Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE W)

Condition(s) targeted: Atrial Fibrillation; Vascular Risk

Intervention: Clopidogrel (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Sanofi-Aventis

Official(s) and/or principal investigator(s):
Salim YUSUF, Prof., Study Chair, Affiliation: Hamilton Health Sciences Corporation

The purpose of this study is to determine if the combination of Clopidogrel 75mg once daily (od) plus aspirin at 100mg daily (recommended dose) is as effective as oral anticoagulation therapy with a lower risk of bleeding in patients with atrial fibrillation associated with at least one major cardiovascular risk factor. Primary objectives :The combination of clopidogrel plus aspirin compared to adjusted dose (INR between 2. 0 and 3. 3) oral anticoagulation (a vitamin K antagonist) will result in the same risk of the composite outcome of stroke, non-CNS systemic embolism, myocardial infarction or vascular death in patients with atrial fibrillation. The secondary objective is to establish whether or not aspirin plus clopidogrel has a lower risk of hemorrhage than standard anticoagulation therapy.

Official title: A Parallel Randomized Controlled Evaluation of Clopidogrel Plus Aspirin, With Factorial Evaluation of Irbesartan, for the Prevention of Vascular Events, in Patients With Atrial Fibrillation

Study design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: The primary outcome will be the time to the first occurrence of stroke, non-CNS systemic embolism, myocardial infarction or vascular death during approximately three years of follow-up.

Secondary outcome:

The secondary outcomes will be :

- Major hemorrhage, total mortality and stroke.The other outcomes will include individual components of the primary outcome and all safety criteria including serious adverse events.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

Evidence of atrial fibrillation either on one current Electrocardiogram (ECG) or on two ECG recorded at two weeks a part during 6 months prior to study enrollment.

Evidence of high risk of vascular events: at least one of the following risk criteria must be present:

- a) are 75 years or greater;

- b) on treatment for systemic hypertension;

- c) prior stroke, TIA or non-CNS systemic embolus;

- d) left ventricular dysfunction with left ventricular ejection fraction (EF) estimated

by echocardiogram or angiogram (radionuclide or contrast) to be < 45%;

- e) peripheral vascular disease (previous peripheral artery revascularization, limb and

foot amputation, or the combination of current intermittent claudication and ankle arm systolic blood pressure ratio <0. 9)

- f) age 55 to 74 years and either; diabetes mellitus requiring drug therapy, or

documented previous myocardial infarction or documented coronary artery disease.

Exclusion Criteria:

Patients will be excluded from ACTIVE if any of the following are present :

- a) requirement for clopidogrel (such as recent coronary stent procedure)

- b) requirement for oral anticoagulant (such as prosthetic mechanical heart valve);

- c) prior intolerance to ASA or clopidogrel;

- d) documented peptic ulcer disease within the previous 6 months;

- e) prior intracerebral hemorrhage;

- f) significant thrombocytopenia; (platelet count <50 x 10(9)/L)

- g) psychosocial reason making study participation impractical;

- h) geographic reason making study participation impractical;

- i) ongoing alcohol abuse;

- j) mitral stenosis,

- k) pregnant or nursing woman or woman of child bearing potential and not on effective

birth control for at least one month prior to start of study or not willing to continue on birth control for duration of study;

- l) severe comorbid condition such that the patient is not expected to survive 6

months;

- m) patient currently receiving an investigational pharmacologic agent;

- n) requirement for chronic (> 3 months) non-COX-2 inhibitor NSAID therapy.

Sanofi-Aventis Administrative Office, Macquarie Park, Australia

Sanofi-Aventis Administrative Office, Wien, Austria

Sanofi-Aventis Administrative Office, Diegem, Belgium

Sanofi-Aventis Administrative Office, Sao Paulo, Brazil

Sanofi-Aventis Administrative Office, Laval, Canada

Sanofi-Aventis Administrative Office, Santiago, Chile

Sanofi-Aventis Administrative Office, Praha, Czech Republic

Sanofi-Aventis Administrative Office, Horsholm, Denmark

Sanofi-Aventis Administrative Office, Helsinki, Finland

Sanofi-Aventis Administrative Office, Paris, France

Sanofi-Aventis Administrative Office, Berlin, Germany

Sanofi-Aventis Administrative Office, Athens, Greece

Sanofi-Aventis Administrative Office, Causeway Bay, Hong Kong

Sanofi-Aventis Administrative Office, Budapest, Hungary

Sanofi-Aventis Administrative Office, Natanya, Israel

Sanofi-Aventis Administrative Office, Milano, Italy

Sanofi-Aventis Administrative Office, Kuala Lumpur, Malaysia

Sanofi-Aventis Administrative Office, Mexico, Mexico

Sanofi-Aventis Administrative Office, Gouda, Netherlands

Sanofi-Aventis Administrative Office, Lysaker, Norway

Sanofi-Aventis Administrative Office, Warszawa, Poland

Sanofi-Aventis Administrative Office, Porto Salvo, Portugal

Sanofi-Aventis Administrative Office, Moscow, Russian Federation

Sanofi-Aventis Administrative Office, Singapore, Singapore

Sanofi-Aventis Administrative Office, Midrand, South Africa

Sanofi-Aventis Administrative Office, Barcelona, Spain

Sanofi-Aventis Administrative Office, Bromma, Sweden

Sanofi-Aventis Administrative Office, Geneva, Switzerland

Sanofi-Aventis Administrative Office, Taipei, Taiwan

Sanofi-Aventis Administrative Office, Istanbul, Turkey

Sanofi-Aventis Administrative Office, Guildford Surrey, United Kingdom

Sanofi-Aventis Administrative Office, Bridgewater, New Jersey 08807, United States

Starting date: July 2003
Ending date: November 2005
Last updated: April 18, 2008