The effects of low-dose colchicine on the progression of aortic valve stenosis: Rationale, design, and baseline characteristics of the Colchicine and Inflammation in Aortic Stenosis (CHIANTI) trial

BACKGROUND: Aortic valve stenosis (AS) is one of the most common valvular heart diseases worldwide. Its prevalence increases with age and is expected to rise further as the population ages. Untreated severe AS carries a 2-year mortality rate exceeding 50%. Furthermore, surveillance and management of AS impose a significant burden on healthcare systems. Therefore, effective pharmacological strategies are urgently needed to slow or halt the progression of AS. RATIONALE AND DESIGN: Inflammation plays a central role in the pathogenesis of both atherosclerosis and AS. Anti-inflammatory therapy with low-dose colchicine reduces cardiovascular events in patients with coronary artery disease, but its efficacy has not been tested in AS. Colchicine and Inflammation in Aortic Stenosis (CHIANTI) is an investigator-initiated, placebo-controlled, double-blind, multicenter, randomized trial involving 150 patients with moderate AS. After confirming tolerance during a two-week run-in phase, eligible participants underwent coronary computed tomography (CT) angiography, ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET)-CT, and echocardiography. Thereafter, participants were randomized 1:1 to colchicine 0.5 mg once daily or a matching placebo. All baseline imaging is repeated after 24 months. The primary endpoint is the change in aortic valve calcium score on CT. Secondary endpoints are (1) the change in aortic valve ¹⁸F-NaF uptake on PET-CT and corrected for target-to-background ratio, and (2) the change in peak aortic jet velocity on echocardiography. CONCLUSION: The CHIANTI trial evaluates whether anti-inflammatory therapy with low-dose colchicine can slow or halt the progression of moderate AS. If successful, it would offer the first effective pharmacological treatment for AS. TRIAL REGISTRATION: Registered on ClinicalTrials.gov (https://clinicaltrials.gov/), ID: NCT05162742.