Secondary Prevention of Small Subcortical Strokes Trial - Full Text View

Sponsor:	The University of Texas Health Science Center at San Antonio
Collaborator:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	The University of Texas Health Science Center at San Antonio
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

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Secondary Prevention of Small Subcortical Strokes (SPS3) Trial

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Acetylsalicylic acid Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Further study details as provided by The University of Texas Health Science Center at San Antonio:

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.

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

The University of Texas Health Science Center at San Antonio

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:	Oscar Benavente, M.D.	University of Texas
Principal Investigator:	Robert Hart, M.D.	University of Texas

More Information

Additional Information:

study website This link exits the ClinicalTrials.gov site

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:	July 23, 2009
ClinicalTrials.gov Identifier:	NCT00059306 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by The University of Texas Health Science Center at San Antonio:

stroke
hypertension
high blood pressure
lacunar stroke

subcortical stroke
aspirin
clopidogrel

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Cerebral Infarction
Hematologic Agents
Physiological Effects of Drugs
Fibrinolytic Agents
Brain Diseases
Cerebrovascular Disorders
Fibrin Modulating Agents
Aspirin
Sensory System Agents
Therapeutic Uses
Brain Ischemia
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal

Analgesics
Cyclooxygenase Inhibitors
Nervous System Diseases
Stroke
Vascular Diseases
Central Nervous System Diseases
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions
Analgesics, Non-Narcotic
Clopidogrel
Platelet Aggregation Inhibitors
Brain Infarction
Peripheral Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on March 18, 2010