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A randomized trial of budiodarone in paroxysmal atrial fibrillation

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Objective

The aim of this study was to investigate the preliminary safety and efficacy of three doses of budiodarone in patients with paroxysmal atrial fibrillation.

Background

Budiodarone is a chemical analogue of amiodarone and shares its mixed ion channel electrophysiological properties. It has a shorter half-life than amiodarone.

Methods

Patients with paroxysmal atrial fibrillation and a previously implanted dual-chamber pacemaker capable of storing electrograms for at least 4 weeks were enrolled. Pacemaker memories were used to quantify atrial tachycardia/atrial fibrillation burden (AT/AFB). All antiarrhythmic drugs were stopped for greater than five half-lives and amiodarone greater than 3 months prior to enrollment. Following a 4-week baseline period to assess AT/AFB off antiarrhythmic drugs, patients with AT/AFB between 3% and 70% were blindly randomized to placebo, 200, 400, or 600 mg BID of budiodarone for 12 weeks followed by a 4-week washout period. Pacemakers were interrogated and safety assessed every 4 weeks. Pacemaker-derived electrograms were adjudicated blinded to treatment assignment. The primary study endpoint was percent change from baseline AT/AFB over 12 weeks of treatment compared to placebo.

Results

Of 72 randomized patients, 61 completed the study. The median reduction of AT/AFB for the 400 and 600 mg BID groups vs. placebo was 54% and 74% (p = 0.01 and 0.001), respectively. The budiodarone dose–response was statistically significant (p < 0.001). Number and duration of AT/AF episodes were reduced.

Conclusions

In this preliminary study, budiodarone at both higher doses significantly reduced AT/AFB. The study is novel because dual-chamber pacemakers, previously placed for standard clinical indications, were successfully used to monitor AT/AFB.

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Abbreviations

AT/AFB:

Atrial tachycardia/atrial fibrillation burden

AFSS:

Atrial Fibrillation Severity Scale

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Acknowledgments

Members of the Steering Committee are P. Dorian, M. Ezekowitz, A. Gillis, B. Thibault. Members of the Pacemaker Committee are A. Gillis, R. Yee, S. Saksena. M. Knowles is the independent statistician. Investigators who enrolled patients were: B. Coutu, Y.K. Chan, P. Costi, E. Crystal, P. Dorian, L. Sterns, A. Thang, D. Birnie, B. Thibault, M. Sturmer, S. Lepage, F. Ayala Paredes, J. Heath in Canada; A. Bauer, M. Borggrefe, S. Hohnloser, L. Lickfett, R. Ventura, J. Brachmann, A. Schuchert in Germany; Z. Kalarus, W. Kargul, K. Kawecka-Jaszcz, J. Kubica, A. Lubinski, P. Mitkowski, G. Opolski, G. Raczak, Z. Kornacewicz-Jach in Poland; M. Ezekowitz, T. Guarnieri, J. Ip, B. Strunk, A. Tran, A. Murphy, P. Underwood, S. Goel, S. Krueger, A. Cohen, D. Lustgarten, I. Khan, B. Pert, S. Mazer, P. Coffeen in the USA.

Funding sources

The study was funded by a grant from ARYx Therapeutics.

Disclosures

M. Ezekowitz received consulting fees and grant support from Boehringer Ingelheim, ARYx Therapeutics and Portola and consulting fees from Wyeth, Sanofi-Aventis, Bristol-Myers Squibb, Astra Zeneca, Daiichi Sankyo, and Medtronic. S. Hohnloser received consulting and lecture fees from Sanofi-Aventis, St. Jude Medical, Boehringer Ingelheim, and Procter & Gamble; consulting fees from Cardiome, ARYx Therapeutics and Bristol-Myers Squibb; research grants from Sanofi-Aventis and St. Jude Medical; and lecture fees from Boehringer Ingelheim. B. Thibault received consulting and lecture fees from St. Jude Medical, Sorin and Medtronic; research grants from St. Jude Medical and Sorin; and honoraria from ARYx Therapeutics. R. Nagarakanti and A. Lubinski have no disclosures. All other authors are employees of ARYx Therapeutics.

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Authors and Affiliations

  1. Lankenau Medical Center, Medical Science Building, 100 Lancaster Avenue, Suite 380, Wynnewood, PA, 19096, USA

    Michael D. Ezekowitz

  2. Vanderbilt University, Nashville, TN, USA

    Rangadham Nagarakanti

  3. Medical University Hospital, Lodz, Poland

    Andrzej Lubinski

  4. ARYx Therapeutics, Fremont, CA, USA

    Olga Bandman, Daniel Canafax, David J. Ellis, Peter G. Milner & Margaret Ziola

  5. Montreal Heart Institute, Montreal, QC, Canada

    Bernard Thibault

  6. J.W. Goethe University Hospital, Frankfurt, Germany

    Stefan H. Hohnloser

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  1. Michael D. Ezekowitz
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Correspondence to Michael D. Ezekowitz.

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Ezekowitz, M.D., Nagarakanti, R., Lubinski, A. et al. A randomized trial of budiodarone in paroxysmal atrial fibrillation. J Interv Card Electrophysiol 34, 1–9 (2012). https://doi.org/10.1007/s10840-011-9636-3

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  • DOI: https://doi.org/10.1007/s10840-011-9636-3

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