New Formulations of Propafenone to Treat Atrial Fibrillation

June 1, 2022 updated by: Bjorn Knollmann, Vanderbilt University

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

193

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: (R)-propafenone
Single intravenous dose of (R)-propafenone (2mg/kg) infused over 10 minutes
Drug: (R)-propafenone
Active Comparator: (S)-Propafenone
Single intravenous dose of (S)-propafenone (2mg/kg) infused over 10 minutes
Drug: (S)-Propafenone
Placebo Comparator: Placebo
Placebo (normal saline) is infused over 10 minutes
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Successful Induction of 30 Seconds of Atrial Fibrillation/Atrial Flutter
Time Frame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Successful Inducibility of Atrial Fibrillation/Atrial Flutter Expressed as an Ordinal Variable Based on Stage of the Induction Protocol
Time Frame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)

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)
Number of Participants With Successful Induction of 30 Seconds of Atrial Flutter
Time Frame: Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Bjorn Knollmann, MD/PhD, Vanderbilt University
  • Study Director: Ben Shoemaker, MD, Vanderbilt University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2016

Primary Completion (Actual)

March 11, 2020

Study Completion (Actual)

April 1, 2020

Study Registration Dates

First Submitted

March 12, 2016

First Submitted That Met QC Criteria

March 16, 2016

First Posted (Estimate)

March 17, 2016

Study Record Updates

Last Update Posted (Actual)

June 3, 2022

Last Update Submitted That Met QC Criteria

June 1, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 151952
  • 1R01HL124935-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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