Clinical trial NCT02710669: New Formulations of Propafenone to Treat Atrial Fibrillation
Official title: Comparison of (R) and (S) Propafenone for Prevention of Atrial Fibrillation Induction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Atrial Fibrillation
Keywords: ablation
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-03-17
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Propafenone is a currently used medicine to treat atrial fibrillation and is a mixture of two compounds, (R)-propafenone and (S)-propafenone. In this study, the investigators will randomize participants to (R)-propafenone, (S)-propafenone, or placebo.

Detailed description: Atrial fibrillation is a common cardiac arrhythmia that needs development of more effective medications. Propafenone is a medicine currently used to treat atrial fibrillation and is a mixture of two compounds, (R)-propafenone and (S)-propafenone. The investigators have discovered that purified (R)-propafenone may be more effective than (S)-propafenone for treatment of atrial fibrillation, and that (S)-propafenone reduces the efficacy of (R)-propafenone when administered as a mixture. This study will compare the ability of (R)-propafenone, (S)-propafenone, and placebo to suppress the induction of atrial fibrillation in participants undergoing an atrial fibrillation ablation procedure.

Eligibility criteria: Inclusion:

1. History of atrial fibrillation
2. Greater than or equal to 18 years of age
3. Scheduled to undergo an atrial fibrillation ablation procedure
4. Able to provide written informed consent

Exclusion:

1. Long-standing persistent atrial fibrillation at the time of ablation (greater than 1 year of a continuous atrial fibrillation episode)
2. Is in atrial fibrillation or atrial flutter the morning of the ablation procedure
3. The presence of any of the following in a patient without a permanent pacemaker for implantable cardiac defibrillator

   1. sick sinus syndrome indicated by the inability to previously tolerate an antiarrhythmic drug due to bradycardia
   2. sinus bradycardia with a heart rate less than 50 beats per minute at the time of study drug administration
   3. right bundle branch block, left bundle branch block, or bifascicular block
   4. PR-interval \> 280ms, or history of 2nd or 3rd degree atrioventricular block
4. Concomitant use of CYP3A4 and CYP2D6 inhibitors
5. Previous surgical or catheter ablation for atrial fibrillation or Cox-Maze procedure
6. Amiodarone use within 3 months prior to enrollment
7. Antiarrhythmic drug (other than amiodarone) within 5 half-lives prior to atrial fibrillation ablation
8. Expected life span \< 1 year
9. Creatinine clearance \<30 mL/min
10. Reversible cause of atrial fibrillation (ie. thyrotoxicosis)
11. Unrevascularized coronary artery disease
12. Canadian class IV angina
13. Left ventricular ejection fraction \<40%
14. New York Heart Association Class III or IV symptoms
15. Previous heart transplantation
16. Planned heart transplantation or ventricular assist device
17. Cardiac/thoracic surgery \<6 months prior to enrollment
18. Severe asthma or chronic obstructive pulmonary disease
19. Breastfeeding

Primary outcomes:
measure: Number of Participants With Successful Induction of 30 Seconds of Atrial Fibrillation/Atrial Flutter
timeFrame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
Secondary outcomes:
measure: Number of Participants With Successful Inducibility of Atrial Fibrillation/Atrial Flutter Expressed as an Ordinal Variable Based on Stage of the Induction Protocol
timeFrame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
measure: Number of Participants With Successful Induction of 30 Seconds of Atrial Flutter
timeFrame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Bjorn Knollmann, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University
name: Ben Shoemaker, MD
role: STUDY_DIRECTOR
References:
citation: Faggioni M, Savio-Galimberti E, Venkataraman R, Hwang HS, Kannankeril PJ, Darbar D, Knollmann BC. Suppression of spontaneous ca elevations prevents atrial fibrillation in calsequestrin 2-null hearts. Circ Arrhythm Electrophysiol. 2014 Apr;7(2):313-20. doi: 10.1161/CIRCEP.113.000994. Epub 2014 Feb 3.
citation: Shoemaker MB, Yoneda ZT, Crawford DM, Akers WS, Richardson T, Montgomery JA, Phillips S, Shyr Y, Saavedra P, Estrada JC, Kanagasundram A, Shen ST, Michaud GF, Crossley G, Ellis CR, Knollmann BC. A Mechanistic Clinical Trial Using (R)- Versus (S)-Propafenone to Test RyR2 (Ryanodine Receptor) Inhibition for the Prevention of Atrial Fibrillation Induction. Circ Arrhythm Electrophysiol. 2022 Oct;15(10):e010713. doi: 10.1161/CIRCEP.121.010713. Epub 2022 Sep 27.