Status:
This study has been completed.
Purpose:
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.
Interventions:
Clopidogrel
Antiplatelet agent
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Placebo
A placebo is a substance or procedure which a patient accepts as a medicine or therapy but which has no specific therapeutic activity for the condition.
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Location(s):
New Jersey,Argentina, Australia, Austria,
Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Italy,
Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Singapore, South Africa, Spain, Sweden,
Switzerland, Taiwan, United Kingdom.
Year Started:
2003
Year Finished:
2008
Design:
Interventional, Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study.
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, TIA or 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;
Patient Involvement:
Patients will be randomized to one of two arms: Drug: clopidogrel (SR25990C) 75 mg once daily in combination with aspirin or Drug: placebo in combination with aspirin.
Primary Outcome:
Primary outcome of the ACTIVE A trial: time to the first outcome of stroke, non-Central Nervous System systemic embolism, myocardial infarction or vascular death
Secondary Outcome:
Secondary outcomes of ACTIVE A trial: major hemorrhage, total mortality and stroke
Results:
At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001). In conclusion, in patients with atrial fibrillation for whom vitamin K-antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage.
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Source of Information:
ClinicalTrials.gov
Presented at ECS 2009 in Spain.
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