title: Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter.
abstract: OBJECTIVE
  The goal of the present study was to assess the efficacy and safety of intravenous tedisamil, a new antiarrhythmic compound, for conversion of recent-onset atrial fibrillation (AF) or atrial flutter (AFL) to normal sinus rhythm (NSR).
  
  
  BACKGROUND
  Tedisamil is a novel antiarrhythmic drug with predominantly class III activity. Its efficacy and safety for conversion of recent onset AF or AFL to NSR is not known.
  
  
  METHODS
  This was a multicenter, double-blind, randomized, placebo-controlled, sequential ascending dose-group trial. A total of 201 patients with symptomatic AF or AFL of 3 to 48 h duration were enrolled in a two-stage study. During stage 1, patients were randomized to receive tedisamil at 0.4 mg/kg body weight or matching placebo; during stage 2, patients received tedisamil at 0.6 mg/kg body weight or matching placebo. Treatments were given as single intravenous infusions. The primary study end point consisted of the percentage of patients converting to NSR for at least 60 s within 2.5 h.
  
  
  RESULTS
  Of 175 patients representing the intention-to-treat sample, conversion to NSR was observed in 41% (25/61) of the tedisamil 0.4 mg/kg group, 51% (27 of 53) of the tedisamil 0.6 mg/kg group, and 7% (4/59) of the placebo group (p < 0.001 for both tedisamil groups vs. placebo). Average time to conversion was 35 min in patients receiving tedisamil. There were two instances of self-terminating ventricular tachycardia: one episode of torsade de pointes and one of monomorphic ventricular tachycardia, both in patients receiving 0.6 mg/kg tedisamil.
  
  
  CONCLUSIONS
  Tedisamil at dosages of 0.4 and 0.6 mg/kg was superior to placebo in converting AF or AFL. Tedisamil has a rapid onset of action leading to conversion within 30 to 40 min in the majority of responders.
authors.affiliation: Department of Cardiology, Division of Electrophysiology, J. W. Goethe University, Frankfurt, Germany. hohnloser@em.uni-frankfurt.de
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
authors.forename: Matthias
authors.initials: M
authors.lastname: Straub
authors.forename: Katrin
authors.initials: K
authors.lastname: Beckmann
authors.forename: Peter
authors.initials: P
authors.lastname: Kowey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D001282:Atrial Flutter / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003521:Cyclopropanes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004554:Electric Countershock; D004562:Electrocardiography; D023381:Endpoint Determination; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; C059921:tedisamil