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:
|
|
|
|
 
A. Arya, J. Silberbauer, S. L. Teichman, P. Milner, N. Sulke, and A. J. Camm
A preliminary assessment of the effects of ATI-2042 in subjects with paroxysmal atrial fibrillation using implanted pacemaker methodology
Europace,
April 1, 2009;
11(4):
458 - 464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. F. McBride
The Emerging Role of Antiarrhythmic Compounds With Atrial Selectivity in the Management of Atrial Fibrillation
J. Clin. Pharmacol.,
March 1, 2009;
49(3):
258 - 267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. L. Mao, J. J. Wheeler, L. Clohs, G. N. Beatch, and J. Keirns
Pharmacokinetics of Novel Atrial-Selective Antiarrhythmic Agent Vernakalant Hydrochloride Injection (RSD1235): Influence of CYP2D6 Expression and Other Factors
J. Clin. Pharmacol.,
January 1, 2009;
49(1):
17 - 29.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Comtois, M. Sakabe, E. J. Vigmond, M. Munoz, A. Texier, A. Shiroshita-Takeshita, and S. Nattel
Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers: insights from mathematical models and experimental correlates
Am J Physiol Heart Circ Physiol,
October 1, 2008;
295(4):
H1489 - H1504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
