Pharmacokinetics and Optimal Timing of Dronedarone Initiation Following Long-term Amiodarone in Patients With Paroxysmal or Persistent Atrial Fibrillation (ARTEMIS AF LT)
Atrial Fibrillation
About this trial
This is an interventional treatment trial for Atrial Fibrillation
Eligibility Criteria
Inclusion criteria:
Screening:
- Paroxysmal or persistent AF having received at least 6 months of amiodarone before screening with at least the last 2 months at a regimen of 200 mg/day (during at least 5 days per week) prior to screening
- Requiring a change from amiodarone treatment whatever the reason, but without liver, lung or thyroid toxicity related to previous use of amiodarone
- At least one cardiovascular risk factor (i.e. age > 70, hypertension, diabetes, prior cerebrovascular disease or left atrial diameter >= 50 mm
- Effective anticoagulation treatments verified by International Normalized Ratio (INR) (target INR > 2)
- QTc Bazett < 500 ms on 12-lead ECG
Randomization:
- Outpatients and Inpatients (except patients hospitalized during screening period for SAE)
- Sinus rhythm
- Effective oral anticoagulation treatment verified by INR (target INR > 2). INR should be closely monitored after initiating dronedarone in patients taking vitamin K antagonist as per their label
- QTc Bazett < 500 ms and PR < 280 ms on 12-lead ECG
Exclusion criteria:
Screening:
- Contraindication to oral anticoagulation
- Acute condition known to cause AF
- Permanent AF
- Bradycardia < 50 bpm at rest on the 12-lead ECG
- History of, or current heart failure or left ventricular systolic dysfunction
- Unstable hemodynamic conditions
- Severe hepatic impairment
- Wolff-Parkinson-White Syndrome
- Previous catheter ablation for atrial fibrillation or catheter ablation scheduled in the next 10 weeks
- Previous history of Amiodarone intolerance or toxicity
- History of thyroid dysfunction
Mandatory contraindicated concomitant treatment:
- potent cytochrome P450 (CYP3A4) inhibitors
- drugs or herbal products that prolong the QT interval and known to increase the risk of Torsade de Pointes
- Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol) other than amiodarone if the anti-arrhythmic drug was taken less than one week before the day of screening (if taken more than one week before screening, the patient can be included)
Randomization
- Bradycardia < 50 bpm on the 12-lead ECG
- History of, or current heart failure or left ventricular systolic dysfunction
- Unstable hemodynamic conditions
- Severe hepatic impairment
Mandatory contraindicated concomitant treatment:
- potent cytochrome P450 (CYP3A4) inhibitors
- drugs or herbal products that prolong the QT interval and known to increase the risk of Torsade de Pointes
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number 170001
- Investigational Site Number 170002
- Investigational Site Number 170003
- Investigational Site Number 170006
- Investigational Site Number 170007
- Investigational Site Number 170005
- Investigational Site Number 203005
- Investigational Site Number 203003
- Investigational Site Number 203002
- Investigational Site Number 203007
- Investigational Site Number 203001
- Investigational Site Number 203004
- Investigational Site Number 203008
- Investigational Site Number 203006
- Investigational Site Number 208-001
- Investigational Site Number 208-002
- Investigational Site Number 208-003
- Investigational Site Number 250-004
- Investigational Site Number 250-005
- Investigational Site Number 250-003
- Investigational Site Number 250-002
- Investigational Site Number 250-001
- Investigational Site Number 250-006
- Investigational Site Number 276-001
- Investigational Site Number 276-002
- Investigational Site Number 276-005
- Investigational Site Number 276-003
- Investigational Site Number 276-004
- Investigational Site Number 484003
- Investigational Site Number 484002
- Investigational Site Number 484001
- Investigational Site Number 484005
- Investigational Site Number 484004
- Investigational Site Number 484006
- Investigational Site Number 724004
- Investigational Site Number 724001
- Investigational Site Number 724005
- Investigational Site Number 724002
- Investigational Site Number 724003
- Investigational Site Number 724006
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Group A
Group B
Group C
Dronedarone 400 mg twice daily for 8 weeks starting from randomization. The last 2 months regimen of Amiodarone 200 mg/day is continued until randomization.
Dronedarone 400 mg twice daily for 6 weeks starting 2 weeks after randomization. The last 2 months regimen of Amiodarone 200 mg/day is continued until randomization.
Dronedarone 400 mg twice daily for 4 weeks starting 4 weeks after randomization. The last 2 months regimen of Amiodarone 200 mg/day is continued until randomization.