Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00283088
First received: January 26, 2006
Last updated: January 11, 2011
Last verified: January 2009
  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 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

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 in both groups testing whether hypothermia improves mortality after stroke [ 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
Study Completion Date: May 2009
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: tissue plasminogen activator
tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots
Active Comparator: 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.
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
No Intervention: 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).
Active Comparator: 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).
Drug: tissue plasminogen activator
tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots
Active Comparator: 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).
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.

Active Comparator: 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).
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
Stanford Medical Center
Palo Alto, California, United States, 94304
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
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
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.
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.

Responsible Party: Patrick Lyden, MD, Director, UCSD Stroke Center,, University of California San Diego, Stroke Center
ClinicalTrials.gov Identifier: NCT00283088     History of Changes
Other Study ID Numbers: P50NS44148LYDEN
Study First Received: January 26, 2006
Last Updated: January 11, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
stroke
hypothermia
cooling
tissue plasminogen activator
tPA
thrombolysis

Additional relevant MeSH terms:
Hypothermia
Stroke
Cerebral Infarction
Body Temperature Changes
Signs and Symptoms
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on August 28, 2014