Pharmacokinetics and Optimal Timing of Dronedarone Initiation Following Long-term Amiodarone in Patients With Paroxysmal or Persistent Atrial Fibrillation (ARTEMIS AF LT)

Sanofi

Status and phase: Completed; Phase 4

Conditions: Atrial Fibrillation

Treatments: Drug: Dronedarone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01199081

2010-019247-19 (EudraCT Number)

DRONE_C_04629

Details and patient eligibility

About

Primary Objective:

• Explore Dronedarone and active metabolite pharmacokinetic (PK) profiles according to different timings of Dronedarone initiation.

Secondary Objective:

• Explore potential PK interaction between Dronedarone and Amiodarone
• Evaluate the rate of Atrial Fibrillation (AF) recurrence during the study period (from randomization up to 60 days after)
• To assess the safety of the change from Amiodarone to Dronedarone and Dronedarone safety

Full description

The maximum study duration per patient is 10 weeks

Enrollment: 154 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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154 participants in 3 patient groups

Group A

Experimental group

Description:

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.

Treatment:

Drug: Dronedarone

Group B

Experimental group

Description:

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.

Treatment:

Drug: Dronedarone

Group C

Experimental group

Description:

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.

Treatment:

Drug: Dronedarone