EXTEND-IA TNK: Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial Using Intravenous Tenecteplase Part 2
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 28
- 主要终点
- mTICI
研究概览
简要总结
Patients presenting to the emergency department with acute ischemic stroke, who are eligible for standard intravenous thrombolysis within 4.5 hours of stroke onset will be assessed for major vessel occlusion to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised 50:50 using central computerised allocation to either 0.4mg/kg or 0.25mg/kg intravenous tenecteplase before all participants undergo endovascular thrombectomy. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.
详细描述
The study will be a multicentre, prospective, randomized, open- label, blinded endpoint (PROBE), controlled phase 2 trial (2 arm with 1:1 randomization) in ischemic stroke patients.
Randomized patients will first be stratified by both the setting of treatment: metropolitan hospital vs regional hospital (>1 hour transfer to endovascular centre) vs mobile stroke unit; and by site of baseline arterial occlusion: Intracranial internal carotid artery (ICA) and Basilar artery versus Middle cerebral artery (MCA - M1 and M2); overall resulting in six strata.
Imaging is performed with CT or MR (magnetic resonance) acutely as part of standard care with imaging follow-up at 18-30 hours. The sequences and the parameters used follow the STIR (Stroke Imaging Research) roadmap guidelines, but imaging takes place acutely and at 18- 30hrs only, as previously validated.
The sample size estimation was based on the proportion of pre-endovascular reperfusion observed in the 0.25mg/kg group from Part 1 of EXTEND-IA TNK (22%). An estimated total sample size of 188 patients (with 94 patients in each of treatment and control arms) yielded 80% power to detect a significant difference of 20% in strata-weighted angiographic reperfusion (mTICI 2b/3) at initial angiogram (22% in 0.25mg/kg vs 42% in 0.4mg/kg arm) at two-sided statistical significance threshold of p=0.05 for superiority. Adaptive increase in sample size will be performed if the result of interim analysis using data from the first 150 patients is promising, as per the methodology of Mehta and Pocock.
During the trial, blinded analysis of operational characteristics revealed a 20% reduction in the time from thrombolysis to arterial access versus part 1 due to improved workflow (In the first 150 patients in part 2 median 37min [IQR 19-54] versus 46min [IQR 28-63] in part 1). This directly impacts the time for thrombolysis to have an effect. A 20% reduction in the hypothesized rate of reperfusion at initial angiogram (18% vs 33%) would require 145 patients per group. Allowing for potential further improvements in workflow the sample size re-estimation was postponed from 150 to 240 patients with a revised minimum sample of 300 patients. Adaptive increase in sample size will be performed if the result of interim analysis using data from the first 240 patients is promising, as per the methodology of Mehta and Pocock. The maximum sample size is capped at 656 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)
盲法说明
Blinded core laboratory adjudication of the primary outcome. NIHSS and mRS (secondary outcomes) performed by blinded 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 thrombolysis within 4.5 hours of stroke onset
- •Patient's age is ≥18 years
- •Arterial occlusion on CTA (computed tomography angiography) or MRA (Magnetic Resonance Angiography) 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
- •Contra indication 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 women
研究组 & 干预措施
Assigned Interventions
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over ~10 seconds).
干预措施: Tenecteplase (Drug)
Tenecteplase
Patients will receive intravenous tenecteplase (0.4mg/kg, maximum 40mg, administered as a bolus over ~10 seconds).
干预措施: Tenecteplase (Drug)
结局指标
主要结局
mTICI
时间窗: Initial angiogram (day 0)
Proportion of patients with substantial angiographic reperfusion (mTICI) score of 2b/3 (restoration of blood flow to \>50% of the affected arterial territory) or absence of retrievable thrombus at initial angiogram.
次要结局
- Death(Up to 3 months post stroke)
- Modified Rankin Scale (mRS)(at 3 months post stroke)
- National Institutes of Health Stroke Scale (NIHSS)(Initial angiogram (day 0))
- Symptomatic intracranial haemorrhage (SICH)(Within 36 hours post treatment)
- Angiographic reperfusion(Up to 24 hours post treatment)