Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke

NCT ID: NCT00283088

Last Updated: 2011-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-10-31

Study Completion Date

2009-05-31

Brief Summary

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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

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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.

Conditions

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Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1

Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care.

Group Type ACTIVE_COMPARATOR

tissue plasminogen activator

Intervention Type DRUG

tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots

Group 2

Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care.

Group Type ACTIVE_COMPARATOR

hypothermia

Intervention Type PROCEDURE

Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System.

Subjects are stratified by time to six groups.

tissue plasminogen activator

Intervention Type DRUG

tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots

Group 3

Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).

Group Type NO_INTERVENTION

No interventions assigned to this group

Group 4

Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).

Group Type ACTIVE_COMPARATOR

tissue plasminogen activator

Intervention Type DRUG

tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots

Group 5

Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).

Group Type ACTIVE_COMPARATOR

hypothermia

Intervention Type PROCEDURE

Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System.

Subjects are stratified by time to six groups.

Group 6

Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).

Group Type ACTIVE_COMPARATOR

hypothermia

Intervention Type PROCEDURE

Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System.

Subjects are stratified by time to six groups.

tissue plasminogen activator

Intervention Type DRUG

tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots

Interventions

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hypothermia

Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System.

Subjects are stratified by time to six groups.

Intervention Type PROCEDURE

tissue plasminogen activator

tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role lead

Responsible Party

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University of California San Diego, Stroke Center

Principal Investigators

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Patrick Lyden, MD

Role: PRINCIPAL_INVESTIGATOR

University of California San Diego, Stroke Center

Locations

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Stanford Medical Center

Palo Alto, California, United States

Site Status

University of California San Diego, Thornton Hospital

San Diego, California, United States

Site Status

Scripps Mercy Hospital

San Diego, California, United States

Site Status

University of California San Diego, Hillcrest Medical Center

San Diego, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Saint Louis University Medical Center

St Louis, Missouri, United States

Site Status

Herman Memorial Hospital

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 17904009 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16766740 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20724711 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17261741 (View on PubMed)

Other Identifiers

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P50NS044148

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P50NS44148LYDEN

Identifier Type: -

Identifier Source: org_study_id

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