A Randomized, international, multi-center, open-label study to document pharmacokinetics and optimal timing of initiation of dronedarone TreatmEnt following long-term aMIodarone in patients with paroxysmal or perSistent Atrial Fibrillation whatever the reason for the change of treatment - ARTEMIS AF Long-Term
- Conditions
- Paroxysmal or persistent atrial fibrillationMedDRA version: 12.1Level: PTClassification code 10003658Term: Atrial fibrillation
- Registration Number
- EUCTR2010-019247-19-GR
- Lead Sponsor
- sanofi aventis groupe
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 165
Inclusion criteria at screening:
I01. Male or female adults aged 18 years or more,
I02. Outpatients,
I03. Patients with 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,
I04. Requiring a change from amiodarone treatment whatever the reason, but without major amiodarone-related toxicity (interstitial lung disease, thyroid or hepatotoxicity),
I05. Patients with at least one cardiovascular risk factor (i.e. age > 70, hypertension, diabetes, prior cerebrovascular disease, left atrial diameter = 50 mm or left ventricular ejection fraction [LVEF] < 40%),
I06. Patients receiving effective anticoagulation according to ACC/AHA/ESC guidelines,
I07. QTcB < 500 ms on 12-lead ECG,
I08. Signed written informed consent.
Inclusion Criteria: to be checked before randomization
I09. Patients in sinus rhythm (Note: if cardioversion is performed on Day 1 prior to randomization, then the patient must be in sinus rhythm for at least an hour before randomization),
I10. Patients under effective oral anticoagulation according to ACC/AHA/ESC 2006 guidelines, verified by INR (target > 2),
I11. QTcB < 500 ms and PR < 280 ms on 12-lead ECG,
I12. Outpatients (only hospitalization of 48h for a planned cardioversion will be allowed). Patients currently hospitalized for Serious Adverse Event (SAE) are not eligible for randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Exclusion criteria at screening:
E01. Contraindication to oral anticoagulation,
E02. Documented AF episode motivating inclusion in the study after an acute condition known to cause AF (e.g. alcohol intake, thyrotoxicosis, acute infection, pericarditis, pulmonary embolism, cardiac surgery),
E03. Patients with permanent AF in which cardioversion has failed,
E04. Bradycardia < 50 beats per minute (bpm) at rest on the 12-lead ECG,
E05. Clinically overt congestive heart failure:
owith New York Heart Association (NYHA) class III and IV heart failure,
oor NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic,
oor any patients in unstable hemodynamic conditions.
E06. Women of childbearing potential without adequate birth control (e.g. oral contraception or intra-uterine device [IUD]) or not menopaused, not sterile or not hysterectomized,
E07. Pregnant women,
E08. Breastfeeding women,
E09. Previous (2 preceding months) or current participation in another clinical trial with an investigational drug or with an investigational device,
E10. Clinically relevant hematologic, underlying hepatobiliary disease, gastrointestinal, pulmonary, endocrinologic, psychiatric, neurological or dermatological disease,
E11. Severe hepatic impairment,
E12. Severe renal impairment (creatinine clearance < 30 mL/min),
E13. Serum potassium <3.5 millimol/liter (mmol/l) (in patients with hypokalemia, potassium deficiency must be corrected before randomization) or > 5.5 mmol/l,
E14. Magnesemia < 0.8 mml/l (in patient with hypo-magnesemia, magnesium deficiency must be corrected before randomization),
E15. Unstable angina pectoris (ischemic symptoms during the last 7 days) or recent myocardial infarction (MI) (< 6 weeks),
E16. First degree family history of sudden cardiac death below age 50 years in the absence of coronary heart disease,
E17. Second- or third- degree Atrio-Ventricular block or sick sinus syndrome (except when used in conjunction with a functioning pacemaker),
E18. Ongoing potentially severe symptoms when in AF such as angina pectoris, transient ischemic attacks, stroke, syncope, as judged by the investigator,
E19. Wolff-Parkinson-White Syndrome,
E20. Previous catheter ablation for atrial fibrillation,
E21. Catheter ablation scheduled in the next 10 weeks,
E22. Previous history of amiodarone intolerance or toxicity,
E23. History of thyroid dysfunction,
E24. Hypersensitivity to dronedarone or any of the excipients,
E25. Patients previously treated 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),
E26. Patients in whom a contraindicated concomitant treatment is mandatory
Exclusion criteria to be checked before randomization
E27. Bradycardia < 50 bpm on the 12-lead ECG before randomization,
E28. Clinically overt congestive heart failure:
owith New York Heart Association (NYHA) class III and IV heart failure,
oor NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic,
oas well any patients in unstable hemodynamic conditions.
E29. Serum potassium <3.5 millimol/liter (mmol/l) (in patients with hypokalemia, potassium deficiency must be corrected before randomization) or > 5.5 mmol/l,
E30. Magnesemi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to explore dronedarone and SR35021 (active metabolite) PK profiles according to different timings of dronedarone initiation.;Secondary Objective: The secondary efficacy objectives are:<br> <br>•To explore potential PK interaction between dronedarone and amiodarone,<br>•To evaluate the rate of AF recurrence one month and two months after randomization,<br>•To assess the safety of the change from amiodarone to dronedarone and dronedarone safety;Primary end point(s): Plasma levels of dronedarone and its metabolite SR35021 (AUC0-12hours and Cmax).<br>•at randomization (baseline),<br>•3 hours after the first dose of dronedarone,<br>•after one week of treatment with dronedarone (before dronedarone dose),<br>•after two weeks of treatment with dronedarone (before dronedarone dose),<br>•after four weeks of treatment with dronedarone (before dronedarone dose).<br>
- Secondary Outcome Measures
Name Time Method