HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Roy, D. Search for Related Content PubMed PubMed Citation Articles by Roy, D.

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.

Abbreviations and Acronyms   AF = atrial fibrillation   ECG = electrocardiogram/electrocardiographic

This article has been cited by other articles:

				I. Savelieva and J. Camm Anti-arrhythmic drug therapy for atrial fibrillation: current anti-arrhythmic drugs, investigational agents, and innovative approaches Europace, June 1, 2008; 10(6): 647 - 665. [Abstract] [Full Text] [PDF]

				J. W. Cheng Vernakalant in the Management of Atrial Fibrillation Ann. Pharmacother., April 1, 2008; 42(4): 533 - 542. [Abstract] [Full Text] [PDF]

				D. Roy, C. M. Pratt, C. Torp-Pedersen, D. G. Wyse, E. Toft, S. Juul-Moller, T. Nielsen, S. L. Rasmussen, I. G. Stiell, B. Coutu, et al. Vernakalant Hydrochloride for Rapid Conversion of Atrial Fibrillation: A Phase 3, Randomized, Placebo-Controlled Trial Circulation, March 25, 2008; 117(12): 1518 - 1525. [Abstract] [Full Text] [PDF]

				J. R. Ehrlich, P. Biliczki, S. H. Hohnloser, and S. Nattel Atrial-Selective Approaches for the Treatment of Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 787 - 792. [Abstract] [Full Text] [PDF]

				J. Eldstrom, Z. Wang, H. Xu, M. Pourrier, A. Ezrin, K. Gibson, and D. Fedida The Molecular Basis of High-Affinity Binding of the Antiarrhythmic Compound Vernakalant (RSD1235) to Kv1.5 Channels Mol. Pharmacol., December 1, 2007; 72(6): 1522 - 1534. [Abstract] [Full Text] [PDF]

				B. N. Singh and E. Aliot Newer antiarrhythmic agents for maintaining sinus rhythm in atrial fibrillation: simplicity or complexity? Eur. Heart J. Suppl., September 1, 2007; 9(suppl_G): G17 - G25. [Abstract] [Full Text] [PDF]

				Y. Blaauw, U. Schotten, A. van Hunnik, H.R. Neuberger, and M.A. Allessie Cardioversion of persistent atrial fibrillation by a combination of atrial specific and non-specific class III drugs in the goat Cardiovasc Res, July 1, 2007; 75(1): 89 - 98. [Abstract] [Full Text] [PDF]

				I. C. Van Gelder and M. E.W. Hemels The progressive nature of atrial fibrillation: a rationale for early restoration and maintenance of sinus rhythm Europace, November 1, 2006; 8(11): 943 - 949. [Abstract] [Full Text] [PDF]

				P. M.R. Orth, J. C. Hesketh, C. K.H. Mak, Y. Yang, S. Lin, G. N. Beatch, A. M. Ezrin, and D. Fedida RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents Cardiovasc Res, June 1, 2006; 70(3): 486 - 496. [Abstract] [Full Text] [PDF]

				M. M. Scheinman and E. Keung The Year in Clinical Electrophysiology J. Am. Coll. Cardiol., March 21, 2006; 47(6): 1207 - 1213. [Full Text] [PDF]

				E. P. Gerstenfeld Does Rhythm Control Improve Functional Status in Patients With Atrial Fibrillation? J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1900 - 1901. [Full Text] [PDF]

				P. Zimetbaum An Argument for Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation Circulation, June 14, 2005; 111(23): 3150 - 3156. [Full Text] [PDF]