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Secondary Prevention of Small Subcortical Strokes Trial (SPS3)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT00059306
First received: April 23, 2003
Last updated: April 2, 2013
Last verified: April 2013
  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.

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.


Condition Intervention Phase
Cerebrovascular Accident
Hypertension
Drug: aspirin
Drug: clopidogrel
Other: Target of Blood Pressure
Other: placebo
Phase 3

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:


Further study details as provided by University of British Columbia:

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 4 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 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 3020
Study Start Date: February 2003
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

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

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059306

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

Additional Information:
No publications provided by University of British Columbia

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT00059306     History of Changes
Other Study ID Numbers: H09-03016, CRC
Study First Received: April 23, 2003
Last Updated: April 2, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of British Columbia:
stroke
hypertension
high blood pressure
lacunar stroke
subcortical stroke
aspirin
clopidogrel

Additional relevant MeSH terms:
Cerebral Infarction
Hypertension
Stroke
Brain Diseases
Brain Infarction
Brain Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases
Aspirin
Clopidogrel
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014