Does Colchicine Reduce Progression of Aortic Valve Stenosis?
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change in aortic valve calcium score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Colchicine
75 patients will receive colchicine tablets
干预措施: Colchicine (Drug)
Placebo
75 patients will receive placebo tablets
干预措施: Placebo (Drug)
结局指标
主要结局
Change in aortic valve calcium score
时间窗: Baseline and 24 months
Change in aortic valve calcium score measured by computed tomography aortic valve calcification (CT-AVC).
次要结局
- Aortic valve 18F-NaF uptake(Baseline and 24 months)
- Change in echocardiographic parameter for aortic stenosis(Baseline, 12 months and 24 months)
- Adverse Outcomes(Baseline and 24 months)