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

Atrial Fibrillation Clinical Trial

— ATHENA  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00174785
• Other study ID #: EFC5555
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: January 5, 2010
• Start date: June 2005
• Est. completion date: March 2008

Study information

• Verified date: January 2010
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationNetherlands: Medicines Evaluation Board (MEB)France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4628
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 70 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Flutter

Intervention

Drug:
• dronedarone (SR33589)
oral administration (tablets)
• placebo
oral administration (tablets)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  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, 

References & Publications (2)

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. — View Citation

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. Erra — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First Hospitalization for Cardiovascular Reason or Death From Any Cause		minimum follow-up duration: 1 year ; maximum: 2.5 years	No
Secondary	Death From Any Cause		minimum follow-up duration: 1 year ; maximum: 2.5 years	No
Secondary	First Hospitalization for Cardiovascular Reason		minimum follow-up duration: 1 year ; maximum: 2.5 years	No
Secondary	Cardiovascular Death		minimum follow-up duration: 1 year ; maximum: 2.5 years	No

External Links

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