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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00174785
First received: September 13, 2005
Last updated: January 5, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Atrial Flutter
Drug: dronedarone (SR33589)
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • First Hospitalization for Cardiovascular Reason or Death From Any Cause [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Death From Any Cause [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ] [ Designated as safety issue: No ]
  • First Hospitalization for Cardiovascular Reason [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ] [ Designated as safety issue: No ]
  • Cardiovascular Death [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ] [ Designated as safety issue: No ]

Enrollment: 4628
Study Start Date: June 2005
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dronedarone 400mg bid
Dronedarone 400mg tablets twice daily (bid)
Drug: dronedarone (SR33589)
oral administration (tablets)
Other Name: Multaq®
Placebo Comparator: Placebo
matching placebo tablets
Drug: placebo
oral administration (tablets)

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.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00174785

  Show 37 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: International Clinical Development Sanofi
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: International Clinical Development - Study Director, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00174785     History of Changes
Other Study ID Numbers: EFC5555
Study First Received: September 13, 2005
Results First Received: July 24, 2009
Last Updated: January 5, 2010
Health Authority: United States: Food and Drug Administration
Netherlands: Medicines Evaluation Board (MEB)
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Sanofi:
Mortality, Hospitalization

Additional relevant MeSH terms:
Atrial Fibrillation
Atrial Flutter
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 July 24, 2014