Stroke
Conditions
Keywords
ischemic stroke, ischemic penumbra, magnetic resonance imaging, MRI, diffusion imaging, DWI, perfusion imaging, PWI, thrombolysis, alteplase, tPA, EPITHET
Brief summary
The primary hypothesis being tested in this trial is that ischaemic stroke patients selected with significant penumbral mismatch (according to imaging criteria) at 4.5 (or 3 hours depending on local guidelines) - 9 hours post onset of stroke or after 'wake up stroke' (WUS) will have improved clinical outcomes when given intravenous tissue plasminogen activator (tPA) compared to placebo.
Interventions
0.9 mg/kg up to a maximum of 90mg, intravenous, 10% as bolus and the remainder over 1 hour
DRUGPlacebo
placebo provided as 50mg lyophilised powder to be reconstituted with sterile water in glass vials indistinguishable from active drug
Sponsors
China Medical University Hospital
Neuroscience Trials Australia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients presenting with hemispheric acute ischaemic stroke * Patient, family member or legally responsible person depending on local ethics requirements has given informed consent * Patient's age is ≥18 years (or as per local requirements) * Treatment onset can commence within 4.5 - 9 hours after stroke onset according to registered product information, or within 3 - 9 hours according to locally accepted guidelines. * Patients who wake with stroke may be included if neurological and other
Exclusion criteria
are satisfied. These 'wake up' strokes are defined as having no symptoms at sleep onset, but stroke symptoms on waking. The time of stroke onset is to be taken as the mid-point between sleep onset (or last known to be normal) and time of waking. The maximum time window for randomisation is then 9 hours from the mid-point as described. * Significant neurological deficit (eg. NIHSS score of ≥ 4 - 26) with clinical signs of hemispheric infarction. * Penumbral mismatch - A hypo-perfusion to core volume ratio of greater than 1.2, and an absolute difference greater than 10ml (using a Magnetic Resonance (MR) or Computed Tomography (CT) Tmax \> 6 second delay), between perfusion lesion and MR-DWI or Computed Tomography-Cerebral Blood Flow (CT-CBF) core lesion. * An infarct core lesion of less than or equal to 70ml using MR-DWI or CT-CBF
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Modified Rankin Scale (mRS) 0-1 | 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in ≥ 8 National Institutes of Health Stroke Scale (NIHSS) points or reaching ≤ 1 on this scale | 3 months | — |
| Death due to any cause | 3 months | — |
| Symptomatic Intracerebral Hemorrhage (ICH) | 24 hours | Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS |
| Categorical shift in modified Rankin Score (mRS) | 3 months | — |
| Recanalisation | 24 hours | — |
| Infarct growth | 24 hours | Difference in volumetric Diffusion Weighted Image (DWI) volume between baseline and 24 hour Magnetic Resonance Imaging (MRI) |
| Recurrent stroke | 3 and 12 months | — |
| Reperfusion | 24 hours | — |
Countries
Taiwan
Outcome results
None listed