Acute Ischemic Stroke
Conditions
Keywords
stroke, hypothermia, thrombolysis, imaging, collateral circulation, recanalization, reperfusion
Brief summary
The primary objective of this Phase 2 HASTIER study, as an ancillary study to ICTuS 2, is to compare key imaging measurements for serial changes in recanalization and reperfusion between hypothermia and normothermia treatment arms as intermediate outcomes of treatment effect. Secondary exploratory analyses include imaging of the neurovascular impact of reperfusion with hypothermia and tPA, including blood-brain barrier changes or permeability, hemorrhagic transformation, and infarct growth.
Detailed description
A prospective imaging ancillary study coincides with recruitment of ICTuS 2 by using currently available imaging tools at a subset of multicenter sites. HASTIER will evaluate therapeutic response with imaging outcome measures for recanalization and reperfusion. Key scientific objectives include the evaluation of hypothermia on benchmark recanalization and reperfusion rates in 120 cases of middle cerebral artery (MCA) stroke. Recanalization will be measured with Thrombolysis in Myocardial Infarction (TIMI) score change from baseline-36 hour CT/MRI angiography. Reperfusion will be measured with Tmax \> 6s lesion volume change from baseline-36 hour CT/MRI perfusion imaging. Secondary outcomes will be measured with serial changes in permeability abnormalities derived from CT/MRI perfusion imaging, hemorrhagic transformation, and infarct growth from baseline-36 hours. Correlation of these imaging parameters with clinical outcomes will provide insight to accelerate research during these translational steps in hypothermia treatment for acute ischemic stroke.
Interventions
OTHERIV t-PA and normothermia
DEVICEIV-tPA and hypothermia
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
* Eligible for inclusion in the ICTuS 2/3 trial. * Diagnosis of MCA stroke, confirmed by M1 or M2 proximal MCA occlusion on CT/MRI angiography.
Exclusion criteria
* Kidney dysfunction of such severity as to preclude routine administration of contrast media for CT/MRI angiography or perfusion imaging. Severe kidney dysfunction is defined by the American College of Radiology recommendations for use of contrast media. * Known adverse reaction or allergy to such contrast media.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Recanalization | 36 hours | To determine whether hypothermia alters recanalization with standard thrombolytic treatment with intravenous (IV) tissue plasminogen activator (tPA) for acute ischemic stroke in humans. The hypothesis is that hypothermia does not impair recanalization (opening of the artery). Recanalization will be measured with Thrombolysis in Myocardial Infarction (TIMI) score change from baseline angiography to 36 hour angiography. TIMI is cored per published definition. Additional data for secondary analyses were not acquired to permit analyses. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normothermia IV t-PA and normothermia | 2 |
| Hypothermia IV t-PA and hypothermia | 4 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
Baseline characteristics
| Characteristic | Normothermia | Hypothermia | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United States | 2 participants | 4 participants | 6 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 4 / 4 |
| serious Total, serious adverse events | 1 / 2 | 1 / 4 |
Outcome results
Primary
Number of Participants With Recanalization
To determine whether hypothermia alters recanalization with standard thrombolytic treatment with intravenous (IV) tissue plasminogen activator (tPA) for acute ischemic stroke in humans. The hypothesis is that hypothermia does not impair recanalization (opening of the artery). Recanalization will be measured with Thrombolysis in Myocardial Infarction (TIMI) score change from baseline angiography to 36 hour angiography. TIMI is cored per published definition. Additional data for secondary analyses were not acquired to permit analyses.
Time frame: 36 hours
Population: Recanalization at 36 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Normothermia | Number of Participants With Recanalization | 2 Participants |
| Hypothermia | Number of Participants With Recanalization | 3 Participants |