Secondary Prevention of Small Subcortical Strokes Trial (SPS3)

April 2, 2013 updated by: University of British Columbia

Secondary Prevention of Small Subcortical Strokes (SPS3) Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

3020

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Calgary Health
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 2B5
        • SPS3 Coordinating Center
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 4V7
        • Halifax
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital General Campus
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Greenfield Park
      • Montreal, Quebec, Canada, H37 1E2
        • McGill-Jewish General
      • Montreal, Quebec, Canada, H3G 1A4
        • McGill-Montreal General
      • Quebec City, Quebec, Canada, G1J 1Z4
        • CHA-Hospital de L'Enfant-Jesus
  • Chile
      • Santiago, Chile
        • Hospital Clinico de la Universidad Católica de Chile
      • Viña del Mar, Chile, 2530116
        • Hospital Naval Almirante Nef, 'Subida Alessandri s/n, Hall A, Oficina 9
  • Ecuador
      • Guayaquil, Ecuador
        • Hospital-Clinica Kennedy
  • Mexico
      • Guadalajara, Mexico, 44280
        • Antiguo Hospital Civil de Guadalajara
      • Mexico City, Mexico, 14000
        • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zuibrán
      • Mexico City, Mexico, 14269
        • Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 644460
        • Hospital de La Universidad Autonoma de Nuevo Leon
  • Peru
    • Lima
      • Bellavista-Callao, Lima, Peru
        • Hospital Sabogal Essalud-Unidad de Investigacion
  • Spain
      • Badalona, Spain, 08916
        • Hosp. Universitario Germans Trias I Pujol
      • Barcelona, Spain, 08003
        • Hospital del Mar, Passeig Marítim 25-29
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu I Sant Pau, c/Sant Antoni Maria Claret, 167
      • Barcelona, Spain, 08029
        • Hospital del Sagrat Cor. Quinta de Salut I'Alianca, c/Viladomat 288
      • Barcelona, Spain, 08208
        • Hosp. Parc Tauli de Sabadell
      • Girona, Spain, 17007
        • Hosp. de Girona Dr. Josep Trueta
      • Madrid, Spain, 28046
        • Hospital La Paz
      • Santiago de Compostela, Spain, 15782
        • Universidad de Santiago de Compostela, Facultad de Medicina y Odontologia
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36617
        • University of Southern Alabama Stroke Center
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Catholic Healthcare West
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Scottsdale
      • Tucson, Arizona, United States, 85724
        • University of Arizona, Department of Neurology
    • California
      • San Diego, California, United States, 92103-8466
        • University of California San Diego Medical Center
      • San Francisco-Fresno, California, United States
        • University of California San Francisco-Fresno
    • Colorado
      • Englewood, Colorado, United States
        • Denver
    • Florida
      • Melbourne, Florida, United States
        • Melbourne
      • Miami, Florida, United States, 33136
        • Miami-University of Miami, Miller School of Medicine
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Emory University, Grady Health System
    • Iowa
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center-Ruan Neurology Clinical Research
    • Kentucky
      • Lexington, Kentucky, United States, 40506-0230
        • University of Kentucky, Aging/Stroke Program
    • Maryland
      • Bethesda, Maryland, United States
        • Suburban Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital, Department of Neurology
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Berman Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Stroke Center KA-SL-13
    • Missouri
      • Sant Louis, Missouri, United States
        • University of Washington
      • St. Louis, Missouri, United States, 63110
        • Tenet Health, St. Louis University
      • St. Louis, Missouri, United States, 63141
        • St. John's Mercy
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper University Hospital
    • New York
      • Buffalo, New York, United States
        • Buffalo
      • Haverstraw, New York, United States, 10993
        • Helen Hayes Hospital
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Rochester, New York, United States, 14621
        • Rochester General Hospital
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1078
        • Wake Forest University, Sciences-Neurology
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Cleveland, Ohio, United States, 44106
        • Case Western
      • Columbus, Ohio, United States, 43210
        • Ohio State University, Division of Stroke
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390-8897
        • University of Texas Southwestern
      • Houston, Texas, United States, 77030
        • Scurlock Stroke Center
      • San Antonio, Texas, United States, 78229-3900
        • University of Texas Health Science Center
    • Washington
      • Seattle, Washington, United States, 98104-2499
        • University of Washington
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic, Department of Neurology
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin-Neurology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Antiplatelet
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
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
within mean follow-up of 4 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
within mean follow-up of 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Oscar Benavente, M.D., University of British Columbia
  • Principal Investigator: Robert Hart, M.D., McMaster University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2003

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

April 23, 2003

First Submitted That Met QC Criteria

April 23, 2003

First Posted (Estimate)

April 24, 2003

Study Record Updates

Last Update Posted (Estimate)

April 4, 2013

Last Update Submitted That Met QC Criteria

April 2, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H09-03016
  • CRC (NINDS)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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