Reversing Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction

Heart Failure With Preserved Ejection Fraction Clinical Trial

— COL-Micro-HF  

Official title:

Reversing Microvascular Dysfunction in Heart Failure With Ejection Fraction > 40% Using Colchicine (The COL-Micro-HF Study)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06217120
• Other study ID #: ICM 2024-3370
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: March 1, 2024
• Est. completion date: March 1, 2026

Study information

• Verified date: January 2024
• Source: Montreal Heart Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

This will be a pilot mechanistic study. Patients will be randomly assigned in a 1:1 ratio to receive colchicine 0.5 milligram (mg) daily or a matched placebo. Follow-up will occur six months after randomization. The study aims to test the impact of reducing inflammation using a pharmacological strategy to reverse CMD in patients with HF and EF above 40%. The investigators will test the effect of colchicine on the change in coronary flow reserve (CFR), a marker for CMD, compared to placebo. The investigators will assess CMD using adenosine-based positron emission tomography (PET). The primary objective will be to compare changes in CFR between six months and baseline according to therapy. The primary Endpoint will be the change from baseline to 6 months in CFR, a marker of CMD.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: March 1, 2026
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Subjects = 40 years of age,

2. 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:

1. HF requiring hospitalization and IV diuretics within 12 months of study entry, or

2. NTproBNP > or = 150pg/ml in sinus rhythm or NTproBNP > or = 450pg/ml in chronic atrial fibrillation,

3. New York Heart Association Class, NYHA functional class II to (ambulatory) IV,

4. Evidence of pathological systemic inflammation: high C-reactive protein, hs-CRP levels (hs-CRP > or = 5mg/L),

5. Subjects with the capacity to provide informed consent.

Exclusion Criteria:

1. Patients with a diagnosis of infiltrative cardiomyopathy,

2. Presence of severe valvular heart disease,

3. Presence of active infection within the 3 months prior to enrollment needing antibiotics (excluding COVID (Coronavirus disease)-19),

4. 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,

5. 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),

6. History of hypersensitivity to colchicine,

7. 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,

8. 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,

9. Subject with inflammatory bowel disease (Crohn's disease or ulcerative colitis) or patient with chronic diarrhea,

10. Patient with pre-existent progressive neuromuscular disease,

11. 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,

12. Patients under long-term steroid medication for a chronic condition,

13. Contraindication to dipyridamole-containing medication, acute myocardial infarction or unstable angina in the past 48h,

14. 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,

15. History or presence of any other disease with a life expectancy of <1 year,

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Microvascular Coronary Artery Disease
• Myocardial Ischemia

Intervention

Drug:
• Colchicine
Colchicine 0.5 mg daily
• Placebo
Placebo once daily

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Montreal Heart Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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