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Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke
JAMA ( IF 63.1 ) Pub Date : 2020-04-07 , DOI: 10.1001/jama.2020.1511
Bruce C V Campbell 1, 2 , Peter J Mitchell 3 , Leonid Churilov 1, 2, 4 , Nawaf Yassi 1, 2, 5 , Timothy J Kleinig 6 , Richard J Dowling 3 , Bernard Yan 1, 3 , Steven J Bush 3 , Vincent Thijs 2, 7 , Rebecca Scroop 8 , Marion Simpson 7 , Mark Brooks 9 , Hamed Asadi 2, 9, 10 , Teddy Y Wu 11 , Darshan G Shah 12 , Tissa Wijeratne 13 , Henry Zhao 1 , Fana Alemseged 1 , Felix Ng 1 , Peter Bailey 14 , Henry Rice 15 , Laetitia de Villiers 15 , Helen M Dewey 16 , Philip M C Choi 16 , Helen Brown 12 , Kendal Redmond 17 , David Leggett 17 , John N Fink 11 , Wayne Collecutt 18 , Thomas Kraemer 19 , Martin Krause 20 , Dennis Cordato 21 , Deborah Field 22 , Henry Ma 23 , Bill O'Brien 24 , Benjamin Clissold 25 , Ferdinand Miteff 26 , Anna Clissold 27 , Geoffrey C Cloud 28 , Leslie E Bolitho 29 , Luke Bonavia 30 , Arup Bhattacharya 31 , Alistair Wright 32 , Abul Mamun 33 , Fintan O'Rourke 34 , John Worthington 35 , Andrew A Wong 36 , Christopher R Levi 37 , Christopher F Bladin 2, 16, 38 , Gagan Sharma 1 , Patricia M Desmond 3 , Mark W Parsons 1 , Geoffrey A Donnan 1 , Stephen M Davis 1 ,
Affiliation  

Importance Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, Setting, and Participants Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main Outcomes and Measures The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and Relevance Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial Registration ClinicalTrials.gov Identifier: NCT03340493.

中文翻译:

静脉注射替奈普酶剂量对大血管闭塞缺血性卒中患者取栓前脑再灌注的影响

重要性 与阿替普酶相比,替奈普酶静脉溶栓可改善缺血性卒中血管内血栓切除术前的再灌注。目的 确定 0.40 mg/kg 替奈普酶与 0.25 mg/kg 替奈普酶在大血管闭塞性缺血性卒中患者血管内血栓切除术前是否安全地改善再灌注。设计、设置和参与者 在澳大利亚的 27 家医院和新西兰的 1 家医院进行的随机临床试验,使用开放标签治疗和对放射学和临床结果进行盲法评估。患者于 2017 年 12 月至 2019 年 7 月入组,随访至 2019 年 10 月。因颅内颈内动脉、基底动脉或大脑中动脉闭塞而患有缺血性卒中的成年患者(N = 300)少于 4 人。症状发作后 5 小时使用标准的静脉溶栓资格标准。干预措施 血管内血栓切除术前以 0.40 mg/kg(最大,40 mg;n = 150)或 0.25 mg/kg(最大,25 mg;n = 150)的剂量给予开放标签的替奈普酶。主要结果和措施 主要结果是取栓前超过 50% 的受累缺血区域再灌注,由 2 位盲法神经放射科医师共同评估。预设的次要结局是第 90 天的残疾程度(改良 Rankin 量表 [mRS] 评分;范围,0-6);mRS 评分为 0 到 1(无残疾)或在 90 天时与基线相比没有变化;mRS 评分为 0 至 2(功能独立)或在 90 天时与基线相比没有变化;3 天后显着的神经系统改善;36 小时内出现症状性颅内出血;和全因死亡。结果 随机分组的所有 300 名患者(平均年龄 72.7 岁;141 名 [47%] 女性)均完成了试验。0.40 mg/kg 组的 150 人中有 29 人(19.3%)先前阻塞的血管区域再灌注超过 50%,而 0.25 mg/kg 组的 150 人中有 29 人(19.3%)(未调整的风险差异) , 0.0% [95% CI, -8.9% 至 -8.9%];调整后的风险比,1.03 [95% CI, 0.66-1.61];P = .89)。在 6 项次要结局中,0.40 mg/kg 和 0.25 mg/kg 组之间的 4 项功能结局中的任何一项以及全因死亡(26 [17%] vs 22 [15%];未调整)均无显着差异风险差异,2.7% [95% CI,-5.6% 至 11.0%])或有症状的颅内出血(7 [4.7%] vs 2 [1.3%];未经调整的风险差异,3.3% [95% CI,-0.5% 至7.2%])。结论和相关性 在大血管闭塞性缺血性卒中患者中,与 0.25 mg/kg 相比,0.40 mg/kg 剂量的替奈普酶在血管内取栓术前并未显着改善脑再灌注。研究结果表明,对于计划进行血管内血栓切除术的大血管闭塞性缺血性卒中患者,0.40-mg/kg 剂量的替奈普酶并不比 0.25-mg/kg 剂量具有优势。试验注册 ClinicalTrials.gov 标识符:NCT03340493。计划进行血管内血栓切除术的大血管闭塞性缺血性卒中患者 25 mg/kg 剂量。试验注册 ClinicalTrials.gov 标识符:NCT03340493。计划进行血管内血栓切除术的大血管闭塞性缺血性卒中患者 25 mg/kg 剂量。试验注册 ClinicalTrials.gov 标识符:NCT03340493。
更新日期:2020-04-07
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