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”

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.

Study Type: Interventional

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

Intervention(s) in this Clinical Trial

• Drug: Clopidogrel

Primary Measures

• 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 Measures

• 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.

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sanofi-Aventis

Overall Clinical Trial Officials and Contacts

Salim YUSUF, Prof. Study Chair Hamilton Health Sciences Corporation  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00243178

Study ID Number: EFC4912 W

ClinicalTrials.gov Identifier: NCT00243178

Health Authority: United States: Food and Drug Administration