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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00174785




Registration number
NCT00174785
Ethics application status
Date submitted
13/09/2005
Date registered
15/09/2005
Date last updated
12/01/2010

Titles & IDs
Public title
A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation
Scientific 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)
Secondary ID [1] 0 0
EFC5555
Universal Trial Number (UTN)
Trial acronym
ATHENA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 0 0
Atrial Flutter 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Cardiovascular 0 0 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - dronedarone (SR33589)
Treatment: Drugs - placebo

Experimental: Dronedarone 400mg bid - Dronedarone 400mg tablets twice daily (bid)

Placebo comparator: Placebo - matching placebo tablets


Treatment: Drugs: dronedarone (SR33589)
oral administration (tablets)

Treatment: Drugs: placebo
oral administration (tablets)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
First Hospitalization for Cardiovascular Reason or Death From Any Cause
Timepoint [1] 0 0
minimum follow-up duration: 1 year ; maximum: 2.5 years
Secondary outcome [1] 0 0
Death From Any Cause
Timepoint [1] 0 0
minimum follow-up duration: 1 year ; maximum: 2.5 years
Secondary outcome [2] 0 0
First Hospitalization for Cardiovascular Reason
Timepoint [2] 0 0
minimum follow-up duration: 1 year ; maximum: 2.5 years
Secondary outcome [3] 0 0
Cardiovascular Death
Timepoint [3] 0 0
minimum follow-up duration: 1 year ; maximum: 2.5 years

Eligibility
Key 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
Minimum age
70 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2008
Sample size
Target
Accrual to date
Final
4628
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis Administrative Office - New South Wales
Recruitment postcode(s) [1] 0 0
- New South Wales
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Austria
State/province [3] 0 0
Wien
Country [4] 0 0
Belgium
State/province [4] 0 0
Diegem
Country [5] 0 0
Canada
State/province [5] 0 0
Laval
Country [6] 0 0
Chile
State/province [6] 0 0
Santiago
Country [7] 0 0
China
State/province [7] 0 0
Shangaï
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Praha
Country [9] 0 0
Finland
State/province [9] 0 0
Helsinki
Country [10] 0 0
Germany
State/province [10] 0 0
Berlin
Country [11] 0 0
Greece
State/province [11] 0 0
Athens
Country [12] 0 0
Hong Kong
State/province [12] 0 0
Causeway Bay
Country [13] 0 0
Hungary
State/province [13] 0 0
Budapest
Country [14] 0 0
India
State/province [14] 0 0
Mumbai
Country [15] 0 0
Israel
State/province [15] 0 0
Natanya
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seoul
Country [18] 0 0
Malaysia
State/province [18] 0 0
Kuala Lumpur
Country [19] 0 0
Mexico
State/province [19] 0 0
Mexico
Country [20] 0 0
Morocco
State/province [20] 0 0
Casablanca
Country [21] 0 0
Netherlands
State/province [21] 0 0
Gouda
Country [22] 0 0
New Zealand
State/province [22] 0 0
Macquarie Park
Country [23] 0 0
Norway
State/province [23] 0 0
Lysaker
Country [24] 0 0
Philippines
State/province [24] 0 0
Makati City
Country [25] 0 0
Poland
State/province [25] 0 0
Warszawa
Country [26] 0 0
Portugal
State/province [26] 0 0
Porto Salvo
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Moscow
Country [28] 0 0
Singapore
State/province [28] 0 0
Singapore
Country [29] 0 0
South Africa
State/province [29] 0 0
Midrand
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Sweden
State/province [31] 0 0
Bromma
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taipei
Country [33] 0 0
Thailand
State/province [33] 0 0
Bangkok
Country [34] 0 0
Tunisia
State/province [34] 0 0
Megrine
Country [35] 0 0
Turkey
State/province [35] 0 0
Istanbul
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Guildford Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00174785
Trial related presentations / 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. doi: 10.1111/j.1540-8167.2007.01016.x. 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. N Engl J Med. 2011 Apr 14;364(15):1481.
Handelsman Y, Bunch TJ, Rodbard HW, Steinberg BA, Thind M, Bigot G, Konigsberg L, Wieloch M, Kowey PR. Impact of dronedarone on patients with atrial fibrillation and diabetes: A sub-analysis of the ATHENA and EURIDIS/ADONIS studies. J Diabetes Complications. 2022 Jul;36(7):108227. doi: 10.1016/j.jdiacomp.2022.108227. Epub 2022 Jun 8.
Vamos M, Oldgren J, Nam GB, Lip GYH, Calkins H, Zhu J, Ueng KC, Ludwigs U, Wieloch M, Stewart J, Hohnloser SH. Dronedarone vs. placebo in patients with atrial fibrillation or atrial flutter across a range of renal function: a post hoc analysis of the ATHENA trial. Eur Heart J Cardiovasc Pharmacother. 2022 Jun 8;8(4):363-371. doi: 10.1093/ehjcvp/pvab090.
Akerborg O, 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.
Public notes

Contacts
Principal investigator
Name 0 0
International Clinical Development
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00174785