Secondary Prevention of Small Subcortical Strokes Trial (SPS3)

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)