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The Intravascular Cooling in the Treatment of Stroke 2/3 Trial (ICTuS2/3)

This study has been terminated.
(The ICTuS 2 portion of the trial has been halted and data will be analyzed.)
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
The University of Texas Health Science Center, Houston
Information provided by (Responsible Party):
Patrick Lyden, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT01123161
First received: April 27, 2010
Last updated: February 18, 2017
Last verified: February 2017
  Purpose
The purpose of this trial is to determine whether the combination of thrombolysis and hypothermia is superior to thrombolysis alone for the treatment of acute ischemic stroke.

Condition Intervention Phase
Stroke, Acute
Device: hypothermia and anti-shivering treatment
Drug: Group1: IV t-PA and normothermia
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:
Randomized to normothermia or hypothermia
Masking: Outcomes Assessor
Primary Purpose: Treatment
Official Title: Phase 2/3 Study of Intravenous Thrombolysis and 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:
  • The Primary Outcome is the Proportion of Patients Achieving a Favorable Outcome Defined as Modified Rankin Scale Score of 0 or 1, Assessed 90 Days After Treatment. [ Time Frame: 90 days ]
    Modified Rankin describes disability: 0 is free of any disability or symptoms, 6 is death, and higher grades between 0 and 6 reflect progressively greater disability

  • Incidence of Any Intracranial Hemorrhage (ICH) Within 48 Hours of Stroke Onset [ Time Frame: 48 hours ]
    Incidence (number) of any intracranial hemorrhage (ICH) (whether or not symptomatic) within 48 hours of stroke onset will be presented by treatment group and overall.

  • Incidence of Any Symptomatic Intracranial Hemorrhage (sICH) Within 48 Hours of Stroke Onset [ Time Frame: 48 hours ]
    Incidence (number) of Symptomatic ICH (sICH) within 48 hours of stroke onset will be presented by treatment group and overall. Patients with neuroworsening (4 or more point increase in NIHSS , or a decline in the NIHSS consciousness item 1A score of more than 1 point, or a motor deterioration lasting more than 8 hours, all not due to iatrogenic cause) and hemorrhage seen on brain images in whom the investigator attributes the clinical change to the hemorrhage.

  • Incidence of Pneumonia [ Time Frame: 7 days or discharge whichever comes first ]
    Number subjects diagnosed with pneumonia according to CDC criteria will be presented by treatment group and overall, regardless of seriousness

  • 90 Day Mortality [ Time Frame: 90 days ]
    Mortality prior to the 90-day evaluation.


Secondary Outcome Measures:
  • The Barthel Index Measure of Activities of Daily Living; [ Time Frame: 90 days ]
    The Barthel index measures independence in activities of daily living from 0 (worst) to 100 (best) in 5 point increments. Higher scores between 0 and 100 reflect progressively greater levels of independence. Scores were dichotomized at 90 so that a score of 95 or 100 was considered a successful treatment.

  • NIHSS Scores at 90 Days [ Time Frame: 90 days ]
    The National Institutes of Health Stroke Scale (NIHSS) is used to quantify neurological deficit. The scale ranges from 0 (best) to 42 points (worst). Between scores of 0 to 42, higher values reflect progressively greater deficit.


Enrollment: 120
Study Start Date: June 2010
Study Completion Date: May 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group1: IV t-PA and normothermia
IV tpa and normothermia
Drug: Group1: IV t-PA and normothermia
Group 1 will t-PA as standard of care and normothermia
Active Comparator: Group 2 : IV t-PA and hypothermia and anti-shivering treatment
IV tpa and hypothermia and anti-shivering treatment
Device: hypothermia and anti-shivering treatment
Hypothermia is induced using the Celsius Control™ System. Shivering is treated with buspirone, meperidine and surface warming
Other Name: cooling

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.

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.

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.

There are two study groups - tPA alone or tPA with cooling (hypothermia). Participants will be randomly assigned to one of the two study groups. 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:   22 Years to 82 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 22 to 82 years old inclusive
  2. Patient receiving IV rt-PA using standard guidelines
  3. NIHSS score ≥ 7 and ≤ 20 (right hemisphere) or ≥ 7 and ≤ 24 (left hemisphere) at the time of randomization
  4. Pre-stroke mRS 0-1
  5. Able to begin endovascular phase of hypothermia within 2 hours of tPA completion
  6. Written Informed Consent, signed and dated by the patient (or patient's authorized representative)

Exclusion Criteria:

  1. Etiology other than ischemic stroke
  2. Item 1a on NIHSS > 1 at the time of randomization
  3. Clinical symptoms consistent with brainstem or cerebellar stroke
  4. Classic lacunar syndrome with imaging confirmation of small deep ischemia, but randomization will not be delayed for neuroimaging other than initial scan to exclude hemorrhage
  5. Known contraindications to hypothermia, such as known hematologic dyscrasias that affect thrombosis (cryoglobulinemia, Sickle cell disease, serum cold agglutinins), or vasospastic disorders such as Raynaud's or thromboangiitis obliterans
  6. Known co-morbid conditions that are likely to complicate therapy in the opinion of the investigator, e.g., i. Heart failure (NYHA class III and IV)* ii. Uncompensated arrhythmia iii. Severe Liver disease iv. History of pelvic or abdominal mass likely to compress inferior vena cava v. IVC filters vi. HIV positive vii. Clinically active hypo or hyperthyroidism viii. Renal insufficiency likely to impair meperidine clearance ix. Chronic ethanol abuse x. History of HIT (heparin induced thrombocytopenia)
  7. Pregnancy (All women of child-bearing potential must have a negative pregnancy test, urine or blood, prior to therapy.)
  8. Medical conditions likely to interfere with patient assessment.
  9. Known allergy to meperidine or buspirone
  10. Currently taking or used within previous 14 days MAO-I class of medication.
  11. Life expectancy < 6 months
  12. Not likely to be available for long-term follow-up
  13. Use, or planned use, of intra-arterial thrombolysis, mechanical clot removal, or other experimental or approved acute therapy for this stroke event
  14. Chest radiograph or clinical presentation suggestive of pneumonia or clinically significant pulmonary edema at baseline.
  15. Temperature upon admission greater than or equal to 38°C
  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: NCT01123161

  Show 31 Study Locations
Sponsors and Collaborators
University of California, San Diego
National Institute of Neurological Disorders and Stroke (NINDS)
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Patrick D. Lyden, MD Cedars-Sinai Medical Center
Study Director: Thomas M. Hemmen, MD, PhD University of California, San Diego
Study Director: James C. Grotta, MD The University of Texas Health Science Center, Houston
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Patrick Lyden, Principal Investigator, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT01123161     History of Changes
Other Study ID Numbers: ICTuS2/3
P50NS044148 ( US NIH Grant/Contract Award Number )
P50NS044227 ( US NIH Grant/Contract Award Number )
Study First Received: April 27, 2010
Results First Received: September 29, 2016
Last Updated: February 18, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of California, San Diego:
Hypothermia
Molecular Mechanisms of Pharmacological Action
Cerebral Infarction
Hematologic Agents
Stroke
Nervous System Diseases
Vascular Diseases
Tissue Plasminogen Activator
Central Nervous System Diseases
Fibrinolytic Agents
Cardiovascular Agents
Body Temperature Changes
Brain Diseases
Cerebrovascular Disorders
Pharmacologic Actions
Signs and Symptoms
Fibrin Modulating Agents
Therapeutic Uses
Brain Ischemia
Cardiovascular Diseases
Brain Infarction
Plasminogen
cooling
tPA
thrombolysis

Additional relevant MeSH terms:
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Molecular Mechanisms of Pharmacological Action
Plasminogen
Fibrinolytic Agents
Fibrin Modulating Agents

ClinicalTrials.gov processed this record on April 21, 2017