New Formulations of Propafenone to Treat Atrial Fibrillation

Atrial Fibrillation Clinical Trial

Official title:

Comparison of (R) and (S) Propafenone for Prevention of Atrial Fibrillation Induction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02710669
• Other study ID #: 151952
• Secondary ID: 1R01HL124935-01A
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 2016
• Est. completion date: April 2020

Study information

• Verified date: June 2022
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 193
• Est. completion date: April 2020
• Est. primary completion date: March 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• (R)-propafenone

• (S)-Propafenone

• Placebo

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Successful Induction of 30 Seconds of Atrial Fibrillation/Atrial Flutter	A rapid atrial pacing protocol was used to attempt to induce atrial fibrillation/atrial flutter. Twenty minutes after start of the study drug, participants underwent placement of a decapolar coronary sinus catheter. Pacing was performed from the proximal electrode at 20 milliamps and a pulse width of 2 ms. Bursts from the CS proximal electrode were induced to attempt atrial fibrillation.	Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
Secondary	Number of Participants With Successful Inducibility of Atrial Fibrillation/Atrial Flutter Expressed as an Ordinal Variable Based on Stage of the Induction Protocol	Inducibility of atrial fibrillation (AF) or atrial flutter (AFL) expressed as an ordinal variable based on stage of the induction protocol.; Stage 1 measured the AV block (Wenckebach) cycle length (AVBCL), AV node effective refractory period (AVN ERP) and atrial ERP (AERP). AVN ERP and AERP were measured at drive trains (S1) of 600 ms and 450 ms. Extrastimuli (S2) were introduced starting at a coupling interval of 500ms and decremented by 10ms with each pacing train.; Stage 2 consisted of 15-beat bursts from the CS proximal electrode. The starting cycle length was 250ms, which was decremented by 10ms with each burst. A 10-second rest period was used between bursts. Step 2 was complete when 1:1 atrial capture was lost or a minimum cycle length of 180ms was reached.; Stage 3 consisted of 15-second bursts. The cycle length used for the bursts was the fastest cycle length achieved during Step 2 that maintained 1:1 atrial conduction.	Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
Secondary	Number of Participants With Successful Induction of 30 Seconds of Atrial Flutter	A rapid atrial pacing protocol was used to attempt to induce atrial flutter. Twenty minutes after start of the study drug, participants underwent placement of a decapolar coronary sinus catheter. Pacing was performed from the proximal electrode at 20 milliamps and a pulse width of 2 ms. Bursts from the CS proximal electrode were induced to attempt atrial flutter.	Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)