COR-ART: A multicenter, randomized, double-blind, placebo-controlled dose-ranging study to evaluate single oral doses of vanoxerine for conversion of recent-onset atrial fibrillation or flutter to normal sinus rhythm.

Abstract

BACKGROUND:

Restoration of sinus rhythm (SR) in patients with atrial fibrillation/atrial flutter (AF/AFL) is limited principally to direct current cardioversion. The multi-ion channel blocker vanoxerine may prove an effective alternative.

OBJECTIVE:

The purpose of this study was to assess vanoxerine, a 1,4-dialkylpiperazine derivative, for acute conversion of recent-onset, symptomatic AF and AFL.

METHODS:

One hundred four subjects with symptomatic AF/AFL for <7 days were randomized sequentially to single oral doses of vanoxerine 200, 300, and 400 mg or placebo. Holter monitors were examined for conversion to SR and proarrhythmia through ≥24 hours.

RESULTS:

Conversion to SR was dose related: 18.2%, 44.0%, and 52.0% within 4 hours, and 59.1%, 64.0%, and 84.0% within 24 hours, for the 200-, 300-, and 400-mg groups, respectively. This was significantly higher than placebo for the 300- and 400-mg groups within 4 hours (12.5% for placebo; P = .0138 and P = .0028, respectively) and for all doses within 24 hours (31.3% for placebo; P = .0421, P = .0138, P = .0001 for 200-, 300-, and 400-mg vanoxerine groups, respectively). Although vanoxerine caused significant dose-dependent QTcF (QT correction by Fridericia) prolongation, monomorphic or polymorphic ventricular tachycardia did not occur. Adverse events were mild and self-limited, with only the highest dose having a greater frequency than placebo.

CONCLUSION:

Oral vanoxerine converted AF/AFL to SR at a high rate, was well tolerated, and caused no ventricular proarrhythmia.

• Authors: Howard C Dittrich, Gregory K Feld, Tristram D Bahnson, A John Camm, Sergey Golitsyn, Amos Katz, Jason I Koontz, Peter R Kowey, Albert L Waldo, Arthur M Brown
• Journal: Heart rhythm (Heart Rhythm) Vol. 12 Issue 6 Pg. 1105-12 (Jun 2015) ISSN: 1556-3871 [Electronic] United States
• PMID: 25684233 (Publication Type: Controlled Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• Dopamine Uptake Inhibitors
• Piperazines
• vanoxerine

Topics

• Administration, Oral
• Aged
• Atrial Fibrillation (drug therapy)
• Atrial Flutter (drug therapy)
• Dopamine Uptake Inhibitors (administration & dosage)
• Double-Blind Method
• Electric Countershock
• Electrocardiography
• Electrocardiography, Ambulatory
• Female
• Humans
• Male
• Middle Aged
• Piperazines (administration & dosage)
• Prospective Studies