This study has been transitioned to CTIS with ID 2024-513486-39-00 check the CTIS register for the current data. The main objective of this study is to determine the effect of colchicine on the progression of moderate AS in asymptomatic patients.
ID
Source
Brief title
Condition
- Cardiac valve disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change at 24 months relative to baseline in:
- Aortic valve calcium score measured by computed tomography (Agatston Units).
Secondary outcome
The change at 24 months relative to baseline in:
- 18F-NaF uptake of the aortic valve using positron emission tomography (PET).
- Peak aortic-jet velocity (m/s determined by echocardiography).
Background 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
moderate AS.
Study objective
This study has been transitioned to CTIS with ID 2024-513486-39-00 check the CTIS register for the current data.
The main objective of this study is to determine the effect of colchicine on
the progression of moderate AS in asymptomatic patients.
Study design
This study will be a double-blind placebo controlled intervention study, with
prior to randomization an open label two-week run-in period.
Intervention
colchicine vs placebo
Study burden and risks
Patients will undergo CCTA, NaF-PET-CT and echocardiography. The CCTA and
NaF-PET-CT will be performed at baseline and after 24 months. Echocardiography
will be performed at baseline, 12 months and 24 months. Clinical evaluation
will be conducted at baseline, 3 months, 6 months and every six months after.
Colchicine has been proven to be safe in use. Potential side-effects mostly
include gastro-intestinal symptoms. The echocardiographies for this study will
replace the echocardiographies needed for usual-care follow-up in AS. This will
decrease the burden of participation. We believe that this study has relative
low burden for participants with potentially high benefit in a relative vital
study group. See also chapter 12 of the study protocol.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- Asymptomatic moderate aortic valve stenosis. 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.).
• Severe mitral valve stenosis (MVA < 1cm2).
• Severe mitral or aortic valve regurgitation.
• Left ventricular dysfunction (LVEF < 35%).
• Bicuspid aortic valve.
• Rheumatic aortic valve disease.
• Valvular disease due to history of chest radiation.
• Patients aged <50 and >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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-513486-39-00 |
| EudraCT | EUCTR2021-005586-40-NL |
| ClinicalTrials.gov | NCT05162742 |
| CCMO | NL79407.091.21 |