Colchicine in patients with heart failure and preserved left ventricular ejection fraction: rationale and design of a prospective, randomised, open-label, crossover clinical trial

Abstract

IntroductionSystemic low-grade inflammation is a fundamental pathophysiological mechanism of heart failure with preserved left ventricular ejection fraction (HFpEF). The efficacy of anti-inflammatory therapy in HFpEF is largely understudied. The aim of the study is to assess the anti-inflammatory effect of colchicine in HFpEF by looking at inflammatory biomarkers: high-sensitivity C reactive protein (hsCRP) and soluble suppression of tumorigenicity 2 (sST2).Methods and analysisThis is a single-centre, prospective, randomised controlled, open-label, blinded-endpoint crossover clinical trial of stable but symptomatic patients with HFpEF. Patients will be randomised to either colchicine treatment 0.5 mg two times per day or usual care for 12 weeks followed by a 2-week washout period and crossover to 12 weeks of treatment with the alternate therapy. The primary objective is to investigate if administration of colchicine compared with usual care reduces inflammation in patients with HFpEF measured by primary endpoint sST2 and co-primary endpoint hsCRP at baseline and 12-week follow-up. Secondary objective is to determine if treatment with colchicine influences N-terminal pro-B-type natriuretic peptide levels, left ventricular diastolic function and remodelling, right ventricular systolic function and left atrial volumetric characteristics. We are aiming to enrol a total of 40 participants. This trial will answer the question if colchicine treatment reduces systemic low-grade inflammation and influences left ventricular diastolic function and remodelling with patients with HFpEF.Ethics and disseminationEthical approval was obtained from the Ethics Committee of Sechenov University (reference: 03-22).Trial registration numberNCT05637398.