Aortic stenosis (AS) is the most common valvular heart disease in the developed world. The prevalence of aortic sclerosis in the general population is estimated to be 25% at the age of 65 years and severe aortic stenosis is present in 10-15% of the patients aged > 75 years. Once symptomatic, untreated patients have a poor prognosis with a five-year survival rate of 25%. There is no effective medical therapy to stop progression of AS.
Conditions
Interventions
Trade Name: Colchicine
Product Name: Colchicine
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Radboudumc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Asymptomatic moderate aortic valve stenosis on recent (=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
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. (see Appendix 1). • Severe mitral valve stenosis (MVA 80 years. • Pre-existing chronic gastro-intestinal complaints which may obscure signs of colchicine intolerance. • The presence of a pacemaker or internal cardiac defibrillator. • Child-bearing potential without the use of contraception. • Renal impairment (eGFR <30 ml/min/1.73m2). • Active or chronic liver disease. • A planned aortic valve replacement in the next six months. • 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). • Life expectancy <2 years.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to determine the effect of colchicine on the progression of moderate AS in asymptomatic patients.;Secondary Objective: •To determine the effect of colchicine treatment on aortic valve 18F-NaF uptake as a measure of aortic valve calcification activity. •To study the effect of colchicine treatment on the progression of aortic valve stenosis measured with echocardiography. ;Primary end point(s): Change in aortic valve calcium score measured by computed tomography aortic valve calcification (CT-AVC);Timepoint(s) of evaluation of this end point: 24 months after start treatment with colchicine/placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Difference in aortic valve 18F-NaF uptake of the aortic valve using positron emission tomography (PET) between baseline and end of study. Change in peak velocity (m/s) measured by echocardiography for aortic valve stenosis.;Timepoint(s) of evaluation of this end point: 24 months after start treatment with colchicine/placebo | — |
Countries
Netherlands
Contacts
Public ContactDepartment of Cardiology
Radboudumc
Outcome results
None listed