Optimal Timing of Dronedarone Initiation After Conversion in Patients With Persistent Atrial Fibrillation (ARTEMIS Load)

Sanofi

Status and phase: Completed; Phase 4

Conditions: Atrial Fibrillation

Treatments: Drug: DRONEDARONE

Study type: Interventional

Funder types: Industry

Identifiers

NCT01140581

2009-016818-24 (EudraCT Number)

DRONE_C_03668

Details and patient eligibility

About

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)

Enrollment: 402 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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402 participants in 3 patient groups

Group A

Experimental group

Description:

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks followed by dronedarone 400 mg twice daily for 8 weeks

Treatment:

Drug: DRONEDARONE

Group B

Experimental group

Description:

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks. Two weeks wash-out followed by dronedarone 400 mg twice daily for 6 weeks

Treatment:

Drug: DRONEDARONE

Group C

Experimental group

Description:

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks. Four weeks wash-out followed by dronedarone 400 mg twice daily for 4 weeks

Treatment:

Drug: DRONEDARONE