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

Tracking Information
First Submitted Date ICMJE	September 13, 2005
First Posted Date ICMJE	September 15, 2005
Results First Submitted Date	July 24, 2009
Results First Posted Date	December 23, 2009
Last Update Posted Date	January 12, 2010
Study Start Date ICMJE	June 2005
Actual Primary Completion Date	March 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 17, 2009)	First Hospitalization for Cardiovascular Reason or Death From Any Cause [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ]
Original Primary Outcome Measures ICMJE; (submitted: September 13, 2005)	The primary efficacy variable will be the time from randomization to death from any cause or hospitalization for cardiovascular reason, whichever is earlier.
Change History	Complete list of historical versions of study NCT00174785 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 17, 2009)	Death From Any Cause [ Time Frame: 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 ]; Cardiovascular Death [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ]
Original Secondary Outcome Measures ICMJE; (submitted: September 13, 2005)	Secondary criteria are:; - Death from any cause; - Cardiovascular death; - Hospitalization for cardiovascular reasons
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation
Official Title ICMJE	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)
Brief Summary	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.
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 ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
Condition ICMJE	Atrial Fibrillation; Atrial Flutter
Intervention ICMJE	Drug: dronedarone (SR33589) oral administration (tablets) Other Name: Multaq®; Drug: placebo oral administration (tablets)
Study Arms	Experimental: Dronedarone 400mg bid Dronedarone 400mg tablets twice daily (bid) Intervention: Drug: dronedarone (SR33589); Placebo Comparator: Placebo matching placebo tablets Intervention: Drug: placebo
Publications *	Hohnloser SH, Connolly SJ, Crijns HJ, Page RL, Seiz W, Torp-Petersen C. Rationale and design of ATHENA: A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter. J Cardiovasc Electrophysiol. 2008 Jan;19(1):69-73. Epub 2007 Nov 21.; Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen C, Connolly SJ; ATHENA Investigators. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009 Feb 12;360(7):668-78. doi: 10.1056/NEJMoa0803778. Erratum in: N Engl J Med. 2009 Jun 4;360(23):2487. Erratum in: N Engl J Med. 2011 Apr 14;364(15):1481.; Åkerborg Ö, Nilsson J, Bascle S, Lindgren P, Reynolds M. Cost-effectiveness of dronedarone in atrial fibrillation: results for Canada, Italy, Sweden, and Switzerland. Clin Ther. 2012 Aug;34(8):1788-802. doi: 10.1016/j.clinthera.2012.06.007. Epub 2012 Jul 6.; Torp-Pedersen C, Crijns HJ, Gaudin C, Page RL, Connolly SJ, Hohnloser SH; ATHENA Investigators. Impact of dronedarone on hospitalization burden in patients with atrial fibrillation: results from the ATHENA study. Europace. 2011 Aug;13(8):1118-26. doi: 10.1093/europace/eur102. Epub 2011 May 15.; Page RL, Connolly SJ, Crijns HJ, van Eickels M, Gaudin C, Torp-Pedersen C, Hohnloser SH; ATHENA Investigators. Rhythm- and rate-controlling effects of dronedarone in patients with atrial fibrillation (from the ATHENA trial). Am J Cardiol. 2011 Apr 1;107(7):1019-22. doi: 10.1016/j.amjcard.2010.11.028. Epub 2011 Feb 4.; Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen C, Connolly SJ; ATHENA Investigators. Dronedarone in patients with congestive heart failure: insights from ATHENA. Eur Heart J. 2010 Jul;31(14):1717-21. doi: 10.1093/eurheartj/ehq113. Epub 2010 Apr 30.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 2, 2008)	4628
Original Enrollment ICMJE; (submitted: September 13, 2005)	3700
Actual Study Completion Date	March 2008
Actual Primary Completion Date	March 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	70 Years and older (Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Austria, Belgium, Canada, Chile, China, Czech Republic, Finland, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Morocco, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Tunisia, Turkey, United Kingdom, United States
Removed Location Countries	France
Administrative Information
NCT Number ICMJE	NCT00174785
Other Study ID Numbers ICMJE	EFC5555
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	International Clinical Development - Study Director, sanofi-aventis
Study Sponsor ICMJE	Sanofi
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: International Clinical Development Sanofi
PRS Account	Sanofi
Verification Date	January 2010
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP