Reversing Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction

NCT06217120 | Not Yet Recruiting Phase 2

• 1 other identifier: ICM 2024-3370
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the impact of colchicine on the change in coronary flow reserve (CFR), a marker for coronary microvascular dysfunction (CMD), compared to placebo in patients with heart failure and ejection fraction above 40% (including patients with improved EF).

Conditions

Heart Failure With Preserved Ejection Fraction; Microvascular Coronary Artery Disease

Keywords

Heart Failure with Preserved Ejection Fraction; Microvascular Coronary Artery Disease; Inflammation; Colchicine

Outcome Measures

Primary Outcomes (1)

• Change in coronary flow reserve (CFR) between baseline and six months

  The primary endpoint will be the change from baseline to 6 months in CFR, a marker of coronary microvascular dysfunction (CMD), according to therapy (colchicine vs. placebo). Assessment of CFR will be based on 82-Rubidium Positron emission tomography (82Rb-PET)-myocardial perfusion imaging, performed at baseline and 6-month follow up.

  Baseline and 6 months

Study Arms (2)

COLCHICINE

ACTIVE COMPARATOR

Drug: Colchicine

PLACEBO

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Colchicine DRUG

Colchicine 0.5 mg daily

COLCHICINE

Placebo DRUG

Placebo once daily

PLACEBO

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects ≥ 40 years of age,
• Chronic symptomatic HF and left ventricular ejection fraction (LVEF) \> 40% within 12 months prior to the screening visit (regardless of the imaging modality) documented by one of the following:
• HF requiring hospitalization and IV diuretics within 12 months of study entry, or
• NTproBNP \> or = 150pg/ml in sinus rhythm or NTproBNP \> or = 450pg/ml in chronic atrial fibrillation,
• New York Heart Association Class, NYHA functional class II to (ambulatory) IV,
• Evidence of pathological systemic inflammation: high C-reactive protein, hs-CRP levels (hs-CRP \> or = 5mg/L),
• Subjects with the capacity to provide informed consent.

You may not qualify if:

• Patients with a diagnosis of infiltrative cardiomyopathy,
• Presence of severe valvular heart disease,
• Presence of active infection within the 3 months prior to enrollment needing antibiotics (excluding COVID (Coronavirus disease)-19),
• Acute decompensated HF, acute coronary syndrome (including MI), cardiac surgery, other major cardiovascular surgery, or urgent percutaneous coronary intervention (PCI) within the 3 months prior to enrollment,
• Known or clinically judged significant (i.e., angina with CCS (Canadian Cardiovascular Society) class \> 2/4) epicardial coronary artery disease (CAD) that has not been revascularized (revascularized CAD is defined by a history of myocardial infarction, percutaneous intervention, or coronary artery bypass grafting),
• History of hypersensitivity to colchicine,
• Evidence of hepatic disease as determined by any 1 of the following: AST or ALT values exceeding 3× the upper limit of normal at enrollment; 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 enrollment,
• Subject 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 under long-term steroid medication for a chronic condition,
• Contraindication to dipyridamole-containing medication, acute myocardial infarction or unstable angina in the past 48h,
• Positive pregnancy test results at the screening visit, and females of childbearing potential who do not agree to use adequate methods 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,
• History or presence of any other disease with a life expectancy of \<1 year,

Sponsors & Collaborators

• Montreal Heart Institute: lead

Study Sites (1)

Montreal Heart Institute

Montreal, Quebec, H1T1C8, Canada

Location

MeSH Terms

Conditions

Inflammation

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a pilot mechanistic study. Patients will be randomly assigned in a 1:1 ratio to receive colchicine 0.5 mg daily or a matched placebo. Follow-up will occur at 6 months after randomization.

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: January 22, 2024
• Study Start: March 1, 2024
• Primary Completion: October 1, 2025
• Study Completion: March 1, 2026
• Last Updated: January 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CA (1)