Pilot Randomized Trial With Flecainide in ARVC Patients

University of Rochester6 个研究点分布在 1 个国家目标入组 22 人2019年7月23日

概览

简要总结

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited arrhythmia disorder with high risk of ventricular tachycardia or fibrillation, and implantable cardioverter defibrillator remains as therapy of choice. Antiarrhythmic therapy with different agents including beta-blockers, sotalol and amiodarone are usually not effective in reducing risk of arrhythmic events. Recent data indicated that flecainide effectively prevented the arrhythmias observed in the experimental ARVC animals and in small series of ARVC patients. These observations provide a strong rationale for conducting a pilot randomized clinical trial to determine whether flecainide will reduce ventricular arrhythmias in high-risk ARVC patients. This pilot study is designed as randomized double-blinded placebo-controlled crossover trial with administration of 100 mg of Flecainide or matching placebo twice a day for 4 weeks each with a washout period.

Primary specific aim of this pilot trial is to determine whether Flecainide administration is associated with a significant reduction of number of ventricular ectopic beats (VEBs) in ARVC patients with implantable cardioverter-defibrillator (ICD).

详细描述

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited arrhythmia disorder with high risk of ventricular tachycardia or fibrillation, and implantable cardioverter defibrillator remains as therapy of choice. Antiarrhythmic therapy with different agents including beta-blockers, sotalol and amiodarone are usually not effective in reducing risk of arrhythmic events. Recent data indicated that flecainide effectively prevented the arrhythmias observed in the experimental ARVC animals and in small series of ARVC patients. These observations provide a strong rationale for conducting a pilot randomized clinical trial to determine whether flecainide will reduce ventricular arrhythmias in high-risk ARVC patients. This pilot study is designed as randomized double-blinded placebo-controlled crossover trial with administration of 100 mg of Flecainide or matching placebo twice a day for 4 weeks each with a washout period. Primary specific aim of this pilot trial is to determine whether Flecainide administration is associated with a significant reduction of number of ventricular ectopic beats (VEBs) in ARVC patients with implantable cardioverter-defibrillator (ICD). Secondary specific aims are: 1. to assess safety of flecainide administration with particular emphasis on proarrhythmic response measured by: 1. VEBs on ECG monitoring, 2. nonsustained and sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) episodes documented on ICD interrogation, and 3. effects of Flecainide on QRS morphology and duration. 2. to assess effects of flecainide on burden of VT runs in 7-day ECG recordings. 3. to assess effects of flecainide on burden of atrial premature beats in 7-day recordings. 4. to demonstrate feasibility of enrollment of rare inherited arrhythmia ARVC patients in a randomized study in the light of planned future large clinical trial with VT/VF/death as endpoint. Study population will include 38 ARVC patients diagnosed with the 2010 ARVC Task Force Criteria who are at least 18 years old, have implanted ICD, and show at least 500 VEBs in a 24-hour Holter recording. Patients on other pharmacological antiarrhythmic treatment other than beta-blockers and patients with prior catheter VT ablation will be excluded.

注册库

clinicaltrials.gov

开始日期

2019年7月23日

结束日期

2022年7月31日

最后更新

去年

研究类型

Interventional

研究设计

Crossover

性别

All

研究者

发起方

University of Rochester

责任方

Principal Investigator

主要研究者

Wojciech Zareba

Professor of Medicine/Cardiology

University of Rochester

入排标准

入选标准

•Age \> 18 years.
•Subjects who have been diagnosed with ARVC and meet 2010 Modified Task Force Criteria for ARVC as affected.
•At minimum 500 VEBs on the most recent 24-hour Holter monitor recording prior to consent or after consent if a subsequent recording is required after 5 day washout following discontinuation of anti-arrhythmic medication.
•Functioning implanted cardioverter defibrillator with remote interrogation capability.
•Subjects should be on a beta-blocker including metoprolol, propranolol, atenolol, nadolol, carvedilol or bisoprolol unless contraindication to beta-blockers exists.
•Persons prescribed quinidine, procainamide, propafenone, disopyramide, dronedarone phenytoin, mexiletene, flecainide, may be included after 5 day washout period with subsequent 24 Hour Holter obtained after washout period.
•Persons prescribed sotalol must be included after 5 day washout period during which another beta-blocker may be administered with subsequent 24 Hour Holter obtained.
•Subject and personal physician and or cardiologist must agree not to use any antiarrhythmic medications during the 10 weeks of participation, unless needed for management of life-threatening arrhythmias.
•All subjects must agree to use medically acceptable contraceptive measures during participation unless documented as surgically sterile or post-menopausal (no menstrual periods for more than one year).

排除标准

•Prescribed amiodarone or dofetilide at the time of consent.
•Left ventricular ejection fraction ≤40% by any imaging modality: echocardiography, angiography, cardiac magnetic resonance imaging (CMRI), or cardiac nuclear test on the most recent test.
•New York Heart Association (NYHA) heart failure class III or IV at time of consent.
•Prior myocardial infarction at any time in the past.
•Pacemaker dependent rhythm at the time of consent.
•Renal impairment (GFR \<30 mL/min/m2).
•Prior diagnosis of severe hepatic impairment.
•Pregnant or plan to become pregnant during the course of the trial (Flecainide has not been adequately studied in pregnant women). Pregnancy test is required for women of child-bearing potential prior to randomization.
•Participating in any other interventional clinical trial.
•Unwilling or unable to cooperate with the protocol.