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

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ClinicalTrials.gov Identifier: NCT05203224
Recruitment Status : Recruiting
First Posted : January 24, 2022
Last Update Posted : May 24, 2022
Sponsor:
Information provided by (Responsible Party):
University of Melbourne

Study Description
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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 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.

Condition or disease Intervention/treatment Phase
Ischemic Stroke Drug: Dornase Alfa Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Bayesian Optimised Phase 2 dose-finding umbrella trial
Masking: None (Open Label)
Masking Description: No blinding given single arm study but Independent core laboratory adjudication of the primary outcome, mRS (secondary outcome) performed by central assessor.
Primary Purpose: Treatment
Official Title: Improving Early Reperfusion With Adjuvant Dornase Alfa in Large Vessel Ischemic Stroke (EXTEND-IA DNase)
Actual Study Start Date : February 18, 2022
Estimated Primary Completion Date : September 30, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ischemic Stroke

Arms and Interventions
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Arm Intervention/treatment
Experimental: Intravenous Dornase alfa (DNase)
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
Intravenous Dornase alfa
Other Names:
  • DNase
  • Pulmozyme


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures:
  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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05203224


Contacts
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Contact: Bruce CV Campbell, MBBS PhD 0393427000 bruce.campbell@mh.org.au

Locations
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Australia, Queensland
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia, 4102
Contact: Carol Bendall    +61 7 3176 1499    carol.bendall@health.qld.gov.au   
Principal Investigator: Michael Devlin, MBBS         
Australia, South Australia
Royal Adelaide Hospital Not yet recruiting
Adelaide, South Australia, Australia, 5000
Contact: Jennifer Cranefield, RN    +61 8 7074 2900    jennifer.cranefield@sa.gov.au   
Principal Investigator: Timothy Kleinig, MBBS PhD         
Australia, Victoria
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia, 3050
Contact: Amy McDonald, RN    +61 3 9342 4424    amy.mcdonald@mh.org.au   
Principal Investigator: Bruce Campbell, MBBS PhD         
Sponsors and Collaborators
University of Melbourne
Investigators
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Principal Investigator: Bruce CV Campbell, MBBS PhD University of Melbourne
More Information
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Responsible Party: University of Melbourne
ClinicalTrials.gov Identifier: NCT05203224    
Other Study ID Numbers: MBC2101
First Posted: January 24, 2022    Key Record Dates
Last Update Posted: May 24, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient data will be uploaded to the Virtual Stroke Trials Archive (http://www.virtualtrialsarchives.org/vista/) 2 years after the publication of the primary manuscript. Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA steering committee.
Time Frame: 2 years after the publication of the primary manuscript
Access Criteria: Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA steering committee.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by University of Melbourne:
thrombolysis
thrombolytic
endovascular thrombectomy
 tenecteplase
dornase alfa
DNase
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Infarction
Necrosis