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

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 100mg daily (recommended dose) is better than aspirin alone (100mg daily recommended dose) for preventing vascular events such as stroke and heart attack during approximately three years of follow-up in patients with atrial fibrillation associated with at least one major risk factor of vascular event such as elderly, blood pressure increase, history of stroke or transient ischemic attack or left ventricular dysfunction etc. The study will also accept patients with atrial fibrillation and unwilling to take oral anticoagulant therapy.

Intervention(s) in this Clinical Trial

• Drug: clopidogrel (SR25990C)
  • oral administration (tablets)
• Drug: placebo
  • oral administration (tablets)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Clopidogrel + ASA
  • Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)
• Placebo Comparator: Placebo + ASA
  • Matching placebo of clopidogrel 75 mg od plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)

Primary Measures

• First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication
  • Time Frame: expected median follow-up of approximately 3 years
    Safety Issue?: No

Secondary Measures

• Occurrence of Stroke
  • Time Frame: expected median follow-up of approximately 3 years
    Safety Issue?: No
• Death From Any Cause (Cardiovascular and Noncardiovascular)
  • Time Frame: expected median follow-up of approximately 3 years
    Safety Issue?: No
• Adjudicated Major Bleedings
  • Time Frame: expected median follow-up of approximately 3 years
    Safety Issue?: Yes

Inclusion Criteria:

• To be eligible for ACTIVE A patients must have in same time the three following conditions
:
• Evidence of atrial fibrillation either on one current Electrocardiogram (ECG) or two
• ECGs 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 :
• are 75 years greater;
• on treatment for systemic hypertension;
• prior stroke, Transient Ischemic Attack (TIA) or non-Central Nervous System (non-CNS) systemic embolus;
• left ventricular dysfunction with left ventricular ejection fraction (EF) estimated by echocardiogram or angiogram (radionuclide or contrast) to be < 45%;
• 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);
• age 55 to 74 years and either; f1) diabetes mellitus requiring drug therapy, or f2) documented previous myocardial infarction or documented coronary artery disease.
• To have either a contraindication to use an oral anticoagulant treatment or they are unwilling to take an oral anticoagulant treatment.

Exclusion Criteria:

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

• requirement for clopidogrel (such as recent coronary stent procedure)
• requirement for oral anticoagulant (such as prosthetic mechanical heart valve);
• prior intolerance to ASA or clopidogrel;
• documented peptic ulcer disease within the previous 6 months;
• prior intracerebral hemorrhage;
• significant thrombocytopenia; (platelet count < 50 x 10(9)/L)
• psychosocial reason making study participation impractical;
• geographic reason making study participation impractical;
• ongoing alcohol abuse;
• mitral stenosis,
• 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; (severe comorbid condition such that the patient is not expected to survive 6 months;
• patient currently receiving an investigational pharmacologic agent;

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 Investigator: Sanofi-Aventis Industry

Overall Clinical Trial Officials and Contacts

Philippe YUSUF, Prof. Study Chair Hamilton Health Sciences Corporation  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00249873

Study ID Number: EFC4912 A

ClinicalTrials.gov Identifier: NCT00249873

Health Authority: United States: Food and Drug Administration