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

Primary Purpose

Ischemic Stroke

Status

Recruiting

Phase

Phase 2

Locations

Australia

Study Type

Interventional

Intervention

Dornase Alfa

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring thrombolysis, thrombolytic, endovascular thrombectomy, tenecteplase, dornase alfa, DNase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Princess Alexandra HospitalRecruiting
Royal Adelaide Hospital
Royal Melbourne HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intravenous Dornase alfa (DNase)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT05203224

First Posted

January 10, 2022

Last Updated

May 22, 2022

Sponsor

University of Melbourne

1. Study Identification

Unique Protocol Identification Number

NCT05203224

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 18, 2022 (Actual)

Primary Completion Date

September 30, 2025 (Anticipated)

Study Completion Date

December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Melbourne

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Stroke

Keywords

thrombolysis, thrombolytic, endovascular thrombectomy, tenecteplase, dornase alfa, DNase

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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.

Allocation

N/A

Enrollment

300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intravenous Dornase alfa (DNase)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Dornase Alfa

Other Intervention Name(s)

DNase, Pulmozyme

Intervention Description

Intravenous Dornase alfa

Primary Outcome Measure Information:

Title

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

Description

Time Frame

24 hours post-treatment

Other Pre-specified Outcome Measures:

Title

modified Rankin Scale (mRS) at 3 months

Description

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)

Time Frame

3 months post stroke

Title

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

Description

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

Time Frame

3 months post stroke

Title

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

Description

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

Time Frame

3 months post stroke

Title

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

Description

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

Time Frame

3 days post stroke

Title

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

Description

versus EXTEND-IA TNK I & II historical control

Time Frame

day 0 (end of endovascular thrombectomy)

Title

Symptomatic intracranial hemorrhage (SICH)

Description

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"

Time Frame

36 hours post treatment

Title

Death due to any cause

Description

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

Time Frame

up to 3 months post stroke

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Bruce CV Campbell, MBBS PhD

Phone

0393427000

bruce.campbell@mh.org.au

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bruce CV Campbell, MBBS PhD

Organizational Affiliation

University of Melbourne

Official's Role

Principal Investigator

Facility Information:

Facility Name

Princess Alexandra Hospital

City

Brisbane

State/Province

Queensland

ZIP/Postal Code

4102

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Carol Bendall

Phone

+61 7 3176 1499

carol.bendall@health.qld.gov.au

First Name & Middle Initial & Last Name & Degree

Michael Devlin, MBBS

Facility Name

Royal Adelaide Hospital

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jennifer Cranefield, RN

Phone

+61 8 7074 2900

jennifer.cranefield@sa.gov.au

First Name & Middle Initial & Last Name & Degree

Timothy Kleinig, MBBS PhD

Facility Name

Royal Melbourne Hospital

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3050

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amy McDonald, RN

Phone

+61 3 9342 4424

amy.mcdonald@mh.org.au

First Name & Middle Initial & Last Name & Degree

Bruce Campbell, MBBS PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing Time Frame

2 years after the publication of the primary manuscript

IPD Sharing Access Criteria

Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA steering committee.

Learn more about this trial

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

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