Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

NCT ID: NCT01117454

Last Updated: 2017-06-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2015-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Catecholaminergic Polymorphic Ventricular Tachycardia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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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.

Group Type OTHER

Flecainide Acetate

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

placebo, similar in appearance to flecainide

Beta blocker

Intervention Type DRUG

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

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.

Group Type OTHER

Flecainide Acetate

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

placebo, similar in appearance to flecainide

Beta blocker

Intervention Type DRUG

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

Interventions

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Flecainide Acetate

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

Intervention Type DRUG

Placebo

placebo, similar in appearance to flecainide

Intervention Type DRUG

Beta blocker

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

5 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Prince Joseph Kannankeril

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Prince J Kannankeril, MD, MSCI

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

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University of California Los Angeles

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

Cook Children's Hospital

Fort Worth, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 19330009 (View on PubMed)

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, Haissaguerre 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.

Reference Type BACKGROUND
PMID: 21616285 (View on PubMed)

Kannankeril PJ, Moore JP, Cerrone M, Priori SG, Kertesz NJ, Ro PS, Batra AS, Kaufman ES, Fairbrother DL, Saarel EV, Etheridge SP, Kanter RJ, Carboni MP, Dzurik MV, Fountain D, Chen H, Ely EW, Roden DM, Knollmann BC. Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial. JAMA Cardiol. 2017 Jul 1;2(7):759-766. doi: 10.1001/jamacardio.2017.1320.

Reference Type BACKGROUND
PMID: 28492868 (View on PubMed)

Related Links

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Other Identifiers

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100472

Identifier Type: -

Identifier Source: org_study_id

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