Effect of Dronedarone on Atrial Fibrosis Progression and Atrial Fibrillation Recurrence

NCT04704050 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 2830294
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

Patients who have undergone cardiac ablation will be randomized and blinded to one of two groups; one group will receive dronedarone while the other group will receive a placebo. The incidence of atrial fibrillation recurrence, as well as atrial fibrosis progression, will be analyzed between the two trial groups.

Conditions

Atrial Fibrillation; Atrial Fibrillation Recurrent

Keywords

Atrial Fibrillation; Atrial Fibrillation Recurrent; Heart Murmur; Dronedarone; Atrial Fibrosis; Atrial Fibrosis Progression; Atrial Fibrosis Regression; Atrial Arrhythmia; Cardiac Arrhythmia; Cardiovascular Events; Multaq

Outcome Measures

Primary Outcomes (2)

• Post-ablation Atrial Fibrillation Recurrence

  Investigators monitored subjects upon discharge, 24-48 hours after AF ablation. This was recorded by either the occurrence of a single positive atrial arrhythmias (AA) ECG reading on a 12-lead ECG, Holter monitor, obtained on the daily event strips from the Preventice monitoring device, or 30-day monitoring patch.

  Up to 56 weeks. From date of ablation until the date of first documented Atrial Fibrillation recurrence, whichever came first, assessed up to 56 weeks.

• Post-ablation Atrial Fibrillation Recurrence Documented by an AAD Initiation

  New anti-arrhythmic drug (AAD) initiation for AF recurrence after AF ablation, including initiation of the treatment during the blanking period, or with no available positive ECG reading.

  Up to 56 weeks. From date of ablation until the date of first documented Atrial Fibrillation recurrence, whichever came first, assessed up to 56 weeks.

Secondary Outcomes (6)

• Atrial Fibrillation Episodes

  At baseline, at month 3, at month 12

• Repeat Cardiac Ablation

  1 year

• Cardioversion

  1 year

• Atrial Fibrillation Burden

  1 year

• Quality of Life (Online Questionnaire Form)

  At baseline, at month 3, at month 12

Other Outcomes (3)

• Hospitalization

  1 year

• Mortality

  1 year

• Stroke/ Transient Ischemic Attacks (TIA)

  1 year

Study Arms (2)

Treatment Group

ACTIVE COMPARATOR

Dronedarone 400 mg orally, twice per day (BID)

Drug: dronedarone 400 mg Oral Tablet

Control Group

PLACEBO COMPARATOR

Placebo tablet orally, twice per day (BID)

Drug: Placebo

Interventions

dronedarone 400 mg Oral Tablet DRUG

Dronedarone is an anti-arrhythmic drug with properties belonging to Vaughan-Williams class I-IV. Participants will receive dronedarone 400 mg tablet, to be taken orally and twice daily for 52 weeks.

Also known as: Multaq®

Treatment Group

Placebo DRUG

Participants will receive a placebo tablet matching the physical appearance of dronedarone, to be taken orally and twice daily for 52 weeks.

Control Group

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participant eligibility is based on the self-representation of gender identity.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged over 18 years of age.
• Patients with paroxysmal or persistent atrial fibrillation who are undergoing ablation of atrial fibrillation, regardless of whether they were receiving an anti-arrhythmic drug (AADs) before enrollment or not.

You may not qualify if:

• Any health-related gadolinium/MRI contraindications (e.g. allergy to gadolinium, pacemakers, Implantable Cardioverter Defibrillators \[ICD's\], other devices/implants contraindicated for use of MRI, etc.).
• Patients weighing \>300 Ibs. (MRI quality decreases as BMI increases).
• Patients with contraindications to dronedarone. (Including patients with decompensated heart failure or class NYHA IV (New York Heart Association Class IV), second or third-degree atrioventricular (AV) block or sick-sinus syndrome \[except when used in conjunction with a functioning pacemaker\]), concomitant use of strong cytochrome P450, family 3, subfamily A (CYP-3A) inhibitors or other Class I or III AADs, drug or herbal products that prolongs the QT interval and may induce Torsades de Pointes.
• Liver or lung toxicity related to the previous use of amiodarone, severe hepatic impairment including any stage of cirrhosis and acute liver failure, bradycardia \<50bpm, QTc Bazett interval \>500ms or PR interval \>280ms, or hypersensitivity to the active substance or to any of its excipients.
• Acute or chronic severe renal disease with a low glomerular filtration rate (GFR), \<30 mL per minute per 1.73m2 will be excluded from the trial.
• Patients with a history of prior left atrial ablation or valvular cardiac surgery (myocardial scarring/fibrosis from prior surgeries may confound data).
• Pre-menopausal (last menstruation \<1 year prior to screening) who:
• are pregnant or breast-feeding or plan to become pregnant during the study period or,
• are not surgically sterile or,
• are of childbearing potential and not practising two acceptable methods of birth control or,
• do not plan to continue practising two acceptable methods of birth control throughout the trial (highly effective methods of birth control are defined as those, used alone, or in combination, that result in a low failure rate i.e. less than 1% per year when used consistently and correctly).
• Patients who do not have access to the Internet/e-mail.
• Patients without daily access to a smart phone-compatible with ECG Check device application and ability to upload ECG tracings for the entire follow-up period.
• Patients unable or unwilling to return to the clinic for follow up CMR scans.
• Patients with cognitive impairments who are unable to give informed consent.

Sponsors & Collaborators

• Tulane University School of Medicine: lead
• University of Washington: collaborator
• Marrek, INC: collaborator
• Sanofi: collaborator
• Preventice: collaborator
• Mckesson: collaborator

Study Sites (4)

University of Colorado Health Memorial

Colorado Springs, Colorado, 80909, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (9)

• Hagens VE, Ranchor AV, Van Sonderen E, Bosker HA, Kamp O, Tijssen JG, Kingma JH, Crijns HJ, Van Gelder IC; RACE Study Group. Effect of rate or rhythm control on quality of life in persistent atrial fibrillation. Results from the Rate Control Versus Electrical Cardioversion (RACE) Study. J Am Coll Cardiol. 2004 Jan 21;43(2):241-7. doi: 10.1016/j.jacc.2003.08.037.

  PMID: 14736444 BACKGROUND

• Blomstrom-Lundqvist C, Gizurarson S, Schwieler J, Jensen SM, Bergfeldt L, Kenneback G, Rubulis A, Malmborg H, Raatikainen P, Lonnerholm S, Hoglund N, Mortsell D. Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation: The CAPTAF Randomized Clinical Trial. JAMA. 2019 Mar 19;321(11):1059-1068. doi: 10.1001/jama.2019.0335.

  PMID: 30874754 BACKGROUND

• Marrouche NF, Brachmann J, Andresen D, Siebels J, Boersma L, Jordaens L, Merkely B, Pokushalov E, Sanders P, Proff J, Schunkert H, Christ H, Vogt J, Bansch D; CASTLE-AF Investigators. Catheter Ablation for Atrial Fibrillation with Heart Failure. N Engl J Med. 2018 Feb 1;378(5):417-427. doi: 10.1056/NEJMoa1707855.

  PMID: 29385358 BACKGROUND

• Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, Noseworthy PA, Rosenberg YD, Jeffries N, Mitchell LB, Flaker GC, Pokushalov E, Romanov A, Bunch TJ, Noelker G, Ardashev A, Revishvili A, Wilber DJ, Cappato R, Kuck KH, Hindricks G, Davies DW, Kowey PR, Naccarelli GV, Reiffel JA, Piccini JP, Silverstein AP, Al-Khalidi HR, Lee KL; CABANA Investigators. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019 Apr 2;321(13):1261-1274. doi: 10.1001/jama.2019.0693.

  PMID: 30874766 BACKGROUND

• Marrouche NF, Wilber D, Hindricks G, Jais P, Akoum N, Marchlinski F, Kholmovski E, Burgon N, Hu N, Mont L, Deneke T, Duytschaever M, Neumann T, Mansour M, Mahnkopf C, Herweg B, Daoud E, Wissner E, Bansmann P, Brachmann J. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. JAMA. 2014 Feb 5;311(5):498-506. doi: 10.1001/jama.2014.3.

  PMID: 24496537 BACKGROUND

• Kheirkhahan M, Baher A, Goldooz M, Kholmovski EG, Morris AK, Csecs I, Chelu MG, Wilson BD, Marrouche NF. Left atrial fibrosis progression detected by LGE-MRI after ablation of atrial fibrillation. Pacing Clin Electrophysiol. 2020 Apr;43(4):402-411. doi: 10.1111/pace.13866.

  PMID: 31867751 BACKGROUND

• Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen C, Connolly SJ; ATHENA Investigators. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009 Feb 12;360(7):668-78. doi: 10.1056/NEJMoa0803778.

  PMID: 19213680 BACKGROUND

• Akoum N, Fernandez G, Wilson B, Mcgann C, Kholmovski E, Marrouche N. Association of atrial fibrosis quantified using LGE-MRI with atrial appendage thrombus and spontaneous contrast on transesophageal echocardiography in patients with atrial fibrillation. J Cardiovasc Electrophysiol. 2013 Oct;24(10):1104-9. doi: 10.1111/jce.12199. Epub 2013 Jul 11.

  PMID: 23844972 BACKGROUND

• Marrouche NF, Dagher L, Wazni O, Akoum N, Mansour M, El Hajjar AH, Bhatnagar A, Hua H; EDORA Investigators. Effect of DrOnedarone on atrial fibrosis progression and atrial fibrillation recurrence postablation: Design of the EDORA randomized clinical trial. J Cardiovasc Electrophysiol. 2021 Dec;32(12):3203-3210. doi: 10.1111/jce.15274. Epub 2021 Nov 2.

  PMID: 34664772 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Heart Murmurs; Arrhythmias, Cardiac

Interventions

Dronedarone; Tablets

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amiodarone; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

Early termination and incomplete data collections for several outcome measures. All data that was collected was added to the results section for this study.

Results Point of Contact

• Title: Nassir Marrouche
• Organization: Tulane University

nmarrouche@tulane.edu

504-988-2025

Study Officials

• Nassir F Marrouche, MD

  Tulane University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 11, 2021
• Study Start: May 15, 2021
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: October 30, 2025
• Results First Posted: October 16, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)