Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

• 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.
  
  

• 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.
  
  

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.