Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- The decrease of rate of aortic root growth measured by echocardiography at level of sinuses of Valsalva. The measure will be expressed in mm of growth per year and as Z-score.
研究概览
简要总结
To study the effect of losartan (an angiotensin receptor blocker-ARB) on aortic root growth in patients with Marfan syndrome, already treated with beta-blockers (BB). The effect of losartan will be compared to placebo. Losartan or placebo will be added to the treatment regimen in a two-step up-titration scheme over 2 weeks. Start doses of Losartan will be 25 mg for subjects under 50kg of weight and 50mg if the weight is over 50kg. Uptitration will be guided by the tolerance of the drug by the patients. Patients will be contacted by phone call for assessment of side-effects before second step of uptitration.
Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if the weight is over 50kg
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients > 10 years
- •Diagnosis of MFS, according to the Ghent criteria and/or genetically proven FBN1 mutations or linkage
- •Consent obtained (written) either for the patient and for his/her parents (<18y
- •Z-score of the aorta at the level of the sinus of Valsalva ≥2 (BSA adjusted)
- •ARB naïve patients
排除标准
- •Poor echocardiographic window,limiting the accurate measurement of the aortic root
- •Contra-indication for ARB: Bilateral renal artery stenosis, renal function abnormalities (creatinine above normal for age), hyperkalemia
- •Intolerance for ARB (eg angioedema)
- •Pregnancy or breast feeding women
- •Absence of effective contraception
- •Liver function abnormalities
- •Heart Failure
- •Patients included in other clinical trial
研究组 & 干预措施
1
Losartan
干预措施: Losartan (Drug)
2
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
The decrease of rate of aortic root growth measured by echocardiography at level of sinuses of Valsalva. The measure will be expressed in mm of growth per year and as Z-score.
时间窗: At baseline and after 6 months, 1, 2 and 3 years follow-up
次要结局
- Evaluation of progression of aortic regurgitation(At baseline and after 6 months, 1, 2 and 3 years follow-up)
- Quality of life(At baseline and after 6 months, 1, 2 and 3 years follow-up)
- Genetic polymorphisms affecting clinical symptoms and response to treatment(End of study)
- Aortic dissection incidence(At baseline and after 6 months, 1, 2 and 3 years follow-up)
- Left ventricular size and function(At baseline and after 6 months, 1, 2 and 3 years follow-up)
- Skeletal and somatic traits(At baseline and after 6 months, 1, 2 and 3 years follow-up)
- Aortic stiffness as assessed by MRI(At baseline and after 1 year and 3 years follow-up)
- Death(At baseline and after 6 months, 1, 2 and 3 years follow-up)
- Comparative arterial stiffness(At baseline and after 6 months, 1, 2 and 3 years follow-up)
- Aortic root surgery(At baseline and after 6 months, 1, 2 and 3 years follow-up)
- Progression of mitral regurgitation(At baseline and after 6 months, 1, 2 and 3 years follow-up)