New Formulations of Propafenone to Treat Atrial Fibrillation

NCT02710669 | Terminated Phase 1 Results DMC

• 2 other identifiers: 1519521R01HL124935-01A1
• Study Type: interventional
• Target: 193
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrial Fibrillation

Keywords

ablation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Participants With Successful Inducibility of Atrial Fibrillation/Atrial Flutter Expressed as an Ordinal Variable Based on Stage of the Induction Protocol

  Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)

• Number of Participants With Successful Induction of 30 Seconds of Atrial Flutter

  Twenty minutes post-dosage to end of induction protocol (approximately 10 minutes)

Study Arms (3)

(R)-propafenone

EXPERIMENTAL

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

Drug: (R)-propafenone

(S)-Propafenone

ACTIVE COMPARATOR

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

Drug: (S)-Propafenone

Placebo

PLACEBO COMPARATOR

Placebo (normal saline) is infused over 10 minutes

Drug: Placebo

Interventions

(R)-propafenone DRUG

(R)-propafenone

(S)-Propafenone DRUG

(S)-Propafenone

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of atrial fibrillation
• Greater than or equal to 18 years of age
• Scheduled to undergo an atrial fibrillation ablation procedure
• Able to provide written informed consent

You may not qualify if:

• Long-standing persistent atrial fibrillation at the time of ablation (greater than 1 year of a continuous atrial fibrillation episode)
• Is in atrial fibrillation or atrial flutter the morning of the ablation procedure
• The presence of any of the following in a patient without a permanent pacemaker for implantable cardiac defibrillator
• sick sinus syndrome indicated by the inability to previously tolerate an antiarrhythmic drug due to bradycardia
• sinus bradycardia with a heart rate less than 50 beats per minute at the time of study drug administration
• right bundle branch block, left bundle branch block, or bifascicular block
• PR-interval \> 280ms, or history of 2nd or 3rd degree atrioventricular block
• Concomitant use of CYP3A4 and CYP2D6 inhibitors
• Previous surgical or catheter ablation for atrial fibrillation or Cox-Maze procedure
• Amiodarone use within 3 months prior to enrollment
• Antiarrhythmic drug (other than amiodarone) within 5 half-lives prior to atrial fibrillation ablation
• Expected life span \< 1 year
• Creatinine clearance \<30 mL/min
• Reversible cause of atrial fibrillation (ie. thyrotoxicosis)
• Unrevascularized coronary artery disease

Sponsors & Collaborators

• Vanderbilt University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

• 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.

  PMID: 24493699 BACKGROUND

• 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.

  PMID: 36166682 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Propafenone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals

Results Point of Contact

• Title: Benjamin Shoemaker, MD
• Organization: Vanderbilt University Medical Center

moore.b.shoemaker@vumc.org

615-322-2318

Study Officials

• Bjorn Knollmann, MD/PhD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

• Ben Shoemaker, MD

  Vanderbilt University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Study Record Dates

• First Submitted: March 12, 2016
• First Posted: March 17, 2016
• Study Start: October 1, 2016
• Primary Completion: March 11, 2020
• Study Completion: April 1, 2020
• Last Updated: June 3, 2022
• Results First Posted: May 14, 2021

Record last verified: 2022-06

Locations

US (1)