exclusion Criteria:

  • Any prior measurement of LVEF <40%;
  • Patients with a diagnosis of hypertrophic or infiltrative cardiomyopathy;
  • Presence of hemodynamically significant valvular heart disease in the opinion of the investigator;
  • Presence of active infection within the 3 months prior to visit 1 needing antibiotics (excluding COVID-19);
  • Acute decompensated HF, acute coronary syndrome (including myocardial infarction), cardiac surgery, other major cardiovascular surgery, or urgent percutaneous coronary intervention (PCI) within the 3 months prior to visit 1;
  • Elective PCI within 30 days prior to visit 1;
  • Known or clinically judged significant (i.e., angina with CCS class >2/4) epicardial coronary artery disease (CAD) that has not been revascularized (revascularized CAD is defined by a history of myocardial infraction, percutaneous intervention, or coronary artery bypass grafting);
  • Changes renin-angiotensin-aldosterone system (RAAS) inhibitors regimen within 30 days prior to screening visit;
  • History of hypersensitivity to colchicine;
  • Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or atrial flutter with a resting ventricular rate >120 beats per minute;
  • Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or is likely to prevent the patient from complying with the requirements of the study or completing the study;
  • Evidence of hepatic disease as determined by any 1 of the following: serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) values exceeding 3× the upper limit of normal, bilirubin>1.5 mg/dL (>25.65 μmol/L) at baseline visit; or patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease;
  • Patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at baseline visit;
  • History or presence of any other disease with a life expectancy of <1 year;
  • Patient with inflammatory bowel disease (Crohn's disease or ulcerative colitis) or patient with chronic diarrhea;
  • Patient with pre-existent progressive neuromuscular disease;
  • Patient currently taking colchicine for other indications (mainly chronic indications represented by Familial Mediterranean Fever or gout). There is no wash-out period required for patients who have been treated with colchicine and stopped treatment prior to enrolment;
  • Patients currently under long-term steroid medication for a chronic condition, or steroid medication within 30 days before screening;
  • Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
  • Positive pregnancy test result at the screening visit, and females of childbearing potential who do not agree to use adequate method of contraception for the duration of the study; acceptable means of birth control include: implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, male or female condoms with spermicide, abstinence, or a sterile sexual partner.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Patients meeting all inclusion criteria and no exclusion criteria will be randomly assigned to receive either colchicine (0.5mg once daily), colchicine (0.5mg twice daily) or matched placebo (1:1:1 allocation ratio), in addition to standard of care.
Active Comparator: Colchicine 0.5 mg die
Drug: Colchicine
Patients meeting all inclusion criteria and no exclusion criteria will be randomly assigned to receive either colchicine (0.5mg once daily), colchicine (0.5mg twice daily) or matched placebo (1:1:1 allocation ratio), in addition to standard of care.
Active Comparator: Colchicine 0.5 mg bid
Drug: Colchicine
Patients meeting all inclusion criteria and no exclusion criteria will be randomly assigned to receive either colchicine (0.5mg once daily), colchicine (0.5mg twice daily) or matched placebo (1:1:1 allocation ratio), in addition to standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in hs-CRP (C reactive protein)
Time Frame: Change from baseline to 6 months in hs-CRP
The primary endpoint will be the change from baseline to 6 months in hs-CRP (mg/L), a circulating biomarker of inflammation.
Change from baseline to 6 months in hs-CRP

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in circulating biomarkers of hemodynamic stress
Time Frame: Change from baseline to 6 months in other biomarkers
Change in circulating biomarkers of hemodynamic stress (N-terminal pro-brain natriuretic peptide (NT-proBNP, in pg/mL))
Change from baseline to 6 months in other biomarkers
Change in circulating biomarkers of myocardial injury
Time Frame: Change from baseline to 6 months in other biomarkers
Change in circulating biomarkers of myocardial injury (hs-TnT, Troponin, in ng/L)
Change from baseline to 6 months in other biomarkers
Change in left ventricular (LV) diastolic function
Time Frame: Change from baseline to 6 months in LV diastolic function
Change in a combination of echocardiography-based measures assessing left ventricular (LV) diastolic function
Change from baseline to 6 months in LV diastolic function
Change in functional status and symptoms
Time Frame: Change from baseline to 6 months in functional status and symptoms
Change in functional status and New York Heart Association (NYHA) class
Change from baseline to 6 months in functional status and symptoms

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety endpoints
Time Frame: Monitoring of adverse events will throughout the study, from baseline to 6 months in exploratory endpoints
Monitoring of adverse events will include gastrointestinal manifestations, hepatotoxicity, myelotoxicity, myotoxicity, and risk of infections.
Monitoring of adverse events will throughout the study, from baseline to 6 months in exploratory endpoints

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montreal Heart Institute

Investigators

  • Principal Investigator: Nadia Bouabdallaoui, MD, Montreal Heart Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 17, 2022

Primary Completion (Actual)

March 7, 2023

Study Completion (Actual)

March 7, 2023

Study Registration Dates

First Submitted

March 29, 2021

First Submitted That Met QC Criteria

April 20, 2021

First Posted (Actual)

April 23, 2021

Study Record Updates

Last Update Posted (Actual)

April 26, 2023

Last Update Submitted That Met QC Criteria

April 24, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MP-33-2021-2929

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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