Secondary Prevention of Small Subcortical Strokes Trial (SPS3)
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| ClinicalTrials.gov Identifier: NCT00059306 |
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Recruitment Status :
Completed
First Posted : April 24, 2003
Last Update Posted : April 4, 2013
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cerebrovascular Accident Hypertension | Drug: aspirin Drug: clopidogrel Other: Target of Blood Pressure Other: placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 3020 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Secondary Prevention of Small Subcortical Strokes (SPS3) Trial |
| Study Start Date : | February 2003 |
| Actual Primary Completion Date : | April 2012 |
| Actual Study Completion Date : | April 2012 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Antiplatelet
Participants receive aspirin + placebo OR aspirin + clopidogrel
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Drug: aspirin
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. Drug: clopidogrel 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. Other: placebo an inactive substance |
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Active Comparator: Blood pressure
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.
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Other: Target of Blood Pressure
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. |
- Evidence of clinically defined ischemic stroke (focal neurological deficits persisting for more than 24 hours) confirmed by non-investigational CT or MRI [ Time Frame: Mean follow up of 4 years ]
- 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. [ Time Frame: within mean follow-up of 4 years ]
- 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. [ Time Frame: within mean follow-up of 4 years ]
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| Ages Eligible for Study: | 30 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
INCLUSION:
Small subcortical ischemic stroke or subcortical TIA.
Inclusion criteria are based on TOAST criteria supplemented by required MRI data. All of the following criteria must be met:
- One of the lacunar stroke clinical syndromes (adapted from Fisher) lasting > 24 hrs within the past 6 months
- Absence of signs or symptoms of cortical dysfunction such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect, etc.
- No ipsilateral cervical carotid stenosis (≥50%) by a reliable imaging modality done in an approved laboratory since the qualifying small subcortical stroke (S3), if hemispheric.
- No major-risk cardioembolic sources requiring anticoagulation or other specific therapy. Minor-risk cardioembolic sources will be permitted if anticoagulation is not prescribed by the patient's primary care physician.
- Subcortical TIA with corresponding lesion on DWI.
- MRI evidence of S3: a. Presence of an S3 (1.5 and 2 cm in diameter corresponding to the qualifying event on DWI; when TIA, ADC image must confirm lesion or T2/FLAIR (hyperintense lesions) (required for all brainstem events) OR multiple S3s on FLAIR/TI(<1.5 cm in diameter) (hypointense lesions) b. Absence of cortical stroke and large subcortical stroke (recent or remote).
EXCLUSION:
To be eligible for entry into the study, the patient must not meet any of the criteria listed below:
- Disabling stroke (Modified Rankin Scale less than or equal to 4)
- Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke
- Age under 30 years
- High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc)
- Anticipated requirement for long-term use of anticoagulants (e.g. recurrent DVT) or other antiplatelets
- Prior cortical stroke (diagnosed either clinically or by neuroimaging), or prior cortical or retinal TIA
- Prior ipsilateral carotid endarterectomy
- Impaired renal function: GFR <40
- Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR)
- A score < 24 (adjusted for age and education) on the Folstein Mini Mental Status Examination
- Medical contraindication to MRI
- Pregnancy or women of child-bearing potential who are not following an effective method of contraception
- Geographic or social factors making study participation impractical
- Unable or unwilling to provide informed consent
- Unlikely to be compliant with therapy/unwilling to return for frequent clinic visits
- Patients concurrently participating in another study with an investigational drug or device
- Other likely specific cause of stroke (e.g. dissection, vasculitis, prothrombotic diathesis, drug abuse)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00059306
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| Principal Investigator: | Oscar Benavente, M.D. | University of British Columbia | |
| Principal Investigator: | Robert Hart, M.D. | McMaster University |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | University of British Columbia |
| ClinicalTrials.gov Identifier: | NCT00059306 |
| Other Study ID Numbers: |
H09-03016 CRC |
| First Posted: | April 24, 2003 Key Record Dates |
| Last Update Posted: | April 4, 2013 |
| Last Verified: | April 2013 |
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stroke hypertension high blood pressure lacunar stroke |
subcortical stroke aspirin clopidogrel |
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Stroke Hypertension Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Aspirin Clopidogrel Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Platelet Aggregation Inhibitors Cyclooxygenase Inhibitors Enzyme Inhibitors Antipyretics Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents |