Aortic Valve Calcification, Aortic Valve Disease, Aortic Valve Stenosis, Calcification, Cardiovascular Diseases, Inflammation
Conditions
Keywords
Aortic Stenosis, Inflammation
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.
Interventions
DRUGColchicine
ATC: M04AC01
DRUGPlacebo
Placebo tablets
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in aortic valve calcium score | Baseline and 24 months | Change in aortic valve calcium score measured by computed tomography aortic valve calcification (CT-AVC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aortic valve 18F-NaF uptake | Baseline and 24 months | Difference in aortic valve 18F-NaF uptake of the aortic valve using positron emission tomography (PET) between baseline and end of study. |
| Change in echocardiographic parameter for aortic stenosis | Baseline, 12 months and 24 months | Determined by change in peak velocity (m/s) |
| Adverse Outcomes | Baseline and 24 months | 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). |
Countries
Netherlands
Outcome results
None listed