The Intravascular Cooling in the Treatment of Stroke 2/3 Trial

Phase 2

Terminated

Conditions: Stroke, Acute

Interventions: Device: hypothermia and anti-shivering treatment

Registration Number: NCT01123161

Lead Sponsor: University of California, San Diego

Brief Summary: The purpose of this trial is to determine whether the combination of thrombolysis and hypothermia is superior to thrombolysis alone for the treatment of acute ischemic stroke.

Detailed Description: A stroke is usually caused by a blockage in one of the arteries that carries blood to the brain. Research has shown that tissue plasminogen activator (tPA)-a naturally occurring protein that opens blocked arteries by dissolving blood clots - activates the body's ability to dissolve recently formed blood clots and reduces or prevents the brain damage caused by a stroke.

The Food and Drug Administration (FDA) has approved the use of tPA for people having a stroke when taken within 3 hours of stroke onset.

Researchers believe that a lower body temperature (hypothermia) may be beneficial while a stroke is happening because hypothermia may prevent further brain injury, or may make the stroke less damaging.

Patients will receive a standard stroke evaluation, which includes blood tests, a computed tomography (CT) scan, complete physical and neurological examinations, and an electrocardiogram (EKG) to determine eligibility for the study.

There are two study groups - tPA alone or tPA with cooling (hypothermia). Participants will be randomly assigned to one of the two study groups. Length of participation (including observation after the patient leaves the hospital) is 90 days.

This study is part of the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS), which allows researchers to enhance and initiate translational research that ultimately will benefit stroke patients by treating more patients in less than 2 hours, and finding ways to treat additional patients later.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 120

Inclusion Criteria

Age 22 to 82 years old inclusive
Patient receiving IV rt-PA using standard guidelines
NIHSS score ≥ 7 and ≤ 20 (right hemisphere) or ≥ 7 and ≤ 24 (left hemisphere) at the time of randomization
Pre-stroke mRS 0-1
Able to begin endovascular phase of hypothermia within 2 hours of tPA completion
Written Informed Consent, signed and dated by the patient (or patient's authorized representative)

Exclusion Criteria

Etiology other than ischemic stroke
Item 1a on NIHSS > 1 at the time of randomization
Clinical symptoms consistent with brainstem or cerebellar stroke
Classic lacunar syndrome with imaging confirmation of small deep ischemia, but randomization will not be delayed for neuroimaging other than initial scan to exclude hemorrhage
Known contraindications to hypothermia, such as known hematologic dyscrasias that affect thrombosis (cryoglobulinemia, Sickle cell disease, serum cold agglutinins), or vasospastic disorders such as Raynaud's or thromboangiitis obliterans
Known co-morbid conditions that are likely to complicate therapy in the opinion of the investigator, e.g., i. Heart failure (NYHA class III and IV)* ii. Uncompensated arrhythmia iii. Severe Liver disease iv. History of pelvic or abdominal mass likely to compress inferior vena cava v. IVC filters vi. HIV positive vii. Clinically active hypo or hyperthyroidism viii. Renal insufficiency likely to impair meperidine clearance ix. Chronic ethanol abuse x. History of HIT (heparin induced thrombocytopenia)
Pregnancy (All women of child-bearing potential must have a negative pregnancy test, urine or blood, prior to therapy.)
Medical conditions likely to interfere with patient assessment.
Known allergy to meperidine or buspirone
Currently taking or used within previous 14 days MAO-I class of medication.
Life expectancy < 6 months
Not likely to be available for long-term follow-up
Use, or planned use, of intra-arterial thrombolysis, mechanical clot removal, or other experimental or approved acute therapy for this stroke event
Chest radiograph or clinical presentation suggestive of pneumonia or clinically significant pulmonary edema at baseline.
Temperature upon admission greater than or equal to 38°C

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Group 2 : IV t-PA and hypothermia and anti-shivering treatment	hypothermia and anti-shivering treatment	IV tpa and hypothermia and anti-shivering treatment

Primary Outcome Measures

Name	Time	Method
Incidence of Any Intracranial Hemorrhage (ICH) Within 48 Hours of Stroke Onset	48 hours	Incidence (number) of any intracranial hemorrhage (ICH) (whether or not symptomatic) within 48 hours of stroke onset will be presented by treatment group and overall.
90 Day Mortality	90 days	Mortality prior to the 90-day evaluation.
The Primary Outcome is the Proportion of Patients Achieving a Favorable Outcome Defined as Modified Rankin Scale Score of 0 or 1, Assessed 90 Days After Treatment.	90 days	Modified Rankin describes disability: 0 is free of any disability or symptoms, 6 is death, and higher grades between 0 and 6 reflect progressively greater disability
Incidence of Any Symptomatic Intracranial Hemorrhage (sICH) Within 48 Hours of Stroke Onset	48 hours	Incidence (number) of Symptomatic ICH (sICH) within 48 hours of stroke onset will be presented by treatment group and overall. Patients with neuroworsening (4 or more point increase in NIHSS , or a decline in the NIHSS consciousness item 1A score of more than 1 point, or a motor deterioration lasting more than 8 hours, all not due to iatrogenic cause) and hemorrhage seen on brain images in whom the investigator attributes the clinical change to the hemorrhage.
Incidence of Pneumonia	7 days or discharge whichever comes first	Number subjects diagnosed with pneumonia according to CDC criteria will be presented by treatment group and overall, regardless of seriousness

Secondary Outcome Measures

Name	Time	Method
NIHSS Scores at 90 Days	90 days	The National Institutes of Health Stroke Scale (NIHSS) is used to quantify neurological deficit. The scale ranges from 0 (best) to 42 points (worst). Between scores of 0 to 42, higher values reflect progressively greater deficit.
The Barthel Index Measure of Activities of Daily Living;	90 days	The Barthel index measures independence in activities of daily living from 0 (worst) to 100 (best) in 5 point increments. Higher scores between 0 and 100 reflect progressively greater levels of independence. Scores were dichotomized at 90 so that a score of 95 or 100 was considered a successful treatment.

Trial Locations

Locations (31): Hoag Memorial Hospital Presbyterian
🇺🇸
Newport Beach, California, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
UT Southwestern
🇺🇸
Dallas, Texas, United States
University of Texas Health Science Center
🇺🇸
Houston, Texas, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Gulf Coast Medical Center
🇺🇸
Fort Myers, Florida, United States
St. Joseph's Hospital
🇺🇸
Tampa, Florida, United States
Intercoastal Medical Group
🇺🇸
Sarasota, Florida, United States
Alexian Brothers Medical Center
🇺🇸
Elk Grove Village, Illinois, United States
Parkview Hospital
🇺🇸
Fort Wayne, Indiana, United States
Michigan State University
🇺🇸
East Lansing, Michigan, United States
Ruan Neurology Clinic and Research Center
🇺🇸
Des Moines, Iowa, United States
North Memorial Medical Center
🇺🇸
Robbinsdale, Minnesota, United States
University of Toledo Medical Center
🇺🇸
Toledo, Ohio, United States
Saint Louis University Medical Center
🇺🇸
St. Louis, Missouri, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Lehigh Valley Health Network
🇺🇸
Allentown, Pennsylvania, United States
Seton Medical Center Austin
🇺🇸
Austin, Texas, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Medical University Innsbruck
🇦🇹
Innsbruck, Austria
CHUV
🇨🇭
Lausanne, Switzerland
University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
Scripps Mercy Medical Center
🇺🇸
San Diego, California, United States
University of Alabama Hospital
🇺🇸
Birmingham, Alabama, United States
University of California San Diego Health System
🇺🇸
San Diego, California, United States
University of Miami, Jackson Memorial Hospital
🇺🇸
Miami, Florida, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States