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

Phase 2RecruitingNCT05203224

University of Melbourne300 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

300

Conditions

Ischemic Stroke

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

Princess Alexandra Hospital

Brisbane, Queensland, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

NOT_YET_RECRUITING

Royal Melbourne Hospital

Melbourne, Victoria, Australia

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 24 hours post-treatment