Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
Information source: Vanderbilt University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Catecholaminergic Polymorphic Ventricular Tachycardia
Intervention: flecainide (Drug)
Phase: N/A
Status: Active, not recruiting
Sponsored by: Vanderbilt University Official(s) and/or principal investigator(s): Prince J Kannankeril, MD, MSCI, Principal Investigator, Affiliation: Vanderbilt University
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.
Clinical Details
Official title: A Prospective Randomized Crossover Trial of Oral Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Primary outcome: ventricular ectopy and VT during exercise treadmill testing
Detailed 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.
Eligibility
Minimum age: 5 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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 and Contacts
University of California Los Angeles, Los Angeles, California 90095, United States
Children's Hospital of Orange County, Orange, California 92868, United States
NYU Langone Medical Center, New York, New York 10010, United States
Duke University, Durham, North Carolina 27705, United States
East Carolina University, Greenville, North Carolina 27834, United States
MetroHealth Medical Center, Cleveland, Ohio 44109, United States
Nationwide Children's Hospital, Columbus, Ohio 43205, United States
Vanderbilt University, Nashville, Tennessee 37027, United States
Cook Children's Hospital, Fort Worth, Texas 76104, United States
University of Utah, Salt Lake City, Utah 84112, United States
Additional Information
Related publications: 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. 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.
Starting date: December 2011
Last updated: June 4, 2015
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