A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation.

OBJECTIVES The purpose of this study was to determine the efficacy and safety of intravenous RSD1235 in terminating recent onset atrial fibrillation (AF). BACKGROUND Anti-arrhythmic drugs currently available to terminate AF have limited efficacy and safety. RSD1235 is a novel atrial selective anti-arrhythmic drug. METHODS This was a phase II, multi-centered, randomized, double-blinded, step-dose, placebo-controlled, parallel group study. Fifty-six patients from 15 U.S. and Canadian sites with AF of 3 to 72 h duration were randomized to one of two RSD1235 dose groups or to placebo. The two RSD1235 groups were RSD-1 (0.5 mg/kg followed by 1 mg/kg) or RSD-2 (2 mg/kg followed by 3 mg/kg), by intravenous infusion over 10 min; a second dose was given only if AF was present. The primary end point was termination of AF during infusion or within 30-min after the last infusion. Secondary end points included the number of patients in sinus rhythm at 0.5, 1, and 24 h post-last infusion and time to conversion to sinus rhythm. RESULTS The RSD-2 dose showed significant differences over placebo in: 1) termination of AF (61% vs. 5%, p < 0.0005); 2) patients in sinus rhythm at 30 min (56% vs. 5%, p < 0.001); 3) sinus rhythm at 1 h (53% vs. 5%, p = 0.0014); and 4) median time to conversion to SR (14 vs. 162 min, p = 0.016). There were no serious adverse events related to RSD1235. CONCLUSIONS RSD1235, a new atrial-selective anti-arrhythmic agent, appears to be efficacious and safe for converting recent onset AF to sinus rhythm.