Effects of Dronedarone on Atrial Fibrillation Burden in Subjects With Permanent Pacemakers
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: Dronedarone; Placebo (for Dronedarone)
Intervention description: Film-coated tablet
Oral administration under fed conditions (during breakfast and dinner); Film-coated tablet strictly identical in appearance
Oral administration under fed conditions (during breakfast and dinner)
Intervention MeSH terms: Dronedarone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 112.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

Summary:

      Primary objective was to evaluate the effects of dronedarone on Atrial Fibrillation (AF)
      burden (i.e. percent time in AF) as measured on electrogram (EGM) in subjects with a
      permanent pacemaker.

      Secondary objectives were to evaluate:

        -  the effects of dronedarone on AF pattern characteristics i.e. ventricular rate during
           AF;

        -  the effects of dronedarone on subject-perceived AF burden and symptom severity as
           reported by subjects using the Atrial Fibrillation Severity Scale (AFSS);

        -  the incidence of electrical cardioversion (or overdrive pacing) during treatment;

        -  the safety of dronedarone.
    

Eligibility criteria:

        Inclusion criteria:

          -  Paroxysmal AF or atrial flutter (AFL) documented by evidence of AF/AFL and sinus
             rhythm within the prior 6 months;

          -  AF burden ≥1% on pacemaker EGM interrogation at screening, with at least one episode
             of AF within the previous 28 days;

          -  Programmable dual chamber pacemaker with lead placement no less than 3 months before
             screening, a minimum capability of storing 3 months or more of EGM data, and an
             expected remaining battery life of 1 year or more.

        Exclusion criteria:

          -  AF burden <1% on pacemaker EGM interrogation at screening;

          -  None of the following cardiovascular risk factors: Age ≥70 years, hypertension,
             diabetes mellitus, prior cardiovascular accident or systemic embolism, left atrium
             diameter ≥50 mm by M-mode or 2D echocardiography, or left ventricular ejection
             fraction ≤0.40 by M-mode or 2D echocardiography, cardiac catheterization, or nuclear
             cardiac imaging;

          -  Permanent AF;

          -  Evidence of persistent AF (continuous AF activity lasting longer than 7 days);

          -  Electrical cardioversion (or overdrive pacing) within 4 weeks prior to screening;

          -  Cardiac ablation procedure within 3 months prior to screening;

          -  Evidence of uncorrected atrial undersensing or oversensing documented in routine
             pacemaker evaluation at screening;

          -  Pacemaker programming requirements for the study not clinically feasible,
             contraindicated, or could have posed risk;

          -  Ongoing potentially dangerous symptoms when in AF/AFL such as angina pectoris,
             transient ischemic attacks, stroke, or syncope;

          -  New York Heart Association (NYHA) Class IV heart failure or NYHA Class II or III heart
             failure with a recent decompensation requiring hospitalization or referral to a
             specialized heart failure clinic within 4 weeks prior to screening;

          -  Evidence of clinical instability including hypotension, unstable angina and
             hemodynamically significant obstructive valvular disease, hemodynamically significant
             obstructive cardiomyopathy, a cardiac operation, or revascularization procedure within
             4 weeks prior to screening;

          -  Noncardiovascular illness or disorder that could have precluded participation or
             severely limit survival including cancer with metastasis and organ transplantation
             requiring immune suppression;

          -  Planned noncardiac or cardiac surgery or procedures including surgery for valvular
             heart disease, coronary artery bypass graft, percutaneous coronary intervention,
             cardiac transplantation or electrical cardioversion for AF/AFL;

          -  Need for concomitant medication that were prohibited in this trial: Antiarrhythmics,
             drugs or products that are strong inhibitors of CYP3A, CYP3A inducers;

          -  Chronic use of amiodarone within the 4 weeks prior to screening;

          -  Use of Class I or Class III antiarrhythmics (other than amiodarone) within 5-half
             lives prior to screening;

          -  Use of St John's wort, grapefruit juice, or drugs that prolong the QT interval and
             might have increased the risk of torsade de pointes;

          -  Inability or unwillingness to comply with oral anticoagulation therapy, if indicated;

          -  Bazett corrected QT interval interval ≥500 msec at screening (if in sinus rhythm);

          -  Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood
             pressure ≥ 100mmHg) at screening;

          -  Uncorrected hypokalemia (serum potassium <3.5 mEq/L)

          -  Severe hepatic impairment (ie, Child-Pugh Class C), abnormal liver function test
             defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or
             bilirubin >2 X upper limit of normal (ULN), or renal impairment defined as serum
             creatinine >2.0 mg/dL at screening;

          -  Uncontrolled diabetes mellitus (documented history of HbA1c >10% at the most recent
             assessment prior to screening);

          -  Pregnant woman or woman of childbearing potential not on adequate birth control;

          -  Breastfeeding woman;

          -  Previous (within 2 months prior to screening) or current participation in another
             clinical trial with an investigational drug (under development) or investigational
             device.

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.