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New Formulations of Propafenone to Treat Atrial Fibrillation

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ClinicalTrials.gov Identifier: NCT02710669
Recruitment Status : Terminated (Study halted/terminated prematurely due to COVID.)
First Posted : March 17, 2016
Results First Posted : May 14, 2021
Last Update Posted : June 9, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Bjorn Knollmann, Vanderbilt University

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.

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: (R)-propafenone Drug: (S)-Propafenone Drug: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 193 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of (R) and (S) Propafenone for Prevention of Atrial Fibrillation Induction
Study Start Date : October 2016
Actual Primary Completion Date : March 11, 2020
Actual Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


  2. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02710669


Locations
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United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Bjorn Knollmann, MD/PhD Vanderbilt University
Study Director: Ben Shoemaker, MD Vanderbilt University
  Study Documents (Full-Text)

Documents provided by Bjorn Knollmann, Vanderbilt University:
Informed Consent Form  [PDF] October 23, 2019

Publications:
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Responsible Party: Bjorn Knollmann, Professor of Medicine and Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT02710669    
Other Study ID Numbers: 151952
1R01HL124935-01A1 ( U.S. NIH Grant/Contract )
First Posted: March 17, 2016    Key Record Dates
Results First Posted: May 14, 2021
Last Update Posted: June 9, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Bjorn Knollmann, Vanderbilt University:
ablation
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Propafenone
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action