New Formulations of Propafenone to Treat Atrial Fibrillation

Vanderbilt University

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Atrial Fibrillation

Treatments: Drug: (R)-propafenone; Drug: (S)-Propafenone; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02710669

151952

1R01HL124935-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 193 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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193 participants in 3 patient groups, including a placebo group

(R)-propafenone

Experimental group

Description:

Single intravenous dose of (R)-propafenone (2mg/kg) infused over 10 minutes

Treatment:

Drug: (R)-propafenone

(S)-Propafenone

Active Comparator group

Description:

Single intravenous dose of (S)-propafenone (2mg/kg) infused over 10 minutes

Treatment:

Drug: (S)-Propafenone

Placebo

Placebo Comparator group

Description:

Placebo (normal saline) is infused over 10 minutes

Treatment:

Drug: Placebo