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Secondary Prevention of Small Subcortical Strokes Trial (SPS3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00059306
Recruitment Status : Completed
First Posted : April 24, 2003
Last Update Posted : April 4, 2013
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
University of British Columbia

Tracking Information
First Submitted Date  ICMJE April 23, 2003
First Posted Date  ICMJE April 24, 2003
Last Update Posted Date April 4, 2013
Study Start Date  ICMJE February 2003
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 23, 2010)
  • 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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2010)
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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Secondary Prevention of Small Subcortical Strokes Trial
Official Title  ICMJE Secondary Prevention of Small Subcortical Strokes (SPS3) Trial
Brief Summary

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.

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 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Cerebrovascular Accident
  • Hypertension
Intervention  ICMJE
  • 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: 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.
  • Other: placebo
    an inactive substance
Study Arms  ICMJE
  • Active Comparator: Antiplatelet
    Participants receive aspirin + placebo OR aspirin + clopidogrel
    Interventions:
    • Drug: aspirin
    • Drug: clopidogrel
    • Other: placebo
  • 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.
    Intervention: Other: Target of Blood Pressure
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2013)
3020
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
2500
Actual Study Completion Date  ICMJE April 2012
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Chile,   Ecuador,   Mexico,   Peru,   Spain,   United States
Removed Location Countries Argentina
 
Administrative Information
NCT Number  ICMJE NCT00059306
Other Study ID Numbers  ICMJE H09-03016
CRC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of British Columbia
Study Sponsor  ICMJE University of British Columbia
Collaborators  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator: Oscar Benavente, M.D. University of British Columbia
Principal Investigator: Robert Hart, M.D. McMaster University
PRS Account University of British Columbia
Verification Date April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP