Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

NCT01117454 | Completed Results DMC

• 1 other identifier: 100472
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Catecholaminergic Polymorphic Ventricular Tachycardia

Keywords

Catecholaminergic Polymorphic Ventricular Tachycardia; implantable cardioverter-defibrillator; flecainide

Outcome Measures

Primary Outcomes (1)

• 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.

  3 months

Study Arms (2)

Flecainide then placebo

OTHER

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.

Drug: Flecainide Acetate; Drug: Placebo; Drug: Beta blocker

Placebo then flecainide

OTHER

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.

Drug: Flecainide Acetate; Drug: Placebo; Drug: Beta blocker

Interventions

Flecainide Acetate DRUG

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

Flecainide then placebo; Placebo then flecainide

Placebo DRUG

placebo, similar in appearance to flecainide

Flecainide then placebo; Placebo then flecainide

Beta blocker DRUG

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

Flecainide then placebo; Placebo then flecainide

Eligibility Criteria

• Age: 5 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Functioning ICD in place
• 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.

You may not qualify if:

• Females who are pregnant or plan to be pregnant during the study period
• Children \< 5 years of age
• Patients unable to perform treadmill exercise
• Patients with significant structural heart disease
• Patients with features consistent with Andersen-Tawil syndrome A. Periodic paralysis or unexplained weakness B. Dysmorphic facies C. Known KCNJ2 mutation
• Patients with known hypersensitivity to flecainide
• Patients on amiodarone
• Patients not expected to comply with follow-up

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (10)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

NYU Langone Medical Center

New York, New York, 10010, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Vanderbilt University

Nashville, Tennessee, 37027, United States

Location

Cook Children's Hospital

Fort Worth, Texas, 76104, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (3)

• 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.

  PMID: 19330009 BACKGROUND

• 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.

  PMID: 21616285 BACKGROUND

• 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.

  PMID: 28492868 BACKGROUND

Related Links

• Full text of publication in JAMA Cardiology

MeSH Terms

Conditions

Polymorphic Catecholaminergic Ventricular Tachycardia

Interventions

Flecainide; Adrenergic beta-Antagonists

Condition Hierarchy (Ancestors)

Tachycardia, Ventricular; Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Results Point of Contact

• Title: Dr. Prince J. Kannankeril, MD, MSCI
• Organization: Vanderbilt University Medical Center

prince.kannankeril@vanderbilt.edu

615 322-7447

Study Officials

• Prince J Kannankeril, MD, MSCI

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 4, 2010
• First Posted: May 5, 2010
• Study Start: December 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: June 14, 2017
• Results First Posted: May 17, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)