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

NCT ID: NCT05203224

Last Updated: 2024-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-18

Study Completion Date

2025-12-31

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 (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

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Conditions

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Ischemic Stroke

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Bayesian Optimised Phase 2 dose-finding umbrella trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

No blinding given single arm study but Independent core laboratory adjudication of the primary outcome, mRS (secondary outcome) performed by central assessor.

Study Groups

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Intravenous Dornase alfa (DNase)

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.

Group Type EXPERIMENTAL

Dornase Alfa

Intervention Type DRUG

Intravenous Dornase alfa

Interventions

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Dornase Alfa

Intravenous Dornase alfa

Intervention Type DRUG

Other Intervention Names

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DNase Pulmozyme

Eligibility Criteria

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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
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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Melbourne

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bruce CV Campbell, MBBS PhD

Role: PRINCIPAL_INVESTIGATOR

University of Melbourne

Locations

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Princess Alexandra Hospital

Brisbane, Queensland, Australia

Site Status RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status NOT_YET_RECRUITING

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Bruce CV Campbell, MBBS PhD

Role: CONTACT

0393427000

Facility Contacts

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Carol Bendall

Role: primary

+61 7 3176 1499

Jennifer Cranefield, RN

Role: primary

+61 8 7074 2900

Amy McDonald, RN

Role: primary

+61 3 9342 4424

References

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Di G, Vazquez-Reyes S, Diaz B, Pena-Martinez C, Garcia-Culebras A, Cuartero MI, Moraga A, Pradillo JM, Esposito E, Lo EH, Moro MA, Lizasoain I. Daytime DNase-I Administration Protects Mice From Ischemic Stroke Without Inducing Bleeding or tPA-Induced Hemorrhagic Transformation, Even With Aspirin Pretreatment. Stroke. 2025 Feb;56(2):527-532. doi: 10.1161/STROKEAHA.124.049961. Epub 2025 Jan 27.

Reference Type DERIVED
PMID: 39869712 (View on PubMed)

Other Identifiers

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MBC2101

Identifier Type: -

Identifier Source: org_study_id

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