Effect of Dronedarone on Atrial Fibrosis Progression and Atrial Fibrillation Recurrence

Phase 4TerminatedNCT04704050

Tulane University School of Medicine22 enrolled

Overview

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.

The purpose of this trial is to determine whether dronedarone is effective in slowing the progression of fibrosis and decreasing atrial fibrillation recurrence in patients who have undergone ablation therapy. Patients with atrial fibrillation (AF) undergoing ablation will be stratified by age and gender (\>65 years and \<65 years, male and female) as well as by type of atrial fibrillation (paroxysmal, persistent, etc.) and then randomized to one of two trial groups. They will either receive dronedarone 400 mg BID (twice daily) (treatment group) or placebo (control group). The control group will be started on placebo, and treating physicians will be advised to limit the initiation of anti-arrhythmic drugs (standard of care, SOC) to necessary cases only, avoiding amiodarone and dronedarone. Each patient will receive a pre-ablation Cardiac Magnetic Resonance imaging (CMR) (SOC) scan, followed by scans at 3 and 12-month post-ablation. Quality of Life (QoL) changes will be evaluated from baseline and at 3 months and 12-months via the Atrial Fibrillation Effect on Quality-Of-Life (AFEQT) online questionnaire form. AF burden (frequency, duration and severity of an AF episode) if present, will be evaluated from baseline and at 3 months and 12-months via the Atrial Fibrillation Severity Scale (AFSS) online questionnaire form. Patients will be followed post-ablation for AF recurrence and burden assessment with a continuous 30-day ECG wearable patch starting at discharge (SOC), then at 3,6,9 and 12 months post-ablation Phone call visits will occur at 6 and 9 months to monitor for medication compliance as well as to assess that devices are working accordingly. Evaluation of adverse events (AE's) as well as whether a patient has reached any trial endpoints will be analyzed at this time. Physicians will be advised to avoid adjustments in drug therapy unless necessary (severely symptomatic patients, patients with heart failure). Severely symptomatic patients will be defined as, patients with non-tolerated palpitations or chest pain, dizziness, syncope, dyspnea, or suddenly reduced ability to exercise. Any initiation or change of an anti-arrhythmic treatment in the treatment or control group will be considered as a secondary endpoint. Patients will continue to be monitored for fibrosis progression and AF burden via CMR scans and ECG wearable devices until the end of the follow-up period. In the case of AF recurrence after ablation, anti-arrhythmic drugs (AAD) initiation or change will be left to the discretion of the treating physician.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

Conditions

Atrial Fibrillation Atrial Fibrillation Recurrent

Interventions

dronedarone 400 mg Oral TabletDRUG

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.

PlaceboDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Patients must meet the following criteria to be enrolled in the trial. * 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. Exclusion Criteria: Patients will be excluded from enrollment if any of the following criteria are present. * 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: 1. are pregnant or breast-feeding or plan to become pregnant during the study period or, 2. are not surgically sterile or, 3. are of childbearing potential and not practising two acceptable methods of birth control or, 4. 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.

Locations (4)

University of Colorado Health Memorial

Colorado Springs, Colorado, United States

Emory University

Atlanta, Georgia, United States

Tulane University School of Medicine

New Orleans, Louisiana, United States

Baylor College of Medicine

Houston, Texas, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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

Atrial Fibrillation Episodes

Atrial arrhythmia (AA) episodes associated with palpitations, chest pain, dyspnea, dizziness, syncope, or unusual fatigue and weakness were assessed using the Atrial Fibrillation Severity Scale (AFSS) questionnaire. The AFSS is a validated questionnaire designed to measure the burden of atrial arrhythmias, including atrial fibrillation and other irregular heart rhythms. The AA symptom burden score is derived from the AFSS summary score, which averages the frequency, duration, and patient-perceived severity of AA episodes. The AFSS symptom burden score ranges from 3 to 30, with higher scores indicating greater AA burden. Subscale scores (frequency, duration, and severity) are each rated on a scale of 1 to 10 and are averaged to calculate the total burden score. Patients completed the AFSS at baseline, 3 months, and 12 months. Reported data in the results table reflect the mean score at the 12-month time point.

Time frame: At baseline, at month 3, at month 12

Repeat Cardiac Ablation

Data from ClinicalTrials.gov

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