Colchicine and Inflammation in Aortic Stenosis

NCT05162742 | Active Not Recruiting Phase 3

• 1 other identifier: 112719
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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

Keywords

Aortic Stenosis; Inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Aortic valve 18F-NaF uptake

  Baseline and 24 months

• Change in echocardiographic parameter for aortic stenosis

  Baseline, 12 months and 24 months

• Adverse Outcomes

  Baseline and 24 months

Study Arms (2)

Colchicine

ACTIVE COMPARATOR

75 patients will receive colchicine tablets

Drug: Colchicine

Placebo

PLACEBO COMPARATOR

75 patients will receive placebo tablets

Drug: Placebo

Interventions

Colchicine DRUG

ATC: M04AC01

Colchicine

Placebo DRUG

Placebo tablets

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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);

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboudumc

Nijmegen, The Netherlands, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 40659197 DERIVED

MeSH Terms

Conditions

Aortic Valve Disease; Aortic Valve Stenosis; Aortic Valve, Calcification of; Inflammation; Calcinosis; Cardiovascular Diseases

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Ventricular Outflow Obstruction; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: December 17, 2021
• Study Start: December 22, 2022
• Primary Completion: December 22, 2025
• Study Completion: December 22, 2025
• Last Updated: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)