Atrial Fibrillation
Conditions
Brief summary
Primary Objective: \- Evaluate the rate of Atrial Fibrillation (AF) recurrences one month after randomization according to different timings of initiation of dronedarone. Secondary Objective: * Evaluate the rate of AF recurrences two months after randomization. * Assess the safety of the change from amiodarone to dronedarone * Assess dronedarone safety * Explore dronedarone and its active metabolite plasma level (in a subset of countries) * Explore potential Pharmacokinetic (PK) interaction between dronedarone and amiodarone (in a subset of countries)
Interventions
DRUGDRONEDARONE
Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Screening: * Persistent AF for more than 72 hours (documented by an ECG taken within the last 72 hours) for whom cardioversion, anti-arrhythmic treatment and anticoagulation treatment are indicated in the opinion of the Investigator * Naive of amiodarone treatment in the last three months * QTc Bazett \< 500 ms on 12-lead ECG, * At least one cardiovascular risk factor (i.e. age \> 70, hypertension, diabetes, prior cerebrovascular disease or left atrial diameter \>= 50 mm Randomization: * Outpatient and Inpatients (except patients hospitalized during screening period for SAE) * Sinus rhythm * Effective oral anticoagulation verified by International Normalized Ratio/INR (target \> 2) * QTc Bazett \< 500 ms and PR \< 280 ms on 12-lead ECG * Completed treatment period with amiodarone (28 days ± 2 days)
Exclusion criteria
Screening: * Contraindication to oral anticoagulation * Acute condition known to cause AF * Permanent AF * Paroxysmal AF * Bradycardia \< 50 bpm on the 12-lead ECG * Clinically overt congestive heart failure: * with New York Heart Association (NYHA) classes III and IV heart failure * with LVEF \< 35% * or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic * or unstable hemodynamic conditions * Severe hepatic impairment * Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol) if taken less than one week * Previous history of amiodarone intolerance or toxicity * Any contraindication as per dronedarone and amiodarone labelling * Wolff-Parkinson-White Syndrome * Previous ablation for atrial fibrillation or any planned ablation in the next 2 months * Contraindicated concomitant treatment: * Potent cytochrome P450 (CYP3A4) inhibitors * Use of drugs or herbal products that prolong the QT interval and known to increase the risk of Torsades de Pointes * Class I or III anti-arrhythmic drugs (including sotalol) Randomization: * Bradycardia \< 50 bpm on the 12-lead ECG * Clinically overt congestive heart failure: * with New York Heart Association (NYHA) classes III and IV heart failure * with LVEF \< 35% * or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic * or unstable hemodynamic conditions * Severe hepatic impairment * Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol) if taken less than one week * Patient in whom the following contraindicated concomitant treatment is mandatory: * Potent cytochrome P450 (CYP3A4) inhibitors * Use of drugs or herbal products that prolong the QT interval and known to increase the risk of Torsades de Pointes * Class I or III anti-arrhythmic drugs (including sotalol) The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AF recurrences | one month after randomization | two consecutives 12-lead ECG or Trans-Telephonic ECG monitoring (TTEM) approximatively 10 minutes apart and both showing AF |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AF recurrences | two months after randomization | — |
| Symptomatic bradycardia | two months after randomization | Heart rate at rest \< 50 beats per minute |
| Tachycardia | two months after randomization | Heart rate at rest \> 120 beats per minute |
| Dronedarone and amiodarone concentrations in plasma | 3 hours, 1 week, 2 weeks and 4 weeks after 1st Dronedarone intake | Limited to a subset of countries |
Countries
Australia, Austria, Estonia, Finland, France, Germany, Israel, Italy, Mexico, Netherlands, Portugal, South Korea, Spain, Switzerland, Taiwan, United Kingdom
Outcome results
None listed