Clinical trial NCT00283088: Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke
Official title: Phase 1 Study of Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Stroke
Keywords: stroke
hypothermia
cooling
tissue plasminogen activator
tPA
thrombolysis
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2006-01-27
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.

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, 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and volume of hemorrhage on CT
timeFrame: 48 hours post onset
Secondary outcomes:
measure: Incidence of AE and SAE
timeFrame: 90 days post onset
measure: Mortality in both groups testing whether hypothermia improves mortality after stroke
timeFrame: 90 Day
measure: NIHSS at the end of hypothermia
timeFrame: Hour 23.5 +/- 30 minutes of hypothermia
measure: Modified Rankin and NIHSS
timeFrame: 30 and 90days
measure: CT lesion volume
timeFrame: 30 days
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego, Thornton Hospital
state: California
city: San Diego
country: United States
facility: Scripps Mercy Hospital
state: California
city: San Diego
country: United States
facility: University of California San Diego, Hillcrest Medical Center
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: St. Louis
country: United States
facility: Saint Louis University Medical Center
state: Missouri
city: Houston
country: United States
facility: Herman Memorial Hospital
state: Texas
Study officials:
affiliation: University of California San Diego, Stroke Center
name: Patrick Lyden, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lyden PD, Allgren RL, Ng K, Akins P, Meyer B, Al-Sanani F, Lutsep H, Dobak J, Matsubara BS, Zivin J. Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience. J Stroke Cerebrovasc Dis. 2005 May-Jun;14(3):107-14. doi: 10.1016/j.jstrokecerebrovasdis.2005.01.001.
citation: Guluma KZ, Hemmen TM, Olsen SE, Rapp KS, Lyden PD. A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology. Acad Emerg Med. 2006 Aug;13(8):820-7. doi: 10.1197/j.aem.2006.03.559. Epub 2006 Jun 9.
citation: Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, Wijman CA, Rapp KS, Grotta JC, Lyden PD; ICTuS-L Investigators. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010 Oct;41(10):2265-70. doi: 10.1161/STROKEAHA.110.592295. Epub 2010 Aug 19.
citation: Hemmen TM, Lyden PD. Induced hypothermia for acute stroke. Stroke. 2007 Feb;38(2 Suppl):794-9. doi: 10.1161/01.STR.0000247920.15708.fa.