Clinical trial NCT02014896: Ischemia Care Biomarkers of Acute Stroke Etiology (BASE)
Official title: Ischemia Care Biomarkers of Acute Stroke Etiology (BASE)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ischemic Stroke
Atrial Fibrillation
Transient Ischemic Attacks
Transient Cerebrovascular Events
Thrombotic Stroke
Stroke of Basilar Artery
Cardioembolic Stroke
Keywords: Ischemic Stroke
Transient Ischemic Attack
Transient Neurological Event
Atrial Fibrillation
Cryptogenic Stroke
Gene Expression
RNA
Anticoagulant
NOAC
Antiplatelet
Cardiac monitoring
Point of Care
tPA
Atheroembolic
Lead sponsor: Ischemia Care LLC
Sponsor class: INDUSTRY
First posted: 2013-12-18
Enrollment: 1750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects eligible for enrollment include:

1. Ischemic stroke within 24 hours of symptom onset.
2. Transient Ischemic Attack (TIA) within 24 hours of symptom onset.
3. Non-ischemic transient neurologic event (TNE) within 24 hours of onset.
4. Normal controls that will be non-neurologic patients who are matched with the other ischemic stroke and TIA patients for age, race, gender and smoking plus one or more of the following vascular risk factors: diabetes, hypertension, atrial fibrillation, hyperlipidemia.

Brief summary: The proposed study will validate the clinical use of new biomarker blood tests to identify blood components that may differentiate between diverse stroke etiologies and clinical outcomes as listed below:

1. Differentiate between cardioembolic and large artery atherosclerotic ischemic strokes, when hemorrhagic stroke is ruled out.
2. In cases of ischemic strokes of unknown or "cryptogenic" etiology, determine the ability of biomarker blood tests to predict etiology between cardioembolic and large artery atherosclerotic.
3. In cases of cardioembolic ischemic stroke, further differentiation of cardioembolic ischemic strokes into those caused by atrial fibrillation (AF) and those not caused by AF.
4. Differentiate "transient ischemic attacks" (TIAs) from acute ischemic strokes.
5. Differentiate TIAs from non-ischemic "transient neurological events" (TNE) with similar symptoms.

Detailed description: Acute ischemic stroke (AIS) is a leading cause of adult mortality and morbidity in the United States, affecting over 800,000 individuals, annually, leaving many with permanent disability. Furthermore, hundreds of thousands of Americans experience a transient ischemic attack (TIA), a momentary episode of neurologic dysfunction, which often precedes a major stroke and serves as a warning for future ischemic events. Despite symptoms resolving, experiencing a TIA increases the risk of stroke by 20% within 90 days. Emergent evaluation, prompt acute treatment, and identification of stroke etiology for secondary prevention are key to decreasing the morbidity and mortality associated with cerebrovascular disease. Key to treatment and prevention is the identification of stroke etiology - large vessel atherosclerosis, cardioembolic phenomenon, or in-situ small vessel cerebrovascular disease - since primary and secondary prevention measures differ based on stroke subtype. The diagnosis of ischemic stroke includes a combination of patient history, clinical assessment, and brain imaging. However, identifying the cause of cerebrovascular ischemia is challenging and routinely assigned of cryptogenic origin.

Therefore, there is a great need to understand the pathogenesis of TIA and AIS events in order to develop more effective preventative measures. Recent studies have identified the differential expression of genes in whole blood that may differentiate the major ischemic stroke types. Such differences may help identify TIA and AIS events that are more likely to respond to therapy specifically tailored to the major stroke type. Furthermore, by establishing a more robust standard for secondary prevention, future stroke events may be avoided.

BASE is a multisite prospective study with a estimated enrollment of up to 1100 subjects adult subjects and 100 age, gender and co-morbidity matched controls ("Controls") will be recruited from patients who present to the Emergency Department (ED) or hospital with suspected AIS or TIA. Research personnel will identify potential patients by responding to "Brain Attacks" pages from the ED to the Stroke Team for patients who meet current Brain Attack criteria. Following evaluation by the ED and neurology physicians, the clinical coordinator will verify the patient had a suspected AIS or TIA and meets eligibility criteria. The patient or their legal surrogate will be approached for study participation. Written informed consent will be obtained for all subjects enrolled.

There are two recruitment windows related to BASE determined by time of symptom onset, time of presentation at ED or hospital, and ability to consent:

1. "BASE" - patients that present with suspected stroke symptoms within 18 hours of symptom onset or last known normal time OR
2. "BASE 24" - patients that present within 24 hours +/- 6 hours (i.e. 18 - 30 hour window) of symptom onset or last known normal time and clinical evidence suggesting Acute Ischemic Stroke.

Eligibility criteria: Inclusion Criteria:

* Patients \>18 years of age
* Signs and symptoms suggestive of AIS or TIA
* One of the following:

  1. BASE - Arrival to the emergency department or hospital within 18 hrs of symptom onset or last known normal time
  2. BASE 24 - Arrival to the emergency department or hospital within 24 hours +/- 6 hours (i.e. 18 - 30 hour window) of symptom onset or last known normal time and clinical evidence suggesting Acute Ischemic Stroke.
* Head CT or MRI ruling out other pathology such as vascular malformation, hemorrhage, tumor or abscess which would likely be responsible for presenting neurologic symptoms
* Informed consent obtained

Exclusion Criteria:

* Any central nervous system infection, i.e. meningitis or encephalitis in the past 30 days
* Any form of head trauma, stroke or intracranial hemorrhage in the past 30 days
* Known primary or metastatic cancer involving the brain
* Active Cancer defined as a diagnosis of cancer, within 6 months before enrollment, any treatment for cancer within the previous 6 months, or recurrent or metastatic cancer.
* Autoimmune diseases: such as lupus, rheumatoid arthritis, Crohn's disease, ulcerative colitis
* Active infectious diseases (eg. HIV/AIDS, hepatitis C)
* Any underlying medical condition which in the opinion of the investigator would prohibit the patient from providing informed consent
* Major surgery within three months prior to the index event

Primary outcomes:
measure: Cardioembolic and large vessel stroke stiology
timeFrame: Up to 60 days.
measure: TIA differentiation from non ischemic events (TNE).
timeFrame: Up to 60 days.
Secondary outcomes:
measure: Cryptogenic stroke
timeFrame: Up to 60 days.
measure: Atrial fibrillation and stroke
timeFrame: Up to 60 days.
measure: Stroke and TIA, differentiation
timeFrame: Up to 60 days.
Other outcomes:
measure: Development of point of care testing for ischemic stroke, transient ischemic attack (TIA), and transient neurological events (TNE).
timeFrame: Up to 60 days.
Locations:
city: Sacramento
country: United States
facility: Dignity Health Mercury San Juan
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital (UCSF)
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center Hospital
state: California
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Beaumont Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University, University Hospital in St Louis
state: Missouri
city: Livingston
country: United States
facility: The Stroke Center at Saint Barnabas Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center (University Hospital for Albert Einstein College of Medicine)
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Department of Neurology - Stroke Division
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital/ Ohio Health Research Institute
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Zanesville
country: United States
facility: Genesis Healthcare System
state: Ohio
city: Portland
country: United States
facility: Providence Health and Services
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Center for Neurologic Research
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: UT Health Department of Neurology
state: Texas
Study officials:
affiliation: Ischemia Care
name: Frank Peacock, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Edward Jauch, MD
role: PRINCIPAL_INVESTIGATOR
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