A Randomized, international, multi-center, open-label study to document optimal timing of initiation of dronedarone TreatmEnt after conversion with loading dose of aMIodarone in patients with perSistent Atrial Fibrillation requiring conversion of AF - ARTEMIS AF Loading

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-016818-24-AT
• Date of registration: 18/05/2010
• Prospective Registration: Yes
• Primary sponsor: sanofi aventis
• Public title: A Randomized, international, multi-center, open-label study to document optimal timing of initiation of dronedarone TreatmEnt after conversion with loading dose of aMIodarone in patients with perSistent Atrial Fibrillation requiring conversion of AF - ARTEMIS AF Loading
• Scientific title: A Randomized, international, multi-center, open-label study to document optimal timing of initiation of dronedarone TreatmEnt after conversion with loading dose of aMIodarone in patients with perSistent Atrial Fibrillation requiring conversion of AF - ARTEMIS AF Loading
• Date of first enrolment: 02/07/2010
• Target sample size: 768
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016818-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: Double blind: Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other: yes Other specify the comparator: arm C Number of treatment arms in the trial: 3

Countries of recruitment

Australia, Austria, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Netherlands, Portugal, Spain, Switzerland, Taiwan, Turkey, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
•Inclusion criteria at screening:
- Male or female adult aged 18 years or more,
- Patient with 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 (Note: patient may already be on anticoagulation treatment),
- Naive of amiodarone treatment in the last three months prior to screening,
- QTcB < 500 ms on 12-lead ECG,
- Patient with at least one cardiovascular risk factor (i.e. age > 70, hypertension, diabetes, prior cerebrovascular disease, left atrial diameter = 50 mm
- Signed written informed consent.

•Inclusion Criteria: to be checked at randomization
- Outpatient and Inpatient. (except patients hospitalized during screening period for SAE).
- Patient 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 one hour before randomization),
- Patient under effective anticoagulation according to ACC/AHA/ESC AF treatment
guidelines [18] verified by INR (target > 2).
INR should be closely monitored after initiating dronedarone in patients taking vitamin K antagonist as per their label
- QTcB < 500 ms and PR < 280 ms on 12-lead ECG,
- Patient having received 28 days ± 2 days of amiodarone.


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:
•Exclusion criteria at screening:
- Contraindication to oral anticoagulation,
- Any 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),
- Patient with permanent AF defined as patients with an AF duration = 6 months (or duration unknown) and attempts to restore sinus rhythm no longer considered by the physician.
- Patient with paroxysmal AF in whom cardioversion is not indicated,
- Bradycardia < 50 beats per minute (bpm) at rest on the 12-lead ECG,
- Clinically overt congestive heart failure:
o with New York Heart Association (NYHA) class III and IV heart failure,
o with LVEF < 35%,
o or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic,
o as well any patient in unstable hemodynamic conditions.
- 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,
- Pregnant women,
- Breastfeeding women,
- Previous (2 preceding months) or current participation in another clinical trial with an investigational drug or with an investigational device,
- Clinically relevant hematologic, underlying hepatobiliary disease, gastrointestinal, pulmonary, endocrinologic, psychiatric, neurological or dermatological disease,
- Severe hepatic impairment,
- Severe renal impairment (creatinine clearance < 30 mL/min),
- Serum potassium <3.5 millimol/liter (mmol/L) (in patients with hypokalemia, potassium deficiency must be corrected before randomization) or > 5.5 mmol/l,
- Magnesemia < 0.8 mml/l (in patient with hypo-magnesemia, magnesium deficiency must be corrected before randomization),
- Unstable angina pectoris (ischemic symptoms during the last 7 days) or recent myocardial infarction (MI) (< 6 weeks),
- First degree family history of sudden cardiac death below age 50 years in the absence of coronary heart disease,
- Second- or third- degree Atrio-Ventricular block or sick sinus syndrome (except when used in conjunction with a functioning pacemaker),
- Ongoing potentially severe symptoms when in AF such as angina pectoris, transient ischemic attacks, stroke, syncope, as judged by the investigator,
- Wolff-Parkinson-White Syndrome,
- Previous ablation for atrial fibrillation or any planned ablation in the next following 2 months.

•Exclusion criteria to be checked at randomization
- Bradycardia < 50 bpm on the 12-lead ECG before randomization,
- Clinically overt congestive heart failure:
o with New York Heart Association (NYHA) class III and IV heart failure,
o with LVEF < 35%,
o or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic,
o as well any patients in unstable hemodynamic conditions.
- Serum potassium <3.5 millimol/liter (mmol/L) (in patients with hypokalemia, potassium deficiency must have been corrected before randomization) or > 5.5 mmol/l,
- Magnesemia < 0.8 mml/l (in patient with hypo-magnesemia, magnesium deficiency must have been corrected before randomization)
- 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,

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Persistant atrial fibrillation requiring conversion of AF
MedDRA version: 14.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Multaq
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DRONEDARONE
CAS Number: 141626360
Current Sponsor code: SR33589
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Primary end point(s): The primary efficacy criterion is the rate of AF recurrences documented by two consecutive scheduled or unscheduled 12-lead ECG or TTEM performed approximately 10 minutes apart

Main Objective: The primary objective of the study is to evaluate the rate of AF recurrences one month after randomization according to different timings of initiation of dronedarone.

Secondary Objective: The secondary efficacy objective is to evaluate the rate of AF recurrences two months after randomization.
To assess the safety of the change from amiodarone to dronedarone
To assess dronedarone safety

Timepoint(s) of evaluation of this end point: The primary efficacy criterion is the rate of AF recurrences one month after randomization according to different timings of initiation of dronedarone.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoint is the rate of AF recurrences.
Secondary safety endpoints

Timepoint(s) of evaluation of this end point: The secondary efficacy endpoint is AF
recurrences two months after randomization.
bradycardia/tachycardia: from V5 to V10
Laboratory tests:
haematology:at V1 and V10.
creatinine: V1, V7 and V10.
INR: V1, V2, V3, V4, V5, V7, V8, V9 and V10.
thyroid function tests: at V1 and V10
hepatic laboratory assessment:V1, V4, V5, V7, V9 and V10.
ECG parameters: at each visit
Adverse events, adverse events of special interest (AESIs), SAEs: all along the study

Secondary ID(s)

2009-016818-24-GB

DRONE_C_03668