Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke

Completed

Phase 1 Results

Trial Description

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.

Conditions

Interventions

  • Tissue plasminogen activator (Activase®)Drug
    Other Names: Alteplase; tPA
    Intervention Desc: tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots
    ARM 1: Kind: Experimental
    Label: Group 1
    Description: Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care.
    ARM 2: Kind: Experimental
    Label: Group 2
    Description: Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care.
    ARM 3: Kind: Experimental
    Label: Group 4
    Description: Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).
    ARM 4: Kind: Experimental
    Label: Group 6
    Description: Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).
  • Hypothermia Device
    Intervention Desc: Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System. Subjects are stratified by time to six groups.
    ARM 1: Kind: Experimental
    Label: Group 2
    Description: Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care.
    ARM 2: Kind: Experimental
    Label: Group 5
    Description: Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).
    ARM 3: Kind: Experimental
    Label: Group 6
    Description: Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care).

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety Study
  • Intervention: Factorial Assignment

Patient Involvement

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. All Patients will be randomly assigned to one of six groups based on when their stroke began. Those arriving less than 3 hours from stroke onset will be assigned to one of two groups: tPA alone or tPA with cooling (hypothermia) and those arriving 3 to 6 hours from stroke onset will be assigned to one of the four groups: tPA alone, tPA with cooling, cooling alone, or standard medical care.

Patients will be randomly assigned to one of four groups based on when their stroke began. Those arriving less than 3 hours from stroke onset will receive tPA alone or tPA with cooling (hypothermia) and those arriving 3 to 6 hours from stroke onset will be assigned to one of the four groups: tPA alone, tPA with cooling, cooling alone, or standard medical care.

Outcomes

Type Measure Time Frame Safety Issue
Primary Safety: Mortality at 90 days, hemorrhage rate, number of serious adverse events. Efficacy: NIHSS at 24 hours, Modified Ranken Scale score and NIHSS at 30 days, Stroke Volume on day 30 CT, incidence and volume of hemorrhage on CT scans.
Primary Incidence and volume of hemorrhage on CT 48 hours post onset Yes
Secondary Incidence of AE and SAE 90 days post onset Yes
Secondary Mortality in both groups testing whether hypothermia improves mortality after stroke 90 Day Yes
Secondary NIHSS at the end of hypothermia Hour 23.5 +/- 30 minutes of hypothermia No
Secondary Modified Rankin and NIHSS 30 and 90days No
Secondary CT lesion volume 30 days No

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