A Prospective Randomized Crossover Trial of Oral Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 10
- 主要终点
- Number of Patients With Ventricular Ectopy or VT During Exercise Treadmill Testing
研究概览
简要总结
The purpose of this study is to test whether the addition of oral flecainide to standard therapy will reduce ventricular ectopy on exercise test compared to placebo plus standard therapy in patients with Catecholaminergic Polymorphic Ventricular Tachycardia.
详细描述
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a genetic arrhythmia syndrome characterized by frequent ventricular ectopy and polymorphic, classically bidirectional ventricular tachycardia with physical or emotional stress, which also carries a risk of ventricular fibrillation and sudden death, despite no structural heart abnormality. Treatment consists of beta-blockers and/or calcium channel blockers, but up to 30% of patients require implantable cardioverter-defibrillators (ICDs) due to recurrent symptoms on medical therapy. In an animal model, flecainide was found to directly target the molecular defect in CPVT. In a retrospective clinical study in patients with CPVT we have seen improvement of ventricular ectopy on exercise tests when flecainide is added to standard therapy. We propose a prospective trial of flecainide added to standard therapy in CPVT patients to test the hypothesis that flecainide will reduce ventricular ectopy on exercise testing compared to placebo plus standard therapy.
This will be a single-blind (blinded subjects) randomized cross-over study, in which each patient will receive treatment A (flecainide or placebo) for at least 3 months and, after a 1 week wash-out, treatment B (placebo or flecainide) for at least 3 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 5 Years 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of CPVT, based on:
- •A. reproducible polymorphic or bidirectional ventricular tachycardia with exercise OR B. Ventricular ectopy on exercise test with RYR2 or CASQ2 mutation
- •Functioning ICD in place
- •On stable dose of standard therapy defined as the maximal tolerated dose of beta-blocker and may include a calcium channel blocker
- •Patients on flecainide or mexiletine are also eligible for enrollment after a 1 week "washout" period during which flecainide or mexiletine is discontinued, and standard therapy alone is used.
排除标准
- •Females who are pregnant or plan to be pregnant during the study period
- •Children < 5 years of age
- •Patients unable to perform treadmill exercise
- •Patients with significant structural heart disease
- •Patients with features consistent with Andersen-Tawil syndrome A. Periodic paralysis or unexplained weakness B. Dysmorphic facies C. Known KCNJ2 mutation
- •Patients with known hypersensitivity to flecainide
- •Patients on amiodarone
- •Patients not expected to comply with follow-up
研究组 & 干预措施
Flecainide then placebo
In this crossover study, half of the subjects will be randomized to flecainide plus standard therapy with beta-blockers first, then crossover to placebo plus standard therapy with beta-blockers.
干预措施: Flecainide Acetate (Drug)
Flecainide then placebo
In this crossover study, half of the subjects will be randomized to flecainide plus standard therapy with beta-blockers first, then crossover to placebo plus standard therapy with beta-blockers.
干预措施: Placebo (Drug)
Flecainide then placebo
In this crossover study, half of the subjects will be randomized to flecainide plus standard therapy with beta-blockers first, then crossover to placebo plus standard therapy with beta-blockers.
干预措施: Beta blocker (Drug)
Placebo then flecainide
In this crossover study, half of the subjects will be randomized to placebo plus standard therapy with beta-blockers first, then crossover to flecainide plus standard therapy with beta-blockers.
干预措施: Flecainide Acetate (Drug)
Placebo then flecainide
In this crossover study, half of the subjects will be randomized to placebo plus standard therapy with beta-blockers first, then crossover to flecainide plus standard therapy with beta-blockers.
干预措施: Placebo (Drug)
Placebo then flecainide
In this crossover study, half of the subjects will be randomized to placebo plus standard therapy with beta-blockers first, then crossover to flecainide plus standard therapy with beta-blockers.
干预措施: Beta blocker (Drug)
结局指标
主要结局
Number of Patients With Ventricular Ectopy or VT During Exercise Treadmill Testing
时间窗: 3 months
Hypothesis: the addition of oral flecainide to standard therapy will reduce ventricular ectopy and/or VT on treadmill exercise treadmill testing in patients with CPVT, compared to placebo plus standard therapy.
次要结局
未报告次要终点
研究者
Prince Joseph Kannankeril
Principal Investigator
Vanderbilt University Medical Center