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COLpEF: Colchicine in HFpEF

Sponsor
Montreal Heart Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT04857931
Collaborator
(none)
426
Enrollment
1
Location
3
Arms
27.5
Anticipated Duration (Months)
15.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
426 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Biomarker Study Assessing the Effects of Colchicine on Inflammation and Extra-Cellular Matrix Turnover in Patients With Heart Failure and Preserved Ejection Fraction.
Actual Study Start Date :
Jun 17, 2022
Anticipated Primary Completion Date :
May 1, 2024
Anticipated Study Completion Date :
Oct 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Colchicine 0.5 mg die

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

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.
Placebo Comparator: Placebo

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.

Outcome Measures

Primary Outcome Measures

  1. Change in hs-CRP (C reactive protein) [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.

Secondary Outcome Measures

  1. Change in circulating biomarkers of hemodynamic stress [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))

  2. Change in circulating biomarkers of myocardial injury [Change from baseline to 6 months in other biomarkers]

    Change in circulating biomarkers of myocardial injury (hs-TnT, Troponin, in ng/L)

  3. Change in left ventricular (LV) diastolic function [Change from baseline to 6 months in LV diastolic function]

    Change in a combination of echocardiography-based measures assessing left ventricular (LV) diastolic function

  4. Change in functional status and symptoms [Change from baseline to 6 months in functional status and symptoms]

    Change in functional status and New York Heart Association (NYHA) class

Other Outcome Measures

  1. Safety endpoints [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
40 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Patients ≥ 40 and < 80 years of age;

  • Chronic symptomatic HFpEF defined as follows: left ventricular ejection fraction (LVEF) > or = 45% by echocardiography within 6 months prior to screening visit;

  • Stable clinically and therapeutically for at least 1 month before enrolment; *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);

  • an NT-proBNP of ≥600 pg/ml if in sinus rhythm, and ≥1800 pg/ml if in atrial fibrillation;

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

  1. Obesity, defined as body mass index (BMI) > 30kg/m2,

  2. Diabetes mellitus,

  3. Evidence of pathological systemic inflammation including: high hs-CRP levels (hs-CRP>5mg/L), or the combination of high neutrophil count and low lymphocyte count (Neutrophil to Lymphocyte Ratio >3).

Exclusion Criteria:

  • Patients > 80 years of age;

  • Any prior echocardiographic measurement of LVEF <45%;

  • Presence of clinical, biological or echocardiography signs of cardiac amyloidosis;

  • Presence of hemodynamically significant valvular heart disease in the opinion of the investigator;

  • Presence of active infection within the 3 months prior to enrolment;

  • 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 baseline visit or an elective PCI within 30 days prior to baseline visit;

  • Current acute decompensated HF requiring augmented therapy with diuretic agents, vasodilator agents, and/or inotropic drugs;

  • Changes in diuretics and / or renin-angiotensin-aldosterone system (RAAS) inhibitors regimen within 30 days prior to 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;

  • Women of child-bearing potential;

  • 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);

  • Patients currently under long-term anti-inflammatory medication for a chronic condition (steroids, NSAIDS);

  • Patient considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Montreal Heart Institute Montréal Quebec Canada H1T 1C8

Sponsors and Collaborators

  • Montreal Heart Institute

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Montreal Heart Institute
ClinicalTrials.gov Identifier:
NCT04857931
Other Study ID Numbers:
  • MP-33-2021-2929
First Posted:
Apr 23, 2021
Last Update Posted:
Jul 7, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Heart Failure
Inflammation
Colchicine

Study Results

No Results Posted as of Jul 7, 2022