Colchicine and Inflammation in Aortic Stenosis

Cardiovascular Diseases Clinical Trial

— CHIANTI  

Official title:

Does Colchicine Reduce Progression of Aortic Valve Stenosis?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05162742
• Other study ID #: 112719
• Status: Recruiting
• Phase: Phase 3
• Start date: December 22, 2022
• Est. completion date: December 22, 2025

Study information

• Verified date: May 2024
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 22, 2025
• Est. primary completion date: December 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criterion:

• 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.

Related Conditions & MeSH terms

• Aortic Valve Calcification
• Aortic Valve Disease
• Aortic Valve Stenosis
• Calcification
• Calcinosis
• Cardiovascular Diseases
• Constriction, Pathologic
• Inflammation

Intervention

Drug:
• Colchicine
ATC: M04AC01
• Placebo
Placebo tablets

Locations

Country	Name	City	State
Netherlands	Radboudumc	Nijmegen	The Netherlands

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in aortic valve calcium score	Change in aortic valve calcium score measured by computed tomography aortic valve calcification (CT-AVC).	Baseline and 24 months
Secondary	Aortic valve 18F-NaF uptake	Difference in aortic valve 18F-NaF uptake of the aortic valve using positron emission tomography (PET) between baseline and end of study.	Baseline and 24 months
Secondary	Change in echocardiographic parameter for aortic stenosis	Determined by change in peak velocity (m/s)	Baseline, 12 months and 24 months
Secondary	Adverse Outcomes	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).	Baseline and 24 months