Colchicine and Inflammation in Aortic Stenosis (CHIANTI)

Does Colchicine Reduce Progression of Aortic Valve Stenosis?

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Inflammation; Aortic Valve Stenosis; Aortic Valve Disease; Aortic Valve Calcification; Calcification
• Intervention / Treatment: Drug: Placebo; Drug: Colchicine

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • The Netherlands
    • Nijmegen, The Netherlands, Netherlands
      • Recruiting
      • Radboudumc
      • Contact: Saloua El Messaoudi, MD, PhD; Phone Number: +31(0)24 3616785; Email: onderzoek.cardio@radboudumc.nl
      • Principal Investigator: Saloua El Messaoudi, MD, PhD
      • Sub-Investigator: Nieky Mohammadnia, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Colchicine; 75 patients will receive colchicine tablets	Drug: Colchicine; ATC: M04AC01
Placebo Comparator: Placebo; 75 patients will receive placebo tablets	Drug: Placebo; Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in echocardiographic parameter for aortic stenosis	Determined by change in peak velocity (m/s)	Baseline, 12 months and 24 months
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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Anticipated): December 22, 2025
• Study Completion (Anticipated): December 22, 2025

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: January 8, 2023
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; Aortic Stenosis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Metabolic Diseases; Pathological Conditions, Anatomical; Heart Valve Diseases; Ventricular Outflow Obstruction; Calcium Metabolism Disorders; Cardiovascular Diseases; Inflammation; Aortic Valve Stenosis; Constriction, Pathologic; Aortic Valve Disease; Calcinosis; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 112719

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No