The goal of this study is to learn if combination antiplatelet therapy (aspirin and clopidogrel) is more effective than aspirin alone for the prevention of recurrent stroke and cognitive decline, and if intensive blood pressure control is associated with fewer recurrent strokes and cognitive decline.
On July 21, 2011 the DSMB recommended terminating the anti platelet arm of the study due to an imbalance of overall and major non-CNS hemorrhagic SAE's and total deaths in the investigational anti platelet combination of aspirin + clopidogrel and an interim statistical analysis that demonstrated futility in the investigational anti platelet arm. It was recommended that patients be continued on standard care of aspirin mono therapy until their study close-out visit. Also, recommended the continuation and completion of the plood pressure arm following the protocol.
Stroke is damage to the brain caused by problems in the blood vessels. Strokes often cause paralysis, loss of sensation and speech, and other problems. A lacunar or small Subcortical stroke affects the inner part of the brain causing small "pea sized" areas of damage due to blockage of small blood vessels within the brain.
This multi-center study will recruit 3000 participants (20 percent of whom will be Hispanic) to find out if using aspirin and clopidogrel is more effective than using aspirin alone to prevent recurrent stroke in patients with lacunar stroke confirmed by MRI, and if lowering a patient's blood pressure below the usual limits will also help prevent recurrent stroke and maintain thinking ability. Both aspirin and clopidogrel are widely-used for blood clotting and stroke prevention. Investigators intend to find out if using the drugs together is more effective than using aspirin alone.
Participants will be randomly assigned to one of 2 types of treatment: either aspirin alone or the combination of aspirin and clopidogrel. In addition, participants will be assigned to one of 2 groups of blood pressure control. The difference between the two groups is the target level of systolic blood pressure—either 130-149 or below 130. The goal of the blood pressure aspect of this trial is to find out if lowering blood pressure after stroke helps to prevent recurrent stroke and preserves cognition.
- Aspirin (stroke prevention) Drug
Intervention Desc: Antiplatelet agent; inhibits thromboxane A2
- Clopidogrel (Plavix®)Drug
Other Names: PLAVIX(R) Intervention Desc: Participants will receive aspirin + clopidogrel, specifically: aspirin (325 mg) with clopidogrel (75 mg)-- Participants will take 1 of each pill a day until the end of the study. ARM 1: Kind: Experimental Label: Antiplatelet Description: Participants receive aspirin + placebo OR aspirin + clopidogrel
- Antihypertensives Drug
Intervention Desc: This category includes all BP lowering drugs in stroke prevention trials
- Aspirin Drug
Intervention Desc: Participants receive aspirin + placebo, specifically: aspirin (325 mg) with placebo (an inactive substance). Participants will take 1 of each pill a day until the end of the study. ARM 1: Kind: Experimental Label: Antiplatelet Description: Participants receive aspirin + placebo OR aspirin + clopidogrel
- Placebo Drug
Other Names: Negative control Intervention Desc: an inactive substance ARM 1: Kind: Experimental Label: Antiplatelet Description: Participants receive aspirin + placebo OR aspirin + clopidogrel
- Target of Blood Pressure Other
Intervention Desc: Participants will be assigned to one of 2 groups of blood pressure control. The difference between the two groups is the target level of systolic blood pressure—either 130-149 mmHg or below 130 mmHg; to do so, the scientists will use medications that are already in the market for blood pressure management. ARM 1: Kind: Experimental Label: Blood pressure Description: The goal of the blood pressure aspect of this trial is to find out if lowering blood pressure after stroke helps to prevent recurrent stroke and preserves cognition.
- Allocation: Randomized
- Masking: Double Blind (Subject, Investigator)
- Purpose: Treatment
- Intervention: Parallel Assignment
All eligible patients will be randomized in a double-blind fashion to receive either aspirin 325 mg/day or a combination of aspirin 325 mg/day and clopidogrel 75 mg/day. Hypertensive S3 patients will be randomized to receive antihypertensive therapy with a target systolic blood pressure of either < 150 mmHg or < 130 mmHg.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Recurrent stroke, major vascular events, cognitive decline.|
|Secondary||Intracranial hemorrhage, systemic bleeds, side effects of aggressive antihypertensive therapy, stroke-specific quality of life.|
|Primary||Evidence of clinically defined ischemic stroke (focal neurological deficits persisting for more than 24 hours) confirmed by non-investigational CT or MRI||Mean follow up of 4 years||Yes|
|Primary||Evidence of hemorrhagic stroke; a neurologic deficit associated with intraparenchymal or subarachnoid space lesion on CT/MRI or cerebral hemorrhage demonstrated by surgery or autopsy.||within mean follow-up of 4 years||Yes|
|Secondary||The difference in the rate of cognitive decline among SPS3 participants assigned to receive aspirin alone versus combination of aspirin and clopidogrel, assessed through repeated neuropsychological tests; and major vascular events.||within mean follow-up of 4 years||No|