Stroke
Conditions
Keywords
Stroke, Thrombolysis, MRI, Echoplanar, Penumbra
Brief summary
To determine whether the extent of the ischemic penumbra apparent on perfusion-diffusion MRI can be used to identify patients who would respond positively and safely to tissue plasminogen activator (tPA) beyond 3 hours post-stroke.
Interventions
DRUGAlteplase t-PA
Sponsors
Boehringer Ingelheim
Melbourne Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who present: * with acute hemispheric stroke within 3-6 hours of onset, * have at least moderate limb weakness, * a National Institute of Health Stroke Scale (NIHSS) score \> 4, * had a pre-stroke modified Rankin Scale (MRS) score of 0 - 2 * and who are able to undergo CT and MRI, are eligible for this study.
Exclusion criteria
* Females who are pregnant or breast-feeding, * persons who have CT-verified hemorrhagic stroke, major ischemia ( \> 33% of the middle cerebral artery (MCA) territory infarcted), subarachnoid hemorrhage, arteriovenous malformation, aneurysm, intracranial neoplasm that is terminal or poses a risk of hemorrhage , * are comatose or severely obtunded with fixed eye deviation and complete hemiplegia, * have had another stroke within the past 6 weeks, * have had a seizure prior to the administration of the study drug, * have active peptic ulceration, bleeding diatheses, previous intracerebral hemorrhage, * blood pressure \> 185/110, * major surgery or trauma within the past 30 days, or any other contraindications to tPA * have a presumed septic embolus or a myocardial infarction within the past 30 days * blood glucose values are \< 2.8 or \> 22.0 mmol/L, * pacemakers, aneurysm clips, implanted devices, claustrophobia, or any other contraindications to MRI, * decreased consciousness, * rapid clinical improvement, * confounding neurological condition (e.g. dementia), * any other life-threatening illness, or who are participating in another clinical trial, will be excluded from this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Hypothesis - lesion growth | — |
| In patients with penumbra, there will be attenuation of lesion growth (outcome T2 lesion volume - acute DWI volume ) with tPA. | — |
Secondary
| Measure | Time frame |
|---|---|
| Favourable functional outcome (mRS 0-2) will be more likely in patients with penumbra receiving tPA. | — |
| That the proportion of patients achieving good neurological outcome (an 8 point improvement in NIH-SS or outcome NIH-SS of 0, 1) will be greater in those patients with a penumbra receiving tPA. | — |
| Secondary Hypotheses | — |
| Reperfusion (greater than 90% PWI lesion reduction, or recanalisation on MRA, between the acute and sub-acute interval), will be increased (in patients with penumbra) receiving tPA. | — |
| In patients with malignant mismatch (Definition DWI 100ml or more and / or PWI 100ml or more) there will be unfavourable clinical outcome (even if there is attenuation of growth). | — |
| Symptomatic hemorrhagic transformation (sICH) will be predicted by the size of the baseline DWI volume in those patients receiving tPA. | — |
| In the non-penumbral group, lesion growth will be lower and will not be attenuated by tPA. | — |
Countries
Australia, Belgium, New Zealand, United Kingdom
Outcome results
None listed