A randomized trial of budiodarone in paroxysmal atrial fibrillation.
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.
Lankenau Medical Center, Medical Science Building, Wynnewood, PA 19096, USA. ezekowitzm@mlhs.org
Michael D
MD
Ezekowitz
Rangadham
R
Nagarakanti
Andrzej
A
Lubinski
Olga
O
Bandman
Daniel
D
Canafax
David J
DJ
Ellis
Peter G
PG
Milner
Margaret
M
Ziola
Bernard
B
Thibault
Stefan H
SH
Hohnloser
D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D016896:Treatment Outcome
D018927:Anti-Asthmatic Agents; C545283:budiodarone; D000638:Amiodarone