Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

Vanderbilt University Medical Center14 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Catecholaminergic Polymorphic Ventricular Tachycardia

Interventions

Flecainide AcetateDRUG

oral flecainide with the dose titrated to achieve a serum level between 0.5-0.8 mcg/ml

PlaceboDRUG

placebo, similar in appearance to flecainide

Beta blockerDRUG

Standard therapy with beta-blocker (nadolol, atenolol, metoprolol, or propranolol) continues throughout the trial.

Eligibility

Sex: ALLMin age: 5 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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 2. Functioning ICD in place 3. 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. Exclusion Criteria: 1. Females who are pregnant or plan to be pregnant during the study period 2. Children \< 5 years of age 3. Patients unable to perform treadmill exercise 4. Patients with significant structural heart disease 5. Patients with features consistent with Andersen-Tawil syndrome A. Periodic paralysis or unexplained weakness B. Dysmorphic facies C. Known KCNJ2 mutation 6. Patients with known hypersensitivity to flecainide 7. Patients on amiodarone 8. Patients not expected to comply with follow-up

Locations (10)

University of California Los Angeles

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

NYU Langone Medical Center

New York, New York, United States

Outcomes

Primary Outcomes

Number of Patients With Ventricular Ectopy or VT During Exercise Treadmill Testing

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.

Time frame: 3 months

Data from ClinicalTrials.gov

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