A Phase 3, Multicenter, Prospective, Randomized, Open-label, Blinded-endpoint (PROBE) Controlled Trial of Tenecteplase Versus Standard Medical Treatment for Acute Ischemic Stroke Due to Anterior Circulation Large Vessel Occlusion With Perfusion Mismatch up to 24 Hours of Symptom Onset
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 516
- 试验地点
- 1
- 主要终点
- Excellent functional outcome
研究概览
简要总结
The trial is a phase 3, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) controlled design. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion within 4.5-24 hours from last known well (including wake-up stroke and unwitnessed stroke) will be randomized 1:1 to 0.25mg/kg intravenous tenecteplase or standard medical treatment.
详细描述
The study will be a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), controlled phase 3 trial (2 arms with 1:1 randomization) in ischemic stroke due to anterior circulation large vessel occlusion with perfusion mismatch up to 24 hours of symptom onset. The target mismatch profiles on CTP or MRI perfusion weighted imaging include ischemic core volume <70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL demonstrated by a certified automatic software. The minimum sample size is 516 patients.
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
- Single (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
- •Age ≥18 years old;
- •Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrolment; including wake-up stroke and unwitnessed stroke, onset time refers to "last-seen normal time";
- •Internal carotid artery, middle cerebral artery M1 or M2 occlusion confirmed by CTA/MRA, internal carotid artery, middle cerebral artery M1 or M2 being responsible for signs and symptoms of acute ischemic stroke;
- •Pre-stroke modified Rankin scale (mRS) score≤1;
- •Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive);
- •Neuroimaging: target mismatch profile on CTP or MRI+MR Perfusion (ischemic core volume <70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL;
- •Written informed consent from patients or their legally authorized representatives.
排除标准
- •Intended to proceed to endovascular treatment;
- •Allergy to tenecteplase;
- •Rapidly improving symptoms at the discretion of the investigator;
- •NIHSS consciousness score 1a >2, or epileptic seizure, hemiplegia after seizures ( Todd's palsy ) or other neurological/mental illness such that the patient is not able to cooperate or unwilling to cooperate;
- •Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg), despite blood pressure-lowering treatment;
- •Blood glucose <2.8 or >22.2 mmol/L (point of care glucose testing is acceptable );
- •Active internal bleeding or at high risk of bleeding, e.g., major surgery, trauma or gastrointestinal or urinary tract hemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days;
- •Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR >1.7 or prothrombin time >15 seconds; use of any direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours unless reversal of effect can be achieved with a reversal agent; any full dose heparin/heparinoid during the last 24 hours or with an elevated aPTT greater than the upper limit of normal;
- •Known defect of platelet function or platelet count below 100,000/mm3 (NB patients taking antiplatelet medication can be included);
- •Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial hemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm, arteriovenous malformation or giant aneurysm;
- •Any terminal illness such that the patient would not be expected to survive more than 1 year;
- •Unable to perform CTP or PWI;
- •Hypodensity in >1/3 MCA territory on non-contrast CT;
- •Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI;
- •Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion);
- •Pregnant women, nursing mothers, or reluctant to use effective contraceptive measures during the period of trial;
- •Unlikely to adhere to the trial protocol or follow-up;
- •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;
- •Participation in other interventional clinical trials within the previous 3 months.
研究组 & 干预措施
tenecteplase ( 0.25 mg/kg, Max 25 mg )
Tenecteplase (0.25 mg/kg) is given as a single, intravenous bolus (within 5-10 seconds) immediately upon randomization. Maximum dose 25mg.
干预措施: tenecteplase (0.25 mg/kg, Max 25 mg) (Drug)
standard medical treatment
Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone after randomization at the discretion of local investigators.
干预措施: standard medical treatment (Drug)
结局指标
主要结局
Excellent functional outcome
时间窗: 90 days
Proportion of excellent functional outcome defined as an mRS score ≤ 1 at 90 days
次要结局
- Clinical response rate at 72 hours(72 hours)
- Systemic bleeding(90 days)
- NIHSS change from baseline(7 days)
- Symptomatic intracranial hemorrhage(36 hours)
- Mortality(90 days)
- Favorable functional outcome(90 days)
- Ordinal distribution of mRS(90 days)
- The rate of improvement on reperfusion(24 hours)
- Adverse events ( AEs ) / serious adverse events ( SAEs )(90 days)
研究者
Yongjun Wang
professor
Beijing Tiantan Hospital