MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies (MEKinRAS) - Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Effectiveness of the trametynib treatment on cardiac hyperthropy
研究概览
简要总结
The goal of this study is to evaluate the effectiveness of trametinib treatment in patients with Hyperthropic cardiomyopathy and a genetic mutation in the RAS/MAPK pathway.
详细描述
Introduction RASopathies are a group of genetic diseases caused by mutations in the mitogen-activated kinase (RAS-MAPK) pathway. These mutations affect many processes and are the cause of numerous genetic syndromes (including Noonan syndrome) in the course of which severe hypertrophic cardiomyopathy (HCM) develops. MEK kinase inhibitors are used to treat cancers with mutations in the RAS-MAPK pathway in adults. So far, single cases of HCM treatment in patients with RASopathies have been described, with rapid improvement in both laboratory and echocardiographic parameters and regression of myocardial hypertrophy. Due to the described effectiveness, it is reasonable to verify these effects in a well-designed randomized study on a large group of patients.
Objective To evaluate the effectiveness of trametinib treatment in patients with HCM and a genetic mutation in the RAS/MAPK pathway.
Methodology
Randomized, open-label study. The study will include patients aged 0 to 18 with:
- mutation in the RAS/MAPK pathway confirmed by genetic tests
- HCM diagnosed by echocardiography
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
- None
入排标准
- 年龄范围
- 1 Day 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patient with diagnosed RASopathy
- •patient with diagnosed hypertrophic cardiomyopathy
- •signed innform consent
排除标准
- •contraindications to treatment with propranolol (drug hypersensitivity, atrioventricular block, severe bradycardia) disopyramide (drug hypersensitivity, WPW syndrome, atrioventricular block, QT prolongation) trametinib (drug hypersensitivity)
- •lack of consent of the child's guardians to participate in the study
研究组 & 干预措施
Trametynib
Trametynib in 0,025mg/kg dose orally once daily
干预措施: Trametinib tablet (Drug)
Standard therapy
Disopiramide and Beta-blocker orally
干预措施: Standard therapy (Drug)
结局指标
主要结局
Effectiveness of the trametynib treatment on cardiac hyperthropy
时间窗: 1 year
Reduction of cardiac hypertrophy and/or LVOTO at 6 and 12 months of treatment and at 3 months of follow-up after treatment discontinuation using echocardiographic examination.
Effectiveness of the trametynib treatment on laboratory enzymes levels
时间窗: 1 year
Decrease in cardiac enzyme levels (NT-pro-BNP and high-sensitivity troponin I) determined in the 6th and 12th month of treatment and in the 3rd month of observation after its discontinuation.
次要结局
- MEK kinase activity(6 months)
- Effectivness of the trametynib treatment assessed in the cardia magnetic resonance(1 year)