Effect of Addition of Dronedarone to Standard Rate Control Therapy on Ventricular Rate During Persistent Atrial Fibrillation (AFRODITE)

Study Overview
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Brief Summary
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The primary objective of this study is to: Assess whether the addition of dronedarone to existing conventional rate control therapy leads to a reduced ventricular rate after 1 week in patients with a high Heart Rate (HR) at rest during Atrial Fibrillation (AF) in comparison to an increase of conventional therapy. The secondary objectives of this study are to compare both study arms with regard to: Ventricular rate after 3 months Number of registered AF episodes Number of symptomatic AF episodes Severity of AF and AF-like symptoms Rate of premature study discontinuation Number of symptomatic episodes of bradycardia Incidence of low heart rate (<60 bpm)

Official Title
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The Effect of the Addition of Dronedarone to, Versus Increase of, Existing Conventional Rate Control Medication on Ventricular Rate During Persistent Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Dronedarone
* Drug: Beta blocker or calcium antagonist or digoxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persistent AF with HR >80 bpm at rest despite treatment with ≤ 2 rate control agents (i.e. beta blocker and/or calcium antagonist - Patients using digoxin are eligible) Documented AF in the past 24 hours Treated with the following rate control medication: beta blocker or calcium antagonist or beta blocker plus calcium antagonist or beta blocker plus digoxin or calcium antagonist plus digoxin Anticoagulant treatment in line with local guidelines Exclusion Criteria: Incapacitated patients Paroxysmal or permanent AF Use of class I or III anti-arrhythmic drugs in the past 12 weeks Scheduled cardioversion or pulmonary vein ablation Unstable New York Heart Association (NYHA) class III and all class IV Heart Failure AV block grade 2 or 3 Known severe renal impairment (serum creatinine > 180 μmol/l) Known severe hepatic impairment (AST, ALT > 3 x Upper Limit of Normal (ULN)) Contra-indication for dronedarone Participation in a clinical drug study in the 3 months prior to inclusion Women of childbearing potential, who do not use adequate contraception Lactating women The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 46 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Addition of dronedarone<br>Addition of Dronedarone to existing rate control medication (beta blocker and/or calcium antagonist) | Drug: Dronedarone<br>* Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg twice daily for 12 weeks (+/- 5 days)<br>* Other names: Multaq;|
| Active Comparator: Dose Increase<br>Dose increase of existing rate control medication (beta blocker or calcium antagonist or digoxin) | Drug: Beta blocker or calcium antagonist or digoxin<br>* Dose increase of beta blocker or calcium antagonist or digoxin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventricular rate |  | One week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventricular rate |  | 12 weeks | 
| Patients with registered AF episodes |  | Within the 12 weeks after randomization | 
| Patients with symptomatic AF episodes |  | Within the 12 weeks after randomization | 
| Severity of AF and AF-like symptoms |  | Within the 12 weeks after randomization | 
| Premature study discontinuation | Premature study discontinuation for all reasons including those where the patients must go off study prematurely as per protocol (ie. in case of cardioversion during the 1st study week, 2nd cardioversion after the 1st study week, addition of anti-arrhythmic drug, ablation or other surgical AF related intervention) | Within the 12 weeks after randomization | 
| Patients with symptomatic episodes of bradycardia |  | Within the 12 weeks after randomization | 
| Patients with low heart rate (<60 bpm) |  | Within the 12 weeks after randomization |