Clinical trial NCT00579306: Levels of Inflammatory Markers in the Treatment of Stroke-An SPS3 Ancillary Study
Official title: Levels of Inflammatory Markers in the Treatment of Stroke
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypertension
Stroke
Keywords: hypertension
stroke
cerebrovascular accident
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2007-12-24
Enrollment: 1244
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a symptomatic small vessel stroke within prior 6 month and enrolled in SPS3

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Percentage of participants with recurrent stroke
timeFrame: Up to 5 years
Secondary outcomes:
measure: Percentage of participants developing major cognitive decline
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Collage of Medicine
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter Neuroscience Institute
state: California
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Des Moines
country: United States
facility: Mercy Medical Center
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: St. John's Mercy Medical Center
state: Missouri
city: Camden
country: United States
facility: Cooper University Hospital,
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: West Haverstraw
country: United States
facility: Helen Hayes Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland, Case Western Reserve University,Case Western Neurological Unit, 11100 Euclid Avenue, Lakeside 5508
state: Ohio
city: Cleveland
country: United States
facility: Metro Health Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Dallas
country: United States
facility: University of Texas South Western Medical Center
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Marshfield
country: United States
facility: Marshfield Clinic Research Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Halifax
country: Canada
facility: Dalhousie University Center for Clinical Research
state: Nova Scotia
city: Greenfield Park
country: Canada
facility: Hospital Charles LeMoyne Centre de recherché
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile
city: Viña del Mar
country: Chile
facility: Hospital Naval Almirante Nef
city: Guayaquil
country: Ecuador
facility: Hospital-Clinica Kennedy
city: Guadalajara
country: Mexico
facility: Universidad Autonoma de Guadalajara
state: JAL
city: Mexico
country: Mexico
facility: Instituto Nacional de Neurología y Neurocirugía
state: Mexico City
city: Lima
country: Peru
facility: Hospital Nacional Alberto Sabogal
city: Barcelona
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital del Sagrat Cor
city: Barcelona
country: Spain
facility: Hospital Dr. Josep Trueta
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol,
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge, Spain
Study officials:
affiliation: Columbia University
name: Mitchell S. Elkind, MD, MS, FAAN
role: PRINCIPAL_INVESTIGATOR
affiliation: UTHSC San Antonio (SPS3 Principal Investigator)
name: Oscar Benavente, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UTHSC San Antonio (SPS3 Principal Investigator)
name: Robert Hart, MD
role: PRINCIPAL_INVESTIGATOR
References: