Colchicine and Inflammation in Aortic Stenosis

NCT ID: NCT05162742

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-22
• Study Completion Date: 2025-12-22

Brief Summary

Aortic stenosis (AS) is the most common valvular heart disease in the developed world. Once symptomatic, untreated patients have a poor prognosis with five-year survival rate of 25%. Once at an advanced stage, AS will lead to the development of left ventricle hypertrophy, and eventually heart failure and death. At-present, there is no effective medical therapy for aortic stenosis. Current management of patients with AS consists of 'watchful waiting'. Valve replacement is needed when these patients (often acutely) become symptomatic. Recent studies have shown that inflammatory processes with similarities to atherosclerosis play an important role in AS. Therefore, we hypothesize that treatment with anti-inflammatory therapy, in the form of colchicine, could reduce the progression of AS. If positive, this trial will be the first to provide a potential therapeutic option for millions of people world-wide with AS.

Conditions

Aortic Valve Disease; Aortic Valve Stenosis; Aortic Valve Calcification; Inflammation; Calcification; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Colchicine

75 patients will receive colchicine tablets

Group Type: ACTIVE_COMPARATOR

Colchicine

Intervention Type: DRUG

ATC: M04AC01

Placebo

75 patients will receive placebo tablets

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets

Interventions

Colchicine

ATC: M04AC01

Intervention Type: DRUG

Placebo

Placebo tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Asymptomatic moderate aortic valve stenosis on recent (<6 months) echocardiography (based on peak velocity, mean gradient, aortic valve area). The severity of AS will be quantified according to current EACVI / ASE guidelines.

Exclusion Criteria

• Heavily calcified aortic valve on echocardiography (defined as grade 4 calcification: extensive thickening/calcification of all cusps as described in the articles by Rosenhek et al.);
• a planned aortic valve replacement in the next six months;
• severe mitral valve stenosis (MVA < 1cm2);
• severe mitral or aortic valve regurgitation;
• rheumatic aortic valve disease;
• bicuspid aortic valve;
• valvular disease due to history of chest radiation;
• left ventricular dysfunction (LVEF < 35%);
• renal impairment (eGFR <30 ml/min/1.73m2);
• patients aged <50 and >80 years;
• pre-existing chronic gastro-intestinal complaints which may obscure signs of colchicine intolerance;
• child-bearing potential without the use of contraception;
• use of CYP3A4 (e.g. verapamil) or P-glycoprotein inhibitors;
• use of bisphosphonate or denosumab;
• chronic use of immunosuppressants or anti-inflammatory drugs including colchicine and NSAID's (excl. acetylsalicylic acid);
• active or chronic liver disease;
• the presence of a pacemaker or internal cardiac defibrillator;
• life expectancy <2 years.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Radboudumc

Nijmegen, The Netherlands, Netherlands

Countries

Netherlands

References

Mohammadnia N, Vestjens LTW, Craig NJ, Tijssen JGP, Knol RJJ, Lazarenko SV, Duffels MGJ, Jaspers Focks J, Hemels MEW, Oving I, Schalkx HJ, Eikelboom JW, Cetinyurek-Yavuz A, Aarntzen EHJG, Dey D, Slomka PJ, Nijveldt R, Riksen NP, van Royen N, Honigberg MC, Dweck MR, Cornel JH, El Messaoudi S. 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. Am Heart J. 2025 Dec;290:297-309. doi: 10.1016/j.ahj.2025.07.010. Epub 2025 Jul 12.

Reference Type: DERIVED

PMID: 40659197 (View on PubMed)

Other Identifiers

112719

Identifier Type: -

Identifier Source: org_study_id