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

January 20, 2012 updated by: Sanofi

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.

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

402

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia, 5000
        • Investigational Site Number 009
      • Ballarat, Australia, 3350
        • Investigational Site Number 013
      • Garran, Australia, 2605
        • Investigational Site Number 002
      • Herston, Australia, 4006
        • Investigational Site Number 007
      • Hobart, Australia, 7000
        • Investigational Site Number 012
      • Liverpool, Australia, 2170
        • Investigational Site Number 006
      • Maroubra, Australia, 2035
        • Investigational Site Number 010
      • Nedlands, Australia, 6009
        • Investigational Site Number 001
      • New Lambton, Australia, 2305
        • Investigational Site Number 004
      • Redcliffe, Australia, 4020
        • Investigational Site Number 008
      • South Brisbane, Australia, 4101
        • Investigational Site Number 011
      • Southport, Australia, 4215
        • Investigational Site Number 005
      • Woolloongabba, Australia, 4102
        • Investigational Site Number 003
  • Austria
      • Braunau, Austria, 5280
        • Investigational Site Number 040-006
      • Innsbruck, Austria, 6020
        • Investigational Site Number 040-007
      • Linz, Austria, 4010
        • Investigational Site Number 040-002
      • Mödling, Austria, 2340
        • Investigational Site Number 040-001
      • Vienna, Austria
        • Investigational Site Number 040-003
      • Wien, Austria, 1090
        • Investigational Site Number 040-005
      • Wien, Austria
        • Investigational Site Number 040-004
  • Estonia
      • Tallinn, Estonia, 10138
        • Investigational Site Number 233001
  • Finland
      • Hyvinkää, Finland, 05850
        • Investigational Site Number 246-001
      • Hyvinkää, Finland, 05850
        • Investigational Site Number 246-002
      • Pori, Finland, 28210
        • Investigational Site Number 246-004
      • Seinäjoki, Finland, 60220
        • Investigational Site Number 246-003
  • France
      • Avignon Cedex 9, France, 84902
        • Investigational Site Number 250-006
      • BEZIERS Cedex, France, 34525
        • Investigational Site Number 250-009
      • Bron, France, 69677
        • Investigational Site Number 250-002
      • Cholet, France, 49300
        • Investigational Site Number 250-007
      • Lyon Cedex 03, France, 69275
        • Investigational Site Number 250-008
      • NIMES Cedex 9, France, 30029
        • Investigational Site Number 250-010
      • POITIERS Cedex, France, 86021
        • Investigational Site Number 250-003
      • Toulouse Cedex 3, France, 31076
        • Investigational Site Number 250-004
      • Valence Cedex 9, France, 26953
        • Investigational Site Number 250-005
      • Vandoeuvre Les Nancy, France, 54511
        • Investigational Site Number 250-001
  • Germany
      • Berlin, Germany, 13055
        • Investigational Site Number 276-003
      • Bernau, Germany, 16321
        • Investigational Site Number 276-006
      • Bonn, Germany, 53115
        • Investigational Site Number 276-001
      • Dresden, Germany, 01099
        • Investigational Site Number 276-011
      • Frankfurt am Main, Germany, 60594
        • Investigational Site Number 276-010
      • Hamburg, Germany, 22041
        • Investigational Site Number 276-002
      • Hamburg, Germany, 22527
        • Investigational Site Number 276-008
      • Heidenau, Germany, 01809
        • Investigational Site Number 276-009
      • Kiel, Germany, 24105
        • Investigational Site Number 276-004
      • Ludwigsburg, Germany, 71634
        • Investigational Site Number 276-005
      • Paderborn, Germany, 33098
        • Investigational Site Number 276-007
  • Israel
      • Ashkelon, Israel
        • Investigational Site Number 376002
      • Beer Yaakov, Israel
        • Investigational Site Number 376001
  • Italy
      • Ancona, Italy, 60100
        • Investigational Site Number 380-005
      • Barga, Italy, 55051
        • Investigational Site Number 380-002
      • Catania, Italy, 95124
        • Investigational Site Number 380-004
      • Como, Italy, 22100
        • Investigational Site Number 380-001
      • Cortona, Italy, 52042
        • Investigational Site Number 380-006
      • Mestre, Italy, 30174
        • Investigational Site Number 380-011
      • Palermo, Italy, 90127
        • Investigational Site Number 380-010
      • Roma, Italy, 00168
        • Investigational Site Number 380-007
      • Roma, Italy, 00169
        • Investigational Site Number 380-003
      • San Daniele Del Friuli, Italy, 33038
        • Investigational Site Number 380-009
      • Varese, Italy, 21100
        • Investigational Site Number 380-012
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Investigational Site Number 410002
      • Seoul, Korea, Republic of
        • Investigational Site Number 410004
      • Seoul, Korea, Republic of, 152-703
        • Investigational Site Number 410001
      • Seoul, Korea, Republic of
        • Investigational Site Number 410003
      • Seoul, Korea, Republic of
        • Investigational Site Number 410005
      • Suwon, Korea, Republic of, 443-721
        • Investigational Site Number 410006
  • Mexico
      • Aguascalientes, Mexico, 20230
        • Investigational Site Number 484017
      • Chihuahua, Mexico, 31238
        • Investigational Site Number 484012
      • Guadalajara, Mexico, 44200
        • Investigational Site Number 484008
      • Guadalajara, Mexico, 44600
        • Investigational Site Number 484009
      • Guadalajara, Mexico, 44600
        • Investigational Site Number 484015
      • Leon, Mexico, 37150
        • Investigational Site Number 484002
      • Mexico, Mexico, 06140
        • Investigational Site Number 484016
      • Mexico, Mexico, 07760
        • Investigational Site Number 484004
      • Monterrey, Mexico, 64460
        • Investigational Site Number 484005
      • Monterrey, Mexico, 64710
        • Investigational Site Number 484003
      • Queretaro, Mexico, 76000
        • Investigational Site Number 484001
      • Saltillo, Mexico, 25230
        • Investigational Site Number 484013
      • Tijuana, Mexico, 22450
        • Investigational Site Number 484011
  • Netherlands
      • Amsterdam, Netherlands
        • Investigational Site Number 528003
      • Goes, Netherlands
        • Investigational Site Number 528005
      • Groningen, Netherlands
        • Investigational Site Number 528002
      • Maastricht, Netherlands
        • Investigational Site Number 528001
      • Rotterdam, Netherlands
        • Investigational Site Number 528004
  • Portugal
      • Amadora, Portugal, 2720-276
        • Investigational Site Number 620005
      • Lisboa, Portugal, 1169-024
        • Investigational Site Number 620001
  • Spain
      • El Palmar (MURCIA), Spain, 30120
        • Investigational Site Number 724004
      • Hospitalet de Llobregat, Spain, 08907
        • Investigational Site Number 724005
      • LLeida, Spain
        • Investigational Site Number 724003
      • La Coruña, Spain, 15006
        • Investigational Site Number 724008
      • Madrid, Spain, 28040
        • Investigational Site Number 724001
      • Madrid, Spain, 28034
        • Investigational Site Number 724010
      • Majadahonda, Spain, 28222
        • Investigational Site Number 724002
      • Sevilla, Spain, 41071
        • Investigational Site Number 724006
      • Tarragona, Spain, 43007
        • Investigational Site Number 724007
      • Valencia, Spain, 46014
        • Investigational Site Number 724009
  • Switzerland
      • Basel, Switzerland, 4031
        • Investigational Site Number 756001
      • St.Gallen, Switzerland, 9007
        • Investigational Site Number 756002
  • Taiwan
      • Kaohsiung, Taiwan, 807
        • Investigational Site Number 158006
      • Kaohsiung Hsien,, Taiwan
        • Investigational Site Number 158005
      • Taichung, Taiwan, 402
        • Investigational Site Number 158004
      • Taichung, Taiwan, 407
        • Investigational Site Number 158003
      • Taichung City, Taiwan
        • Investigational Site Number 158009
      • Taipei, Taiwan
        • Investigational Site Number 158001
      • Taipei, Taiwan, 100
        • Investigational Site Number 158002
      • Taipei, Taiwan
        • Investigational Site Number 158008
      • Tao Yuan Hsien, Taiwan
        • Investigational Site Number 158007
  • United Kingdom
      • Belfast, United Kingdom, BT126BA
        • Investigational Site Number 826006
      • Bournemouth, United Kingdom, BH77DW
        • Investigational Site Number 826-005
      • Carshalton, United Kingdom, SM51AA
        • Investigational Site Number 826-001
      • Gloucester, United Kingdom, GL13NN
        • Investigational Site Number 826-002
      • Wrexham, United Kingdom, LL137TD
        • Investigational Site Number 826-007

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AF recurrences
Time Frame: one month after randomization
two consecutives 12-lead ECG or Trans-Telephonic ECG monitoring (TTEM) approximatively 10 minutes apart and both showing AF
one month after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AF recurrences
Time Frame: two months after randomization
two months after randomization
Symptomatic bradycardia
Time Frame: two months after randomization
Heart rate at rest < 50 beats per minute
two months after randomization
Tachycardia
Time Frame: two months after randomization
Heart rate at rest > 120 beats per minute
two months after randomization
Dronedarone and amiodarone concentrations in plasma
Time Frame: 3 hours, 1 week, 2 weeks and 4 weeks after 1st Dronedarone intake
Limited to a subset of countries
3 hours, 1 week, 2 weeks and 4 weeks after 1st Dronedarone intake

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

June 8, 2010

First Submitted That Met QC Criteria

June 8, 2010

First Posted (Estimate)

June 9, 2010

Study Record Updates

Last Update Posted (Estimate)

January 23, 2012

Last Update Submitted That Met QC Criteria

January 20, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DRONE_C_03668
  • 2009-016818-24 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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