A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation (ATHENA)

January 5, 2010 updated by: Sanofi

A Placebo-controlled,Double-blind,Parallel Arm Trial to Assess the Efficacy of Dronedarone 400mg Bid for the Prevention of Cardiovascular Hospitalization or Death From Any Cause in Patients With Atrial Fibrillation/Atrial Flutter (AF/AFL)

To assess the efficacy of dronedarone in preventing cardiovascular hospitalization or death from any cause in a population of high-risk patients with atrial fibrillation/atrial flutter (AF/AFL).

To assess that dronedarone is well tolerated in this population.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, multinational, double-blind, randomized, multi-center, placebo-controlled, parallel-group trial evaluating the effects of dronedarone versus placebo (ratio 1:1) over a minimum treatment duration of 12 months and a mean follow-up duration of 1.75 years (in AF/AFL patients). Patients can be included in the study while in atrial fibrillation/flutter or in sinus rhythm if conversion has occurred either spontaneously or following a procedure such as electrical cardioversion (or overdrive pacing) or administration of an antiarrhythmic drug.After randomization all patients will be followed until the common study end date; the last patient included in the study will be followed for 1 year. Visits will be at baseline, after 7 days, after 14 days, after one month, after three months and then every three months until end of the study. At each visit patients will be asked for the occurrence of hospitalizations or other events since the last visit. The study will be monitored by an independent Data Monitoring Committee (DMC) for safety, tolerability and efficacy.

Study Type

Interventional

Enrollment (Actual)

4628

Phase

  • Phase 3

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

  • Argentina
      • Buenos Aires, Argentina
        • Sanofi-Aventis Administrative Office
  • Australia
      • New South Wales, Australia
        • Sanofi-Aventis Administrative Office
  • Austria
      • Wien, Austria
        • Sanofi-Aventis Administrative Office
  • Belgium
      • Diegem, Belgium
        • Sanofi-Aventis Administrative Office
  • Canada
      • Laval, Canada
        • Sanofi-Aventis Administrative Office
  • Chile
      • Santiago, Chile
        • Sanofi-Aventis Administrative Office
  • China
      • Shangaï, China
        • Sanofi-Aventis Administrative Office
  • Czech Republic
      • Praha, Czech Republic
        • Sanofi-Aventis Administrative Office
  • Finland
      • Helsinki, Finland
        • Sanofi-Aventis Administrative Office
  • Germany
      • Berlin, Germany
        • Sanofi-Aventis Administrative Office
  • Greece
      • Athens, Greece
        • Sanofi-Aventis Administrative Office
  • Hong Kong
      • Causeway Bay, Hong Kong
        • Sanofi-Aventis Administrative Office
  • Hungary
      • Budapest, Hungary
        • Sanofi-Aventis Administrative Office
  • India
      • Mumbai, India
        • Sanofi-Aventis Administrative Office
  • Israel
      • Natanya, Israel
        • Sanofi-Aventis Administrative Office
  • Italy
      • Milano, Italy
        • Sanofi-Aventis Administrative Office
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Sanofi-Aventis Administrative Office
  • Malaysia
      • Kuala Lumpur, Malaysia
        • Sanofi-Aventis Administrative Office
  • Mexico
      • Mexico, Mexico
        • Sanofi-Aventis Administrative Office
  • Morocco
      • Casablanca, Morocco
        • Sanofi-Aventis Administrative Office
  • Netherlands
      • Gouda, Netherlands
        • Sanofi-Aventis Administrative Office
  • New Zealand
      • Macquarie Park, New Zealand
        • Sanofi-Aventis Administrative Office
  • Norway
      • Lysaker, Norway
        • Sanofi-Aventis Administrative Office
  • Philippines
      • Makati City, Philippines
        • Sanofi-Aventis Administrative Office
  • Poland
      • Warszawa, Poland
        • Sanofi-Aventis Administrative Office
  • Portugal
      • Porto Salvo, Portugal
        • Sanofi-Aventis Administrative Office
  • Russian Federation
      • Moscow, Russian Federation
        • Sanofi-Aventis Administrative Office
  • Singapore
      • Singapore, Singapore
        • Sanofi-Aventis Administrative Office
  • South Africa
      • Midrand, South Africa
        • Sanofi-Aventis Administrative Office
  • Spain
      • Barcelona, Spain
        • Sanofi-Aventis Administrative Office
  • Sweden
      • Bromma, Sweden
        • Sanofi-Aventis Administrative Office
  • Taiwan
      • Taipei, Taiwan
        • Sanofi-Aventis Administrative Office
  • Thailand
      • Bangkok, Thailand
        • Sanofi-Aventis Administrative Office
  • Tunisia
      • Megrine, Tunisia
        • Sanofi-Aventis Administrative Office
  • Turkey
      • Istanbul, Turkey
        • Sanofi-Aventis Administrative Office
  • United Kingdom
      • Guildford Surrey, United Kingdom
        • Sanofi-Aventis Administrative Office
  • United States
    • New Jersey
      • Bridgewater, New Jersey, United States, 08807
        • Sanofi-Aventis Administrative Office

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

70 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 1. Patients aged 75 years or older (70 years before protocol amendment 1), or patients aged at least 70 years (any age before protocol amendment 1) with one or more of the following risk factors at baseline:

    • Hypertension (taking antihypertensive drugs of at least two different classes)
    • Diabetes
    • Prior cerebrovascular accident (stroke or transient ischemic attack) or systemic embolism
    • Left atrium diameter greater than or equal to 50 mm by echocardiography
    • Left ventricular ejection fraction less than 0.40 by 2D-echocardiography (two-dimensional echocardiography)
  • 2. Availability of one electrocardiogram (ECG) within the last 6 months, showing that the patient was or is in AF/AFL
  • 3. Availability of one ECG within the last 6 months, showing that the patient was or is in sinus rhythm

Exclusion Criteria:

General criteria:

  • 1. Refusal or inability to give informed consent to participate in the study
  • 2. Any non cardiovascular illness or disorder that could preclude participation or severely limit survival including cancer with metastasis and organ transplantation requiring immune suppression
  • 3. Pregnant women (pregnancy test must be negative) or women of childbearing potential not on adequate birth control: only women with a highly effective method of contraception [oral contraception or intra-uterine device (IUD)] or sterile can be randomized.
  • 4. Breastfeeding women
  • 5. Previous (2 preceding months) or current participation in another clinical trial with an investigational drug (under development) or with an investigational device
  • 6. Previous participation in this trial

Criteria Related to a cardiac condition:

  • 7. Patients in permanent atrial fibrillation
  • 8. Patients in unstable hemodynamic condition such as acute pulmonary edema within 12 hours prior to start of study medication; cardiogenic shock; treatment with intra-venous pressor agents; patients on respirator; congestive heart failure of stage NYHA IV (New York Heart Association classification) within the last 4 weeks; uncorrected, hemodynamically significant primary obstructive valvular disease; hemodynamically significant obstructive cardiomyopathy; a cardiac operation or revascularization procedure within 4 weeks preceding randomization
  • 9. Planned major non-cardiac or cardiac surgery or procedures including surgery for valvular heart disease, coronary artery bypass graft (CABG) , percutaneous coronary intervention (PCI) , or on urgent cardiac transplantation list
  • 10. Acute myocarditis or constrictive pericarditis
  • 11. Bradycardia < 50 bpm and/or PR-interval > 0.28 sec on the last 12-lead ECG
  • 12. Significant sinus node disease (documented pause of 3 seconds or more) or 2nd or 3rd degree atrioventricular block (AV-block) unless treated with a pacemaker

Criteria Related to Concomitant Medications:

  • 13. Need of a concomitant medication that is prohibited in this trial, including the requirement for Vaughan Williams Class I and III anti-arrhythmic drugs, that would preclude the use of study drug during the planned study period

Criteria Related to Laboratory Abnormalities:

  • 14. Plasma potassium < 3.5 mmol/l (as anti-arrhythmic drugs can be arrhythmogenic in patients with hypokalemia, this must be corrected prior to randomization)
  • 15. A calculated Glomerular Filtration Rate (GFR) at baseline <10 ml/min using the Cockroft Gault formula

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
matching placebo tablets
Drug: placebo
oral administration (tablets)
Experimental: Dronedarone 400mg bid
Dronedarone 400mg tablets twice daily (bid)
Drug: dronedarone (SR33589)
oral administration (tablets)
Other Names:
  • Multaq®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
First Hospitalization for Cardiovascular Reason or Death From Any Cause
Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years
The primary event is the first hospitalization for cardiovascular reason or death from any cause, whichever is earlier, as assessed by the investigator. The primary efficacy analysis is performed on the time from randomization to this primary event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
minimum follow-up duration: 1 year ; maximum: 2.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death From Any Cause
Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years
The considered event is death from any cause. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
minimum follow-up duration: 1 year ; maximum: 2.5 years
First Hospitalization for Cardiovascular Reason
Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years
The considered event is the first hospitalization for cardiovascular reason, as assessed by the Investigator. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
minimum follow-up duration: 1 year ; maximum: 2.5 years
Cardiovascular Death
Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years
The considered event is cardiovascular death, as assessed by the Investigator. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
minimum follow-up duration: 1 year ; maximum: 2.5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adjudicated Cardiovascular Death
Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years
The considered event is cardiovascular death, as assessed by the blinded adjudication of the Steering Committee. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
minimum follow-up duration: 1 year ; maximum: 2.5 years

Collaborators and Investigators

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

Sponsor

Sanofi

Investigators

  • Study Director: International Clinical Development, 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

Helpful Links

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

June 1, 2005

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Estimate)

January 12, 2010

Last Update Submitted That Met QC Criteria

January 5, 2010

Last Verified

January 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EFC5555

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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