Colchicine in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

I.M. Sechenov First Moscow State Medical University

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Colchicine

HFpEF - Heart Failure With Preserved Ejection Fraction

Treatments

Drug: Colchicine

Study type

Interventional

Funder types

Other

Identifiers

NCT05637398

03-22

Details and patient eligibility

About

Heart failure with preserved left ventricular ejection fraction (HFpEF) is a syndrome associated with high morbidity and mortality rates. Systemic low-grade inflammation is acknowledged to be a fundamental pathophysiological mechanism of HFpEF. Interventions targeting inflammatory pathway is understudied in HFpEF. Colchicine is a safe and well tolerated anti-inflammatory drug, which interferes with several steps in the inflammatory process. The drug has been extensively studied in different cardiovascular pathologies except HFpEF. We assume that colchicine decreases inflammation and reduces sST2 levels in HFpEF.

Full description

HFpEF is a syndrome associated with high morbidity and mortality rates. The underlying mechanisms of the syndrome are not fully understood. Systemic low-grade inflammation is acknowledged to be a fundamental pathophysiological mechanism of HFpEF, which facilitates cardiomyocyte stiffness and myocardial fibrosis development. However, anti-inflammatory treatment approaches are largely under studied. Colchicine is a safe and well tolerated anti-inflammatory drug, which interferes with several steps in the inflammatory process, resulting in suppression of a number of pro-inflammatory pathways and cytokines release, including IL-1, hsCRP. The drug has been extensively studied in patients with coronary artery disease (COLCOT, LoDoCo2) and showed significant reduction in risk of cardio-vascular events, as well as inflammation. Post-hoc analysis of in the CANTOS study investigated the effect of monoclonal antibody targeting interleukin-1β in patients with prior myocardial infarction, showed a reduction in heart failure (HF) hospitalization of patients with elevations in high-sensitivity C-reactive protein (hsCRP). There is no data available regarding the effect of Colchicine on HFpEF patients. Soluble suppression of tumourigenicity 2 (sST2), a member of the interleukin (IL)-1 receptor family, which is not restricted to inflammation, but is also expressed in cardiomyocytes, fibroblast and endothelial cells of cardiac microvessels in response to myocardial stress antagonizing cardioprotective effects of IL-33/ST2 system. In HFpEF, sST2 associated with worse clinical signs and symptoms, co-morbidities, biomarkers of fibrosis and neurohormonal activation. Elevated levels of sST2 are acknowledged as a predictor of worse prognosis in both HF with reduced ejection fraction (HFrEF) and HFpEF. We assume that colchicine decreases inflammation and reduces sST2 levels in HFpEF.

Enrollment

40 estimated patients

Sex

All

Ages

40 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

40 years of age, male and female
Left ventricular ejection fraction (LVEF) ≥ 50%
Symptoms and signs of heart failure
N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml at baseline (patients in atrial fibrillation at baseline NT-proBNP ≥ 600 pg/ml), left atrial volume index (LAVI) >34 mL/m2 or a left ventricular mass index (LVMI) =115 g/m2 for males and =95 g/m2 for females
body mass index (BMI) > 30kg/m2 or diabetes mellitus

Exclusion criteria

Hypertrophic cardiomyopathy, constrictive pericarditis, or cardiac amyloidosis
Acute decompensation of HF in the last 1 month
Valvular heart disease
Prior history of LVEF below 50%
Acute myocardial infarction in the last 3 months, cardiac surgery or cerebrovascular accident within the recent 6 months
Any active or chronic inflammatory diseases or infections
Patients with indication for colchicine therapy or history of colchicine intolerance
Severe hepatic (alanine aminotransferase N3 upper limit of normal or renal dysfunction (estimated glomerular filtration rate <45 mL/min per 1.73m2)
Severe nervous system diseases
History of any malignancy or suffering from cancer
Lack of informed consent