title: Safety and efficacy of flecainide in subjects with Long QT-3 syndrome (DeltaKPQ mutation): a randomized, double-blind, placebo-controlled clinical trial.
abstract: BACKGROUND
  We conducted a study of chronic therapy with flecainide versus placebo in a small group of LQT-3 patients with the DeltaKPQ deletion to evaluate the safety and efficacy of flecainide in this genetic disorder. In vitro studies have shown that flecainide provides correction of the impaired inactivation associated with the DeltaKPQ deletion.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled clinical trial was conducted with flecainide and placebo in six male LQT-3 subjects with the DeltaKPQ deletion.
  
  
  RESULTS
  The lowest possible dose of flecainide associated with at least a 40 ms reduction in the QTc interval was determined in an initial open-label, dose-ranging investigation using one-fourth or half of the recommended maximal antiarrhythmic flecainide dose. QTc reduction was achieved with a flecainide dose of 1.5 mg/kg per day in 4 subjects and with 3.0 mg/kg per day in 2 subjects. Subjects were randomized to four 6-month alternating periods of flecainide and placebo therapy based on the open-label dose findings. Average QTc values during placebo and flecainide therapies were 534 ms and 503 ms, respectively, with an adjusted reduction in QTc of -27.1 ms (95% confidence interval: -36.8 ms to -17.4 ms; P<0.001) at a mean flecainide blood level of 0.11+/-0.05 microg/ml. Minimal prolongation in QRS occurred (mean: +2.5 ms), and there were no major adverse cardiac effects.
  
  
  CONCLUSIONS
  Chronic low-dose flecainide significantly shortens the QTc interval in LQT-3 subjects with the DeltaKPQ mutation. No major adverse drug effects were observed with flecainide during this trial, but the sample size is not large enough to evaluate the safety of flecainide therapy in patients with this mutation.
authors.affiliation: Cardiology Unit of the Department of Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA. heartajm@heart.rochester.edu
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: John R
authors.initials: JR
authors.lastname: Windle
authors.forename: W Jackson
authors.initials: WJ
authors.lastname: Hall
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Robinson
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Patricia
authors.initials: P
authors.lastname: Severski
authors.forename: Spencer
authors.initials: S
authors.lastname: Rosero
authors.forename: James P
authors.initials: JP
authors.lastname: Daubert
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.forename: Michael
authors.initials: M
authors.lastname: Cieciorka
authors.forename: Allan S
authors.initials: AS
authors.lastname: Manalan
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005424:Flecainide / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009329:Nebraska; D009518:New York; D015990:Placebo Effect; D016896:Treatment Outcome
chemical_list: D005424:Flecainide