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. |
Countries
Australia
Contacts
PRINCIPAL_INVESTIGATORBruce CV Campbell, MBBS PhD
University of Melbourne
Outcome results
None listed