Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke (EXTEND-AGNES TNK)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 462
- 试验地点
- 20
- 主要终点
- Early Neurological Improvement (Phase 2b)
研究概览
简要总结
Multicentre, prospective, Multi-arm Multi-stage (MAMS) seamless phase 2b/3 interventional randomized placebo-controlled double-blinded parallel-assignment (2 arms with 1:1 randomization) efficacy and safety trial to test intra-arterial tenecteplase at the completion of thrombectomy versus best practice in participants with anterior circulation LVO receiving mechanical thrombectomy within 24 hours of symptoms onset.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes 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
- •Adult participants (age≥18 years) presenting with ischemic stroke with arterial LVO on CT/MR Angiogram of the intracranial internal carotid or middle cerebral artery (MCA) first segment (M1) or proximal second segment (M2) committed to thrombectomy using standard criteria within 24 hours of onset:
- •For 0-6 hours of symptom onset: Presence of arterial occlusion as defined above and ASPECTS≥3 on NCCT
- •For 6-24 hours of symptom onset: Additional imaging criteria on CTP or MRI perfusion of core volume <100ml.
- •Qualifying CT/MR within 4hrs of randomisation (repeat CT for transferred participants required if >4hr)
- •Pre-stroke Modified Rankin Scale (mRS) score of ≤2 (mild pre-existing disability permitted)
- •Local legal requirements for consent have been satisfied.
排除标准
- •Intracranial hemorrhage identified by CT or MRI
- •ASPECTS 0-2 on NCCT
- •CTP or MRI perfusion ischemic core volume >100ml if presenting within 6-24 hours from symptoms onset
- •Anticipated endovascular stenting required for intracranial or extracranial atherosclerotic stenosis/occlusion.
- •More than six retrieval attempts in the same vessel
- •Alteplase being infused within 30 minutes (~5x half-life) of anticipated trial drug administration
- •Contraindication to imaging with contrast agents
- •Any condition (eg.mid-arterial phase early venous filling) that in the judgment of investigators could impose hazards if study therapy is initiated
- •Pregnant women.
- •Current participation in another intervention research study that includes experimental interventions beyond standard-of-care.
- •Anticoagulation. INR ≤1.7 if on warfarin, and dabigatran reversal by idarucizumab are permitted.
- •Other standard contraindications to thrombolysis apart from time window.
- •Known terminal illness such that the participants would not be expected to survive a year.
- •Planned withdrawal of care or comfort care measures.
研究组 & 干预措施
Placebo
Intra-arterial bolus of placebo (0.9% Sodium Chloride solution) representing standard of care (no intra-arterial thrombolytic treatment).
干预措施: Placebo (Drug)
Intra-arterial tenecteplase injection at the completion of thrombectomy
intra-arterial tenecteplase (0.062mg/kg, maximum 6.25mg) administered as a bolus at the completion of thrombectomy through a microcatheter at the site of the initial-but-now-retrieved intracranial occlusion or in direct contact with the residual thrombus
干预措施: Intra-arterial tenecteplase injection at the completion of thrombectomy (Drug)
结局指标
主要结局
Early Neurological Improvement (Phase 2b)
时间窗: 24-36 hours from time of randomisation
Proportion of participants with Early Neurological Improvement (ENI) defined as NIHSS reduction\>4
Functional independence (Phase 3)
时间窗: 3 months
Proportion of participants with Modified Rankin Scale (mRS) 0-2 (functional independence)
次要结局
- All cause mortality(3 months)
- Quality of life assessment on EQ-5D(3 months)
- Infarct growth(24 hours)
- Functional improvement(3 months)
- No-reflow(24 hours)
- Symptomatic Intracerebral Hemorrhage(36 hours)