Colchicine and Inflammation in Aortic Stenosis

Brief Title

Colchicine and Inflammation in Aortic Stenosis

Official Title

Does Colchicine Reduce Progression of Aortic Valve Stenosis?

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.

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Change in aortic valve calcium score

Secondary Outcome

 Aortic valve 18F-NaF uptake

Condition

Aortic Valve Disease

Intervention

Colchicine

Study Arms / Comparison Groups

 Colchicine

Description:  75 patients will receive colchicine tablets

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

June 15, 2022

Completion Date

May 1, 2025

Primary Completion Date

May 1, 2025

Eligibility Criteria

        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.

Gender

All

Ages

50 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

, ,

Location Countries

Netherlands

Location Countries

Netherlands

Administrative Informations

NCT ID

NCT05162742

Organization ID

Responsible Party

Sponsor

Study Sponsor

Radboud University Medical Center

Study Sponsor

, ,

Verification Date

November 2021