Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke
Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke
The purpose of this trial is to evaluate if it is safe to use tissue plasminogen activator
 (tPA) within 6 hours of stroke onset when combined with hypothermia.
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, but not for those who arrive at the hospital more
 than 3 hours after 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. In particular, hypothermia may make it possible to use tPA later than 3
 hours after a stroke begins. This study will determine if it is safe to use tPA within 6
 hours of the start of a stroke when combined with hypothermia.

 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.

 Participants will be randomly assigned to a study group based on when their stroke began.
 Those who arrive at the hospital less than 3 hours from stroke onset will receive tPA alone
 or tPA with cooling (hypothermia). Those who arrive at the hospital 3 to 6 hours after stroke
 onset will be assigned to 1 of 4 groups-receiving either tPA alone, tPA with cooling, cooling
 alone, or standard medical care. 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.
Inclusion Criteria:

 -  Age 18 to 80

 -  All eligibility criteria for t-PA administration for acute ischemic stroke as outlined
 by the NINDS tPA Guidelines are met with the exception of time from onset

 -  Stroke onset within 6 hours prior to planned start of tPA

 -  Any subtype of ischemic stroke with NIHSS < 7 at the time hypothermia begins

 Exclusion Criteria:

 -  Etiology other than ischemic stroke

 -  Item 1a on NIHSS>1 at the time of enrollment

 -  Symptoms resolving or NIHSS < 7 at the time hypothermia begins

 -  Contraindications to hypothermia, such as patients with known hematologic dyscrasias
 which affect thrombosis, (cryoglobulinemia, Sickle cell disease, serum cold
 agglutinins), or vasospastic disorders such as Raynaud's or thromboangiitis
 obliterans.

 -  Known co-morbid conditions likely to complicate therapy, e.g., end-stage
 cardiomyopathy, uncompensated arrhythmia, myopathy, liver disease severe enough to
 elevate bilirubin, history of pelvic or abdominal mass likely to compress inferior
 vena cava, IVC filters, dementia severe enough to prevent valid consent, end-stage
 AIDS, known thyroid deficiency, known renal insufficiency likely to impair meperidine
 (Demerol®) clearance

 -  Intracerebral hematoma

 -  Any intraventricular hemorrhage

 -  SBP > 185 or < 100; DBP > 110 or < 50 mmHg

 -  Pregnancy in women of child-bearing potential (must have pregnancy test, urine or
 blood, prior to therapy).

 -  Medical conditions likely to interfere with patient assessment

 -  Known allergy to meperidine (Demerol®)

 -  Currently taking MAO-I class of medication or used within previous 14 days

 -  Life expectancy < 3 months

 -  Not likely to be available for long-term follow-up.