Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke - Full Text View

Sponsors and Collaborators:	University of California, San Diego National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier:	NCT00283088

Purpose

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.

Condition	Intervention	Phase
Stroke	Procedure: hypothermia Drug: tissue plasminogen activator	Phase I

MedlinePlus related topics: Hypothermia

Drug Information available for: Alteplase Tissue-type plasminogen activator

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Safety Study
Official Title:	Phase 1 Study of Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke

Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):

Primary Outcome Measures:

Incidence and volume of hemorrhage on CT [ Time Frame: 48 hours post onset ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Incidence of AE and SAE [ Time Frame: 90 days post onset ] [ Designated as safety issue: Yes ]
Mortality [ Time Frame: 90 Day ] [ Designated as safety issue: Yes ]
NIHSS at the end of hypothermia [ Time Frame: Hour 23.5 +/- 30 minutes of hypothermia ] [ Designated as safety issue: No ]
Modified Rankin and NIHSS [ Time Frame: 30 and 90days ] [ Designated as safety issue: No ]
CT lesion volume [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	130
Study Start Date:	October 2003
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1: Active Comparator Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care.	Drug: tissue plasminogen activator tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots
Group 2: Active Comparator Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care.	Procedure: hypothermia Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System. Subjects are stratified by time to six groups. Drug: tissue plasminogen activator tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots
Group 3: No Intervention 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 4: Active Comparator Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).	Drug: tissue plasminogen activator tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots
Group 5: Active Comparator Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).	Procedure: hypothermia 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: Active Comparator Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).	Procedure: hypothermia Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System. Subjects are stratified by time to six groups. Drug: tissue plasminogen activator tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots

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

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00283088

Locations

United States, California
University of California San Diego, Hillcrest Medical Center
San Diego, California, United States, 92103
University of California San Diego, Thornton Hospital
San Diego, California, United States, 92037
Scripps Mercy Hospital
San Diego, California, United States, 92103
Stanford Medical Center
Palo Alto, California, United States, 94304
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102
United States, Missouri
Saint Louis University Medical Center
St. Louis, Missouri, United States, 63110
United States, Texas
Herman Memorial Hospital
Houston, Texas, United States, 77030

Sponsors and Collaborators

University of California, San Diego

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:

Patrick Lyden, MD

University of California San Diego, Stroke Center

More Information

Publications:

Lyden Patrick D., Allgren Robin L., Ng Ken, Akins Paul, Meyer Brett, Fahmi Al-Sanani, Lutsep Helmi, Dobak John, Matsubara Bradley S., Zivin Justin; Intravascular Cooling in the Treatment of Stroke (ICTuS): Early Clinical Experience: Journal of Stroke and Cerebrovascular Diseases, Vol. 14, No. 3 (May - June), 2005: pp 107 - 114.

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. Epub 2006 Jun 9.

Hemmen TM, Guluma KZ, Wijman CA, Cruz-Flores S, Meyer BC, Rapp KS, Klos BR, Raman R, Lyden PD. Intravenous Thrombolysis Plus Hypothermia for acute Treatment of Ischemic Stroke (ICTuS-L) Stroke 37:706, 2006.

Hemmen TM, Lyden PD. Induced hypothermia for acute stroke. Stroke. 2007 Feb;38(2 Suppl):794-9. Review.

Responsible Party:	University of California San Diego, Stroke Center ( Patrick Lyden, MD, Director, UCSD Stroke Center, )
Study ID Numbers:	R01NS44148LYDEN
Study First Received:	January 26, 2006
Last Updated:	January 6, 2009
ClinicalTrials.gov Identifier:	NCT00283088
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):

stroke
hypothermia
cooling

tissue plasminogen activator
tPA
thrombolysis

Study placed in the following topic categories:

Hypothermia
Cerebral Infarction
Stroke
Vascular Diseases
Central Nervous System Diseases
Tissue Plasminogen Activator
Ischemia

Brain Diseases
Cerebrovascular Disorders
Signs and Symptoms
Brain Ischemia
Brain Infarction
Infarction
Plasminogen

Additional relevant MeSH terms:

Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Hematologic Agents
Nervous System Diseases

Fibrinolytic Agents
Cardiovascular Diseases
Cardiovascular Agents
Body Temperature Changes
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009