title: COR-ART: A multicenter, randomized, double-blind, placebo-controlled dose-ranging study to evaluate single oral doses of vanoxerine for conversion of recent-onset atrial fibrillation or flutter to normal sinus rhythm.
abstract: BACKGROUND
  Restoration of sinus rhythm (SR) in patients with atrial fibrillation/atrial flutter (AF/AFL) is limited principally to direct current cardioversion. The multi-ion channel blocker vanoxerine may prove an effective alternative.
  
  
  OBJECTIVE
  The purpose of this study was to assess vanoxerine, a 1,4-dialkylpiperazine derivative, for acute conversion of recent-onset, symptomatic AF and AFL.
  
  
  METHODS
  One hundred four subjects with symptomatic AF/AFL for <7 days were randomized sequentially to single oral doses of vanoxerine 200, 300, and 400 mg or placebo. Holter monitors were examined for conversion to SR and proarrhythmia through ≥24 hours.
  
  
  RESULTS
  Conversion to SR was dose related: 18.2%, 44.0%, and 52.0% within 4 hours, and 59.1%, 64.0%, and 84.0% within 24 hours, for the 200-, 300-, and 400-mg groups, respectively. This was significantly higher than placebo for the 300- and 400-mg groups within 4 hours (12.5% for placebo; P = .0138 and P = .0028, respectively) and for all doses within 24 hours (31.3% for placebo; P = .0421, P = .0138, P = .0001 for 200-, 300-, and 400-mg vanoxerine groups, respectively). Although vanoxerine caused significant dose-dependent QTcF (QT correction by Fridericia) prolongation, monomorphic or polymorphic ventricular tachycardia did not occur. Adverse events were mild and self-limited, with only the highest dose having a greater frequency than placebo.
  
  
  CONCLUSIONS
  Oral vanoxerine converted AF/AFL to SR at a high rate, was well tolerated, and caused no ventricular proarrhythmia.
authors: Laguna Pharmaceuticals, Inc, La Jolla, California. Electronic address: hdittrich@lagunarx.com.
authors: Howard C
authors: HC
authors: Dittrich
authors: University of California, San Diego, La Jolla, California.
authors: Gregory K
authors: GK
authors: Feld
authors: Duke University, Durham, North Carolina.
authors: Tristram D
authors: TD
authors: Bahnson
authors: St. George's University of London, London, England.
authors: A John
authors: AJ
authors: Camm
authors: Russian Cardiologic Research and Production Complex of Rosmedtechnologiy, Moscow, Russia.
authors: Sergey
authors: S
authors: Golitsyn
authors: Barzilai Medical Center, Ashkelon, Israel.
authors: Amos
authors: A
authors: Katz
authors: Duke University, Durham, North Carolina.
authors: Jason I
authors: JI
authors: Koontz
authors: Jefferson Medical College, Philadelphia, Pennsylvania.
authors: Peter R
authors: PR
authors: Kowey
authors: University Hospital Cleveland, Cleveland, Ohio.
authors: Albert L
authors: AL
authors: Waldo
authors: Laguna Pharmaceuticals, Inc, La Jolla, California.
authors: Arthur M
authors: AM
authors: Brown
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001282:Atrial Flutter / Q000188:drug therapy*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D004554:Electric Countershock; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011446:Prospective Studies
chemical_list: D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; C043425:vanoxerine
keywords: Arrhythmia; Atrial fibrillation; Atrial flutter; Cardioversion; Vanoxerine