Secondary Prevention of Small Subcortical Strokes Trial

Hypertension Clinical Trial

— SPS3  

Official title:

Secondary Prevention of Small Subcortical Strokes (SPS3) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00059306
• Other study ID #: H09-03016
• Secondary ID: CRC
• Status: Completed
• Phase: Phase 3
• First received: April 23, 2003
• Last updated: April 2, 2013
• Start date: February 2003
• Est. completion date: April 2012

Study information

• Verified date: April 2013
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3020
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebrovascular Accident
• Hypertension
• Stroke

Intervention

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.
• 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.
• placebo
an inactive substance

Locations

Country	Name	City	State
Canada	Calgary Health	Calgary	Alberta
Canada	Greenfield Park	Greenfield Park	Quebec
Canada	Halifax	Halifax	Nova Scotia
Canada	McGill-Jewish General	Montreal	Quebec
Canada	McGill-Montreal General	Montreal	Quebec
Canada	Ottawa Hospital General Campus	Ottawa	Ontario
Canada	CHA-Hospital de l'Enfant-Jesus	Quebec City	Quebec
Canada	SPS3 Coordinating Center	Vancouver	British Columbia
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
Ecuador	Hospital-Clinica Kennedy	Guayaquil
Mexico	Antiguo Hospital Civil de Guadalajara	Guadalajara
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zuibrán	Mexico City
Mexico	Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez	Mexico City
Mexico	Hospital de La Universidad Autonoma de Nuevo Leon	Monterrey	Nuevo Leon
Peru	Hospital Sabogal Essalud-Unidad de Investigacion	Bellavista-Callao	Lima
Spain	Hosp. Universitario Germans Trias I Pujol	Badalona
Spain	Hosp. Parc Tauli de Sabadell	Barcelona
Spain	Hospital de la Santa Creu I Sant Pau, c/Sant Antoni Maria Claret, 167	Barcelona
Spain	Hospital Del Mar, Passeig Marítim 25-29	Barcelona
Spain	Hospital del Sagrat Cor. Quinta de Salut I'Alianca, c/Viladomat 288	Barcelona
Spain	Hosp. de Girona Dr. Josep Trueta	Girona
Spain	Hospital La Paz	Madrid
Spain	Universidad de Santiago de Compostela, Facultad de Medicina y Odontologia	Santiago de Compostela
United States	Emory University, Grady Health System	Atlanta	Georgia
United States	Suburban Hospital	Bethesda	Maryland
United States	Boston University	Boston	Massachusetts
United States	Buffalo	Buffalo	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	Case Western	Cleveland	Ohio
United States	Metrohealth Medical Center	Cleveland	Ohio
United States	Ohio State University, Division of Stroke	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Mercy Medical Center-Ruan Neurology Clinical Research	Des Moines	Iowa
United States	Henry Ford Hospital, Department of Neurology	Detroit	Michigan
United States	Wayne State	Detroit	Michigan
United States	Denver	Englewood	Colorado
United States	Helen Hayes Hospital	Haverstraw	New York
United States	Scurlock Stroke Center	Houston	Texas
United States	University of Kentucky, Aging/Stroke Program	Lexington	Kentucky
United States	Marshfield Clinic, Department of Neurology	Marshfield	Wisconsin
United States	Melbourne	Melbourne	Florida
United States	Miami-University of Miami, Miller School of Medicine	Miami	Florida
United States	Medical College of Wisconsin-Neurology	Milwaukee	Wisconsin
United States	Berman Center	Minneapolis	Minnesota
United States	University of Southern Alabama Stroke Center	Mobile	Alabama
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Catholic Healthcare West	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Stroke Center KA-SL-13	Rochester	Minnesota
United States	Rochester General Hospital	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	University of Texas Health Science Center	San Antonio	Texas
United States	University of California San Diego Medical Center	San Diego	California
United States	University of California San Francisco-Fresno	San Francisco-Fresno	California
United States	University of Washington	Sant Louis	Missouri
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	St. John's Mercy	St. Louis	Missouri
United States	Tenet Health, St. Louis University	St. Louis	Missouri
United States	University of Arizona, Department of Neurology	Tucson	Arizona
United States	Wake Forest University, Sciences-Neurology	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of British Columbia	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Ecuador,  Mexico,  Peru,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evidence of clinically defined ischemic stroke (focal neurological deficits persisting for more than 24 hours) confirmed by non-investigational CT or MRI		Mean follow up of 4 years	Yes
Primary	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.		within mean follow-up of 4 years	Yes
Secondary	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.		within mean follow-up of 4 years	No

External Links

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