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Completed

NCT Number: NCT05203224

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

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.

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Key information

Conditions

Ischemic Stroke Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Stroke Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Princess Alexandra Hospital, Brisbane, Queensland, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dornase Alfa

Drug

Intravenous Dornase alfa

Other names: DNase, Pulmozyme

Primary outcomes

  1. Proportion of patients with substantial angiographic reperfusion or absence of retrievable intracranial thrombus at initial angiogram without symptomatic intracerebral hemorrhage

    Time frame: 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 outcomes

  1. modified Rankin Scale (mRS) at 3 months

    Time frame: 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)

  2. modified Rankin Scale (mRS) 0-1 or no change from baseline at 3 months

    Time frame: 3 months post stroke

    versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score

  3. modified Rankin Scale (mRS) 0-2 or no change from baseline at 3 months

    Time frame: 3 months post stroke

    versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score

  4. Proportion of patients with 8 point reduction in NIHSS or reaching 0-1 at 3 days (early neurological improvement)

    Time frame: 3 days post stroke

    versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score

  5. Proportion of patients with near-complete reperfusion (eTICI 2c/3) at conclusion of the endovascular procedure

    Time frame: day 0 (end of endovascular thrombectomy)

    versus EXTEND-IA TNK I & II historical control

  6. Symptomatic intracranial hemorrhage (SICH)

    Time frame: 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"

  7. Death due to any cause

    Time frame: up to 3 months post stroke

    versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS

Sponsors and collaborators

Lead sponsor

University of Melbourne

Other

Registry information

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Jan 24, 2022
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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