Extending the Time Window for Tenecteplase by Effective RecanalizatioN of bAsilar Artery occLusion in Patients With POSTerior Circulation Stroke (POST-ETERNAL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 688
- 试验地点
- 32
- 主要终点
- Modified Rankin Scale (mRS) 0-1 or return to baseline mRS at 90 days
研究概览
简要总结
Patients presenting to the emergency department with an acute ischemic stroke due to basilar artery occlusion within 24 hours of stroke onset will be assessed to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised 50:50 using a central computerised allocation process to either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg) or tenecteplase 0.25mg/kg before undergoing mechanical thrombectomy as required at treating clinician's discretion. The trial is Multi-arm, Multi-stage, prospective, randomised, open-label, blinded endpoint (PROBE) design with seamless phase 2b/3 transition if the intermediate endpoint (recanalization without symptomatic intracerebral hemorrhage) is met in analysis of the first 202 patients. Adaptive sample size re-estimation (Mehta and Pocock) will be performed when 240 patients have completed 3 month follow-up (minimum sample size 320, maximum sample size 688).
详细描述
The study is a Multi-Arm Multi-Stage (MAMS), multiregional, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE), controlled seamless phase 2b/3 trial (2 arm with 1:1 randomisation) with adaptive sample size recalculation in patients with stroke due to basilar artery occlusion. Stage 1 will use the surrogate outcome of recanalization without symptomatic intracerebral hemorrhage (sICH) to establish whether proceeding to Stage 2 is warranted. If results in the first n= 202 patients meet success criteria, the trial will seamlessly convert to a phase 3 design using modified Rankin scale 0-1 at 3 months as the primary outcome (minimum n=320 with interim sample size re-estimation at n=240, maximum sample n=688) using the Mehta and Pocock conditional power method. Each regionally-based stratum will be pooled in the final analysis and analysed as a stratification by geographic region. Randomisation of patients within each stratum will be stratified by the investigator's intention to treat with mechanical thrombectomy (or not) and the investigator's intention to treat with alteplase intravenous thrombolysis should the patient be randomised to the control group (or not). Covariate adjusted minimum sufficient balance randomisation will then be applied to control for age, NIHSS and time from onset-to-randomisation (dichotomized as 0-6 hours vs 6-24 hours). The primary objective of the study is to test the hypothesis that the thrombolytic tenecteplase (TNK, 0.25mg/kg) ± mechanical thrombectomy administered within 24 hours after symptoms onset, is superior to current best practice (alteplase, rtPA, 0.9mg/kg or standard care/no lysis ± mechanical thrombectomy) in achieving excellent functional outcome (mRS 0-1) or return to the premorbid modified Rankin Scale at 90 days in patients with acute ischemic stroke due to basilar artery occlusion. Estimated study duration is 5 years. Patients will participate in the trial for 12 months.
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
- None (Investigator)
入排标准
- 年龄范围
- 18 Years 至 65+ years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients presenting with posterior circulation ischemic stroke symptoms due to partial or complete basilar artery occlusion within 24 hours from symptom onset (or clinical deterioration/coma) or the time the patient was last known to be well.
- •Patient's age is ≥18 years
- •Presence of basilar artery occlusion, proven by CT Angiography or MR Angiography. Basilar artery occlusion is defined as 'potentially retrievable' occlusion at the basilar artery. This can be a partial or complete occlusion.
- •Premorbid mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week).
- •Local legal requirements for consent have been satisfied.
排除标准
- •Intracerebral hemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging.
- •Posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) <7 on non-contrast CT, CT Angiography source images or DWI MRI.
- •Significant cerebellar mass effect or acute hydrocephalus.
- •Established frank hypodensity on non-contrast CT indicating subacute infarction.
- •Bilateral extensive brainstem ischemia.
- •Strong suspicion of underlying intracranial atherosclerotic disease (e.g diffuse arterial calcifications, basilar stenosis) or dissection which may require immediate neuro-interventional procedure with intracranial stenting and not benefit from intravenous thrombolysis at investigator's discretion.
- •Pre-stroke mRS of ≥4 (indicating moderate to severe previous disability).
- •Other standard contraindications to intravenous thrombolysis.
- •Contraindication to imaging with contrast agents.
- •Clinically evident pregnant women.
- •Current participation in another research drug treatment protocol.
- •Known terminal illness such that the patients would not be expected to survive a year.
- •Planned withdrawal of care or comfort care measures.
- •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.
研究组 & 干预措施
Intravenous tenecteplase (TNK)
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).
干预措施: Tenecteplase (Drug)
Standard Care (which may include intravenous Alteplase)
Patients will receive standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as a bolus and the remainder as an infusion over 1 hour).
干预措施: Standard Care (which may include intravenous Alteplase) (Drug)
结局指标
主要结局
Modified Rankin Scale (mRS) 0-1 or return to baseline mRS at 90 days
时间窗: 90 days
Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS 2-3) at 90 days
The proportion of patients with Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2-3) at 3 months.
The proportion of patients with Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2-3) at 3 months.
次要结局
- Modified Rankin Scale 0-2 or return to baseline mRS at 90 days(90 days)
- Modified Rankin Scale 0-3 or return to baseline mRS at 90 days(90 days)
- Ordinal analysis of the mRS at 90 days(90 days)
- Early clinical improvement(72 hours)
- Substantial reperfusion on initial digital subtraction angiography run prior to thrombectomy(Initial angiogram (day 0))
- Quality of Life assessment (EQ-5D) - at 90 days and 12 months(90 days and 12 months)
- Symptomatic intracerebral hemorrhage (sICH)(36 hours)
- All-cause mortality within 90 days(90 days)
- Modified Rankin Scale (mRS) 5-6 at 90 days(90 days)
- Proportion of patients with mRS 0-2 or return to baseline mRS at 3 months.
- Proportion of patients with mRS 0-3 or return to baseline mRS at 3 months.
- Ordinal analysis of the mRS, merging category 5-6, at 3 months.
- Proportion of patients achieving early clinical improvement (reduction in acute –72 hour NIHSS score of ≥8 or 72 hour NIHSS 0-1).
- Proportion of patients with complete occlusion at baseline who achieve eTICI 2b/3 [14] on initial digital subtraction angiography run prior to thrombectomy.
- Proportion of patients with sICH defined as parenchymal haemorrhage type 2 (PH2), subarachnoid haemorrhage, and/or intraventricular haemorrhage within 36 of treatment, combined with a neurological deterioration of ≥4 points on the NIHSS from baseline, or leading to death.
- Proportion of patients with mRS 5-6 at 90 days (severe disability or death).
- All-cause mortality within 90 days.
- Quality of Life assessment (EQ-5D) at 3 and 12 months.
研究者
Coordinating Investigator
Scientific
Centre Hospitalier Regional Universitaire De Tours