Levels of Inflammatory Markers in the Treatment of Stroke-An SPS3 Ancillary Study
- Conditions
- StrokeHypertension
- Registration Number
- NCT00579306
- Lead Sponsor
- Columbia University
- Brief Summary
The goals of this trial are to determine the prognostic significance of an elevated level of inflammatory blood markers in people who have experienced small subcortical strokes and who are enrolled in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.
- Detailed Description
Inflammation is increasingly recognized as playing a central role in atherosclerosis and coronary artery disease. And, peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these risk markers-which have the potential to be modified-to prognosis after ischemic stroke is less clear.
The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) study will address questions about the role of inflammatory markers in secondary stroke prevention in a cost-effective manner using the well-established framework of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. The SPS3 trial is an ongoing Phase 3, multicenter secondary stroke prevention trial that focuses on preventing stroke recurrence in people with small vessel ischemic stroke, or lacunes.
The overall purpose of the LIMITS study is to determine if serum levels of inflammatory markers-such as hsCRP, serum amyloid A (SAA), CD40 ligand (CD40L), and monocyte chemoattractant protein-1 (MCP-1)-predict recurrent stroke and other vascular events among people with a history of small artery ischemic stroke. The project will also determine if these markers predict which people will respond best to dual antiplatelet therapy with clopidogrel and aspirin.
The specific aims of LIMITS are to determine if hsCRP, SAA, CD40L, and MCP-1 levels are independent risk factors for recurrent ischemic stroke, and for recurrent ischemic stroke, myocardial infarction, and death in participants in the SPS3 trial after adjusting for demographic and traditional stroke risk factors, and other treatments, using a prospective cohort of people with small subcortical strokes from the SPS3 trial. LIMITS also aims to compare the efficacy of dual versus single antiplatelet therapy among participant groups with and without elevated baseline inflammatory marker levels for the outcome of a.) recurrent stroke, and b.) recurrent ischemic stroke, myocardial infarction, or death.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1244
- Patient must be randomized within 6 months of qualifying small subcortical stroke (S3) or subcortical TIA
- One of the following lacunar syndromes: PMH; pure sensory stroke; sensorimotor stroke; ataxic hemiparesis; dysarthria; hemiballism; PMH with facial sparing, horizontal gaze palsy, contralateral III palsy, contralateral VI palsy; Ataxia with contralateral III palsy; pure dysarthria
- Absence of cortical dysfunction (aphasia, apraxia, agnosia)
- No ipsilateral cervical carotid stenosis (>= 50%) if S3 is hemispheric
- No major-risk cardioembolic sources requiring anti-coagulation
- MRI evidence of S3 that is >=2.0 cm in diameter if DWI/bright lesion on FLAIR/T2 or <=1.5cm hypointense lesion on FLAIR/T1, corresponding to the qualifying event (required for all brainstem events) OR multiple S3 in cerebral hemispheres of <=1.5cm hypointense lesions on FLAIR/T1 AND absence of cortical stroke and large subcortical stroke.
- Disabling stroke (Ranking Scale >= 4)
- Prior hemorrhagic stroke
- Age <30 years
- High risk of bleeding (recurrent GI or GU bleeding, active peptic ulcer disease, etc)
- Need for long-term use of anticoagulants or other antiplatelet agents.
- Prior cortical or retinal stroke / TIA
- Prior ipsilateral carotid endarterectomy if hemispheric S3
- Impaired renal function: GFR<40 cc/min
- Intolerance/contraindication to aspirin or clopidogrel
- Adjusted Folstein MMSE <24
- Medical contraindication to MRI
- Pregnancy or child-bearing potential without contraception
- Other specific causes of stroke (e.g. dissection, vasculitis, drug abuse)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Percentage of participants with recurrent stroke Up to 5 years Participants with recurrence of any stroke during follow-up, including ischemic (an acute localized ischemic lesion in the brain not attributable to central nervous system infection, tumor, demyelinating, or degenerative neurologic diseases due to an occlusive vascular disorder) and hemorrhagic (acute extravasation of blood into the parenchyma of the central nervous system or subarachnoid space).
- Secondary Outcome Measures
Name Time Method Percentage of participants developing major cognitive decline Up to 5 years Documentation of a major cognitive decline during follow-up. This is a clinical decline in cognitive function manifested by functional deterioration/behavioral changes that are not associated with a clinical stroke event.
Criteria: Both A and B must be met:
A) A drop in the Cognitive Abilities Screening Instrument (CASI) score of \> 10 points since study entry and sustained on repeat testing in approximately one month B) Associated behavioral changes and/or function
Trial Locations
- Locations (45)
University of Miami
🇺🇸Miami, Florida, United States
University Hospitals of Cleveland, Case Western Reserve University,Case Western Neurological Unit, 11100 Euclid Avenue, Lakeside 5508
🇺🇸Cleveland, Ohio, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
University of Texas South Western Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Sutter Neuroscience Institute
🇺🇸Sacramento, California, United States
University of South Alabama
🇺🇸Mobile, Alabama, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Wake Forest University Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Melbourne Internal Medicine Associates
🇺🇸Melbourne, Florida, United States
University of California, San Diego Medical Center
🇺🇸La Jolla, California, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Mercy Medical Center
🇺🇸Des Moines, Iowa, United States
Hospital Clinico Universitario de Santiago de Compostela
🇪🇸Barcelona, Spain
Hospital Nacional Alberto Sabogal
🇵🇪Lima, Peru
Marshfield Clinic Research Foundation
🇺🇸Marshfield, Wisconsin, United States
University of Arizona Collage of Medicine
🇺🇸Tucson, Arizona, United States
Hospital Germans Trias i Pujol,
🇪🇸Barcelona, Spain
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
St. Louis University
🇺🇸Saint Louis, Missouri, United States
Helen Hayes Hospital
🇺🇸West Haverstraw, New York, United States
Cooper University Hospital,
🇺🇸Camden, New Jersey, United States
Rochester General Hospital
🇺🇸Rochester, New York, United States
Pontificia Universidad Catolica de Chile
🇨🇱Santiago, Chile
St. John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
Hospital-Clinica Kennedy
🇪🇨Guayaquil, Ecuador
Instituto Nacional de Neurología y Neurocirugía
🇲🇽Mexico, Mexico City, Mexico
Dalhousie University Center for Clinical Research
🇨🇦Halifax, Nova Scotia, Canada
Universidad Autonoma de Guadalajara
🇲🇽Guadalajara, JAL, Mexico
Hospital del Sagrat Cor
🇪🇸Barcelona, Spain
Hospital Charles LeMoyne Centre de recherché
🇨🇦Greenfield Park, Quebec, Canada
Hospital Naval Almirante Nef
🇨🇱Viña del Mar, Chile
Metro Health Medical Center
🇺🇸Cleveland, Ohio, United States
Hospital Universitario de Bellvitge, Spain
🇪🇸Barcelona, Spain
McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Dr. Josep Trueta
🇪🇸Barcelona, Spain
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Wayne State University
🇺🇸Detroit, Michigan, United States