Colchicine and Inflammation in Aortic Stenosis

Phase 3

Active, not recruiting

• Conditions: Aortic Valve Stenosis; Cardiovascular Diseases; Aortic Valve Disease; Inflammation; Aortic Valve Calcification; Calcification
• Interventions: Drug: Colchicine; Drug: Placebo

• Registration Number: NCT05162742
• Lead Sponsor: Radboud University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-16
• Study First Submitted QC: 2021-12-06
• Study First Posted: 2021-12-17
• Study Start: 2022-12-22
• Status Verified: 2024-05
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-06
• Primary Completion: 2025-12-22
• Study Completion: 2025-12-22

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Colchicine	Colchicine	75 patients will receive colchicine tablets
Placebo	Placebo	75 patients will receive placebo tablets

Primary Outcome Measures

Name	Time	Method
Change in aortic valve calcium score	Baseline and 24 months	Change in aortic valve calcium score measured by computed tomography aortic valve calcification (CT-AVC).

Secondary Outcome Measures

Name	Time	Method
Aortic valve 18F-NaF uptake	Baseline and 24 months	Difference in aortic valve 18F-NaF uptake of the aortic valve using positron emission tomography (PET) between baseline and end of study.
Change in echocardiographic parameter for aortic stenosis	Baseline, 12 months and 24 months	Determined by change in peak velocity (m/s)
Adverse Outcomes	Baseline and 24 months	Determine the effect of colchicine on calcified aortic stenosis related adverse outcomes (cardiac death, myocardial infarction, stroke, (hospitalization for) heart failure and aortic valve replacement).

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, The Netherlands, Netherlands