Ischemic Stroke
Conditions
Keywords
thrombolysis, thrombolytic, endovascular thrombectomy, tenecteplase, dornase alfa, DNase
Brief summary
Patients presenting to the emergency department with acute ischemic stroke, who are are eligible for standard intravenous thrombolytic therapy within 4.5 hours of stroke onset will be assessed for major vessel occlusion to determine their eligibility for the trial. All participants will receive intravenous tenecteplase (or alteplase due to manufacturer shortage) and endovascular thrombectomy as standard care. The trial is a Bayesian Optimised Phase 2 dose-finding umbrella trial (single arm versus objective performance criterion of 20% substantial reperfusion prior to endovascular thrombectomy based on the EXTEND-IA TNK trials NCT02388061, NCT03340493). The aim is to determine the optimal dose of intravenous dornase alfa (recombinant human DNase 1) with sufficient promise to take forward in a seamless phase 2b/3 design.
Interventions
DRUGDornase Alfa
Intravenous Dornase alfa
Sponsors
University of Melbourne
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
No blinding given single arm study but Independent core laboratory adjudication of the primary outcome, mRS (secondary outcome) performed by central assessor.
Intervention model description
Bayesian Optimised Phase 2 dose-finding umbrella trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients presenting with acute ischemic stroke eligible, using standard criteria, to receive IV thrombolytics within 4.5 hours of stroke onset 2. Patient's age is ≥18 years 3. Intention to perform endovascular thrombectomy Imaging inclusion criteria 4. Arterial occlusion on CTA or MRA of the ICA, M1, M2 or basilar artery
Exclusion criteria
1. Intracranial hemorrhage (ICH) identified by CT or MRI 2. Rapidly improving symptoms at the discretion of the investigator 3. Pre-stroke mRS score of ≥ 4 (indicating previous disability) 4. Hypodensity in \>1/3 MCA territory or equivalent proportion of basilar artery territory on non-contrast CT 5. Contraindication to imaging with contrast agents 6. Any terminal illness such that patient would not be expected to survive more than 1 year 7. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study. 8. Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with substantial angiographic reperfusion or absence of retrievable intracranial thrombus at initial angiogram without symptomatic intracerebral hemorrhage | 24 hours post-treatment | composite outcome of reperfusion on initial angiogram (day 0 - expanded Treatment In Cerebral Infarction \[eTICI\] 2b-3 or no retrievable intracranial thrombus) and assessment of symptomatic intracerebral hemorrhage on brain imaging 24h post-treatment. eTICI 2b-3 indicates reperfusion of \>50% of the initially involved arterial territory. |
Other
| Measure | Time frame | Description |
|---|---|---|
| modified Rankin Scale (mRS) 0-1 or no change from baseline at 3 months | 3 months post stroke | versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score |
| modified Rankin Scale (mRS) 0-2 or no change from baseline at 3 months | 3 months post stroke | versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score |
| Proportion of patients with 8 point reduction in NIHSS or reaching 0-1 at 3 days (early neurological improvement) | 3 days post stroke | versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score |
| modified Rankin Scale (mRS) at 3 months | 3 months post stroke | ordinal analysis versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline National Institutes of Health Stroke Scale (NIHSS) score. mRS is a functional outcome/disability score from 0 (no disability) to 6 (death). NIHSS is a neurological impairment score from 0 (no deficit) to 42 (death) |
| Symptomatic intracranial hemorrhage (SICH) | 36 hours post treatment | Symptomatic intracranial hemorrhage includes any sub-arachnoid bleeding associated with clinical symptoms and symptomatic intracerebral hemorrhage (SICH). SICH is defined as Intracerebral hemorrhage (parenchymal hematoma type 2 - PH2 within 36 hours of treatment) combined with neurological deterioration leading to an increase of ≥4 points on the NIHSS from baseline, or death |
| Death due to any cause | up to 3 months post stroke | versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS |
| Proportion of patients with near-complete reperfusion (eTICI 2c/3) at conclusion of the endovascular procedure | day 0 (end of endovascular thrombectomy) | versus EXTEND-IA TNK I & II historical control |
Countries
Australia
Contacts
Primary ContactBruce CV Campbell, MBBS PhD
Outcome results
None listed