CLINICAL RESEARCH: CARDIAC RHYTHM DISTURBANCES
A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation
Denis Roy, MD, FACC*,*,
Brian H. Rowe, MD, MSc ,
Ian G. Stiell, MD, MSc ,
Benoit Coutu, MD ,
John H. Ip, MD||,
Denis Phaneuf, MD¶,
Jacques Lee, MD, MSc#,
Humberto Vidaillet, MD, FACC**,
Garth Dickinson, MD,
Sheila Grant, MBA,
Alan M. Ezrin, PhD,
Gregory N. Beatch, PhD for the CRAFT Investigators
* Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada
University of Alberta, Edmonton, Alberta, Canada
University of Ottawa, Ottawa, Ontario, Canada
CHUM-Notre Dame, Montreal, Quebec, Canada
|| Cardiovascular Institute, Lansing, Michigan
¶ CHUM-Hotel-Dieu, Montreal, Quebec, Canada
# University of Toronto, Toronto, Ontario, Canada
** Marshfield Clinic, Marshfield, Wisconsin
Cardiome Pharma, Vancouver, British Colombia, Canada
Manuscript received April 30, 2004;
revised manuscript received August 19, 2004,
accepted September 3, 2004.
* Reprint requests and correspondence: Dr. Denis Roy, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada, H1T 1C8 (Email: d_roy{at}icm-mhi.com).
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.
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Abbreviations and Acronyms
| | AF = atrial fibrillation | | ECG = electrocardiogram/electrocardiographic |
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