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 (measured by MRI criteria) at 3 - 9 hours post onset of stroke 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
Commonwealth Scientific and Industrial Research Organisation, Australia
University of Melbourne
Melbourne Health
The Florey Institute of Neuroscience and Mental Health
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
1. Patients presenting with hemispheric acute ischaemic stroke 2. Patient, family member or legally responsible person depending on local ethics requirements has given informed consent 3. Patient's age is ≥18 years 4. Treatment onset can commence within ≥ 3 - 9 hours after stroke onset according to registered product information, or within 4.5 - 9 hours according to locally accepted guidelines\*. (\*Guidelines are currently under international review - advisory statement issued by the Stroke Council, American Heart Association and American Stroke Association) 5. 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. 6. NIHSS score of ≥ 4 - 26 with clinical signs of hemispheric infarction. 7. Penumbral mismatch - A hypo-perfusion to core volume ratio of greater than 1.2 and an absolute difference greater than 10mL (using a MR or CT Tmax \> 6 second delay) between perfusion lesion and MR-DWI or CT-CBF core lesion. 8. An ischaemic core lesion volume of less than or equal to 70 ml using MR-DWI or CT-CBF \*\* Patients may be consented before or after penumbral screening depending upon local practice. The entire cohort of patients consented onto the study will be followed up with clinical assessments and biomarker studies regardless of eligibility for randomisation to treatment based on penumbral mismatch criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Modified Rankin Scale (mRS) 0-1 | 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of life (Stroke Impact Scale) | 3 and 12 months | — |
| Categorical shift in modified Rankin Score (mRS) | 3 months | — |
| Change in ≥ 8 NIHSS points or reaching ≤ 1 on this scale | 3 months | — |
| Death due to any cause | 3 months | — |
| Depression (Montgomery-Asberg Depression Rating Scale [MADRS]) | 3 and 12 months | — |
| Reperfusion | 24 hours | — |
| Recanalisation | 24 hours | — |
| Infarct growth | 24 hours | Difference in volumetric DWI volume between baseline and 24 hour MRI |
| Recurrent stroke | 3 and 12 months | — |
| Symptomatic ICH | 24 hours | Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS |
Countries
Australia, Finland, New Zealand
Outcome results
None listed