Clinical trial NCT05162742: Colchicine and Inflammation in Aortic Stenosis
Official title: Does Colchicine Reduce Progression of Aortic Valve Stenosis?
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Aortic Valve Disease
Aortic Valve Stenosis
Aortic Valve Calcification
Inflammation
Calcification
Cardiovascular Diseases
Keywords: Aortic Stenosis
Inflammation
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2021-12-17
Enrollment: 150
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in aortic valve calcium score
timeFrame: Baseline and 24 months
Secondary outcomes:
measure: Aortic valve 18F-NaF uptake
timeFrame: Baseline and 24 months
measure: Change in echocardiographic parameter for aortic stenosis
timeFrame: Baseline, 12 months and 24 months
measure: Adverse Outcomes
timeFrame: Baseline and 24 months
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: The Netherlands
Study officials:
References: