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

Phase 2

Recruiting

• Conditions: Ischemic Stroke
• Interventions: Drug: Dornase Alfa

• Registration Number: NCT05203224
• Lead Sponsor: University of Melbourne

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-10
• Study First Submitted QC: 2022-01-10
• Study First Posted: 2022-01-24
• Study Start: 2022-02-18
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-26
• Last Update Posted: 2024-06-28
• Primary Completion: 2025-09-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intravenous Dornase alfa (DNase)	Dornase Alfa	Patients will receive a single intravenous dose of dornase alfa (at either 0.125mg/kg, 0.25mg/kg, 0.5mg/kg or 1mg/kg in escalating tiers), administered as a bolus over \~30 seconds.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (3)

Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia