Improving Early Reperfusion With Adjuvant Dornase Alfa in Large Vessel Ischemic Stroke (EXTEND-IA DNase)

Study Overview
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Brief Summary
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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 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.

Official Title
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Improving Early Reperfusion With Adjuvant Dornase Alfa in Large Vessel Ischemic Stroke (EXTEND-IA DNase)

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: Dornase Alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with acute ischemic stroke eligible, using standard criteria, to receive IV thrombolytics within 4.5 hours of stroke onset Patient's age is ≥18 years Intention to perform endovascular thrombectomy Imaging inclusion criteria Arterial occlusion on CTA or MRA of the ICA, M1, M2 or basilar artery Exclusion Criteria: Intracranial hemorrhage (ICH) identified by CT or MRI Rapidly improving symptoms at the discretion of the investigator Pre-stroke mRS score of ≥ 4 (indicating previous disability) Hypodensity in >1/3 MCA territory or equivalent proportion of basilar artery territory on non-contrast CT Contraindication to imaging with contrast agents Any terminal illness such that patient would not be expected to survive more than 1 year 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. Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Bayesian Optimised Phase 2 dose-finding umbrella trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Dornase alfa (DNase)<br>Patients will receive a single intravenous dose of dornase alfa (at either 0.125mg/kg, 0.25mg/kg, or 0.5mg/kg in escalating tiers), administered as a bolus over  30 seconds. | Drug: Dornase Alfa<br>* Intravenous Dornase alfa<br>* Other names: Pulmozyme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with substantial angiographic reperfusion or absence of retrievable intracranial thrombus at initial angiogram without symptomatic intracerebral hemorrhage | 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. | 24 hours post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombolysis, thrombolytic, endovascular thrombectomy, tenecteplase, dornase alfa, DNase