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Secondary Prevention of Small Subcortical Strokes Trial (SPS3)
This study is currently recruiting participants.
Verified by National Institute of Neurological Disorders and Stroke (NINDS), November 2008
Sponsors and Collaborators: University of Texas
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT00059306
  Purpose

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.


Condition Intervention Phase
Cerebrovascular Accident
Hypertension
Drug: aspirin
Drug: clopidogrel
Other: Target of Blood Pressure
Other: placebo
Phase III

MedlinePlus related topics: High Blood Pressure
Drug Information available for: Acetylsalicylic acid Clopidogrel Clopidogrel Bisulfate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment
Official Title: Secondary Prevention of Small Subcortical Strokes (SPS3) Trial

Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):

Primary Outcome Measures:
  • 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 3 years ] [ Designated as safety issue: Yes ]
  • 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 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The difference in the rate of cognitive decline among SPS3 participants assigned to received aspirin alone versus combination of aspirin and clopidogrel, assessed through repeated neuropsychological tests. [ Time Frame: within mean follow-up of 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 2500
Study Start Date: February 2003
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Antiplatelet: Active Comparator
Participants receive aspirin + placebo OR aspirin + clopidogrel
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
Blood pressure: Active Comparator
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.
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.

Detailed Description:

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 2500 participants (20 percent of whom will be Hispanic Americans) 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.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION:

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 <4)
  • Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke
  • Age under 40 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00059306

Contacts
Contact: Oscar Benavente, M.D. (210) 592-0404 benavente@uthscasa.edu

  Show 63 Study Locations
Sponsors and Collaborators
University of Texas
Investigators
Principal Investigator: Oscar Benavente, M.D. University of Texas
Principal Investigator: Robert Hart, M.D. University of Texas
  More Information

Additional Information:
No publications provided

Responsible Party: University of Texas Health Science Center at San Antonio, School of Medicine ( Oscar Benavente, MD, Associate Professor and SPS3 Principal Investigator )
Study ID Numbers: R01NS38529, CRC
Study First Received: April 23, 2003
Last Updated: November 13, 2008
ClinicalTrials.gov Identifier: NCT00059306  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):
stroke
hypertension
high blood pressure
lacunar stroke
subcortical stroke
aspirin
clopidogrel

Study placed in the following topic categories:
Cerebral Infarction
Stroke
Vascular Diseases
Central Nervous System Diseases
Ischemia
Brain Diseases
Cerebrovascular Disorders
Aspirin
Clopidogrel
Neoplasm Metastasis
Brain Ischemia
Brain Infarction
Infarction
Hypertension

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Hematologic Agents
Nervous System Diseases
Physiological Effects of Drugs
Enzyme Inhibitors
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions
Fibrin Modulating Agents
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 12, 2009