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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01140581
First received: June 8, 2010
Last updated: January 20, 2012
Last verified: January 2012
History of Changes
  Purpose

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)

Condition Intervention Phase
Atrial Fibrillation
 Drug: DRONEDARONE
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • AF recurrences [ Time Frame: one month after randomization ] [ Designated as safety issue: No ]
    two consecutives 12-lead ECG or Trans-Telephonic ECG monitoring (TTEM) approximatively 10 minutes apart and both showing AF


Secondary Outcome Measures:
  • AF recurrences [ Time Frame: two months after randomization ] [ Designated as safety issue: No ]
  • Symptomatic bradycardia [ Time Frame: two months after randomization ] [ Designated as safety issue: No ]
    Heart rate at rest < 50 beats per minute

  • Tachycardia [ Time Frame: two months after randomization ] [ Designated as safety issue: No ]
    Heart rate at rest > 120 beats per minute

  • Dronedarone and amiodarone concentrations in plasma [ Time Frame: 3 hours, 1 week, 2 weeks and 4 weeks after 1st Dronedarone intake ] [ Designated as safety issue: No ]
    Limited to a subset of countries


Enrollment: 402
Study Start Date: September 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
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
 Drug: DRONEDARONE
Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg
Experimental: Group B
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
 Drug: DRONEDARONE
Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg
Experimental: Group C
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
 Drug: DRONEDARONE
Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01140581

  Show 111 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01140581     History of Changes
Other Study ID Numbers: DRONE_C_03668, 2009-016818-24
Study First Received: June 8, 2010
Last Updated: January 20, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Amiodarone
Anti-Arrhythmia Agents
 Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on May 16, 2013