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

Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05203224
• Other study ID #: MBC2101
• Status: Recruiting
• Phase: Phase 2
• Start date: February 18, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2022
• Source: University of Melbourne
• Contact: Bruce CV Campbell, MBBS PhD
• Phone: 0393427000
• Email: bruce.campbell[@]mh.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Dornase Alfa
Intravenous Dornase alfa

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Melbourne Hospital	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
University of Melbourne

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	modified Rankin Scale (mRS) at 3 months	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)	3 months post stroke
Other	modified Rankin Scale (mRS) 0-1 or no change from baseline at 3 months	versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score	3 months post stroke
Other	modified Rankin Scale (mRS) 0-2 or no change from baseline at 3 months	versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score	3 months post stroke
Other	Proportion of patients with 8 point reduction in NIHSS or reaching 0-1 at 3 days (early neurological improvement)	versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS score	3 days post stroke
Other	Proportion of patients with near-complete reperfusion (eTICI 2c/3) at conclusion of the endovascular procedure	versus EXTEND-IA TNK I & II historical control	day 0 (end of endovascular thrombectomy)
Other	Symptomatic intracranial hemorrhage (SICH)	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"	36 hours post treatment
Other	Death due to any cause	versus EXTEND-IA TNK I & II historical control, adjusted for age and baseline NIHSS	up to 3 months post stroke
Primary	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.	24 hours post-treatment