Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic Polymorphic Ventricular Tachycardia Clinical Trial

Official title:

A Prospective Randomized Crossover Trial of Oral Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01117454
• Other study ID #: 100472
• Status: Completed
• Phase: N/A
• First received: May 4, 2010
• Last updated: February 11, 2016
• Start date: December 2011
• Est. completion date: December 2015

Study information

• Verified date: February 2016
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 99 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Catecholaminergic Polymorphic Ventricular Tachycardia
• Tachycardia
• Tachycardia, Ventricular

Intervention

Drug:
• flecainide
oral flecainide will be added to standard therapy with the dose titrated to achieve a serum level between 0.5-0.8 mcg/ml

Locations

Country	Name	City	State
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Duke University	Durham	North Carolina
United States	Cook Children's Hospital	Fort Worth	Texas
United States	East Carolina University	Greenville	North Carolina
United States	University of California Los Angeles	Los Angeles	California
United States	Vanderbilt University	Nashville	Tennessee
United States	NYU Langone Medical Center	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

References & Publications (2)

van der Werf C, Kannankeril PJ, Sacher F, Krahn AD, Viskin S, Leenhardt A, Shimizu W, Sumitomo N, Fish FA, Bhuiyan ZA, Willems AR, van der Veen MJ, Watanabe H, Laborderie J, Haïssaguerre M, Knollmann BC, Wilde AA. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol. 2011 May 31;57(22):2244-54. doi: 10.1016/j.jacc.2011.01.026. — View Citation

Watanabe H, Chopra N, Laver D, Hwang HS, Davies SS, Roach DE, Duff HJ, Roden DM, Wilde AA, Knollmann BC. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med. 2009 Apr;15(4):380-3. doi: 10.1038/nm.1942. Epub 2009 Mar 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ventricular ectopy and 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.	5 years	No