Clinical trial NCT05203224: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ischemic Stroke
Keywords: thrombolysis
thrombolytic
endovascular thrombectomy
tenecteplase
dornase alfa
DNase
Lead sponsor: University of Melbourne
Sponsor class: OTHER
First posted: 2022-01-24
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Bayesian Optimised Phase 2 dose-finding umbrella trial
Primary purpose: TREATMENT

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 (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.


Eligibility 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

Primary outcomes:
measure: Proportion of patients with substantial angiographic reperfusion or absence of retrievable intracranial thrombus at initial angiogram without symptomatic intracerebral hemorrhage
timeFrame: 24 hours post-treatment
Secondary outcomes:
Other outcomes:
measure: modified Rankin Scale (mRS) at 3 months
timeFrame: 3 months post stroke
measure: modified Rankin Scale (mRS) 0-1 or no change from baseline at 3 months
timeFrame: 3 months post stroke
measure: modified Rankin Scale (mRS) 0-2 or no change from baseline at 3 months
timeFrame: 3 months post stroke
measure: Proportion of patients with 8 point reduction in NIHSS or reaching 0-1 at 3 days (early neurological improvement)
timeFrame: 3 days post stroke
measure: Proportion of patients with near-complete reperfusion (eTICI 2c/3) at conclusion of the endovascular procedure
timeFrame: day 0 (end of endovascular thrombectomy)
measure: Symptomatic intracranial hemorrhage (SICH)
timeFrame: 36 hours post treatment
measure: Death due to any cause
timeFrame: up to 3 months post stroke
Locations:
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: University of Melbourne
name: Bruce CV Campbell, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: