Improving Early Reperfusion With Adjuvant Dornase Alfa in Large Vessel Ischemic Stroke (EXTEND-IA DNase)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 6
- 主要终点
- Proportion of patients with substantial angiographic reperfusion or absence of retrievable intracranial thrombus at initial angiogram without symptomatic intracerebral hemorrhage
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No blinding given single arm study but Independent core laboratory adjudication of the primary outcome, mRS (secondary outcome) performed by central assessor.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Dornase Alfa (Drug)
结局指标
主要结局
Proportion of patients with substantial angiographic reperfusion or absence of retrievable intracranial thrombus at initial angiogram without symptomatic intracerebral hemorrhage
时间窗: 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.
次要结局
未报告次要终点