Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Prince Joseph Kannankeril, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01117454
First received: May 4, 2010
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to test whether the addition of oral flecainide to standard therapy will reduce cardiac events compared to placebo plus standard therapy in patients with Catecholaminergic Polymorphic Ventricular Tachycardia.


Condition Intervention
Catecholaminergic Polymorphic Ventricular Tachycardia
Drug: flecainide

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Prospective Randomized Crossover Trial of Oral Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • VT treated by ICD or death [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Hypothesis: the addition of oral flecainide to standard therapy will reduce cardiac events compared to placebo plus standard therapy, in patients with CPVT.


Secondary Outcome Measures:
  • ventricular ectopy and VT during exercise treadmill testing [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.

  • association of ventricular ectopy and VT during exercise treadmill testing with cardiac events [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Hypothesis: the degree of ventricular ectopy and VT during exercise treadmill testing will correlate with cardiac events regardless of therapy in CPVT.


Estimated Enrollment: 60
Study Start Date: December 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Flecainide then placebo
In this crossover study, half of the subjects will be randomized to flecainide plus standard therapy for the first 18 months, then crossover to placebo plus standard therapy for 18 months. An ICD shock will result in early crossover.
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
Placebo then flecainide
In this crossover study, half of the subjects will be randomized to placebo plus standard therapy for the first 18 months, then crossover to flecainide plus standard therapy for 18 months. An ICD shock will result in early crossover.
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

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 5 year prospective trial of flecainide added to standard therapy in CPVT patients with ICD's in place to test the hypothesis that flecainide will reduce ICD shocks in patients with CPVT, compared to placebo.

This will be a single-blind (blinded subjects) randomized cross-over study, in which each patient will receive treatment A (flecainide or placebo) for 18 months and, after a 1 week wash-out, treatment B (placebo or flecainide) for 18 months. The event rate and time to event will be assessed during each treatment period. Any events that occur during treatment A will result in early crossover to treatment B after 1 week of wash-out. Any events during treatment B will result in the end of the study for that subject.

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01117454

Locations
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
Children's Hospital of Orange County
Orange, California, United States, 92868
United States, Colorado
The Children's Hospital/University of Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Illinois
Advocate Health Care
Park Ridge, Illinois, United States, 60068
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, New York
NYU Langone Medical Center
New York, New York, United States, 10010
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
East Carolina University
Greenville, North Carolina, United States, 27834
United States, Ohio
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37027
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53706
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Prince J Kannankeril, MD, MSCI Vanderbilt University
  More Information

Publications:
Responsible Party: Prince Joseph Kannankeril, Principal Investigator, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01117454     History of Changes
Other Study ID Numbers: 100472
Study First Received: May 4, 2010
Last Updated: August 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Catecholaminergic Polymorphic Ventricular Tachycardia
implantable cardioverter-defibrillator
flecainide

Additional relevant MeSH terms:
Tachycardia
Tachycardia, Ventricular
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Flecainide
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014