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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: September 22, 2014
Last verified: September 2014

May 4, 2010
September 22, 2014
December 2011
December 2015   (final data collection date for primary outcome measure)
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.
To assess the efficacy of flecainide in reducing cardiac events in CPVT [ Time Frame: 3 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.

Cardiac event defined as: VT treated by ICD or death

Complete list of historical versions of study NCT01117454 on ClinicalTrials.gov Archive Site
  • 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.
  • To assess the efficacy of flecainide in reducing ventricular ectopy and VT during exercise treadmill testing in CPVT [ Time Frame: 3 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.
  • To correlate ventricular ectopy and VT during exercise treadmill testing with cardiac events in CPVT [ Time Frame: 3 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.
Not Provided
Not Provided
 
Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
A Prospective Randomized Crossover Trial of Oral Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Catecholaminergic Polymorphic Ventricular Tachycardia
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
  • 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.
    Intervention: Drug: flecainide
  • 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.
    Intervention: Drug: flecainide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Enrolling by invitation
15
December 2016
December 2015   (final data collection date for primary outcome measure)

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
Both
5 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01117454
100472
Yes
Prince Joseph Kannankeril, Vanderbilt University
Vanderbilt University
Not Provided
Principal Investigator: Prince J Kannankeril, MD, MSCI Vanderbilt University
Vanderbilt University
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP