澳大利亚皇家墨尔本医院Bruce C. V. Campbell研究小组，分析了静脉注射不同剂量替奈普酶对大血管闭塞性缺血性中风患者血栓切除术前脑再灌注的影响。这一研究成果发表在2020年2月20日出版的国际学术期刊《美国医学会杂志》上。

与阿替普酶相比，替奈普酶静脉溶栓治疗可改善缺血性卒中患者血管内血栓切除术前的再灌注。

为了确定0.40 mg/kg的替奈普酶与0.25 mg/kg的替奈普酶相比，是否可安全改善大血管闭塞性缺血性卒中患者血管内血栓切除术前的再灌注，2017年12月至2019年7月，研究组在澳大利亚的27家医院和新西兰的1家医院进行了一项开放标签、放射学和临床结局盲法评估、随机临床试验。

研究组共招募了300例因颅内颈内动脉、基底层或大脑中动脉闭塞导致缺血性卒中症状发作的患者，均采用标准静脉溶栓治疗，平均年龄为72.7岁，47%为女性。将其按1：1随机分组，其中150例在血管内血栓切除术前静脉推注0.40 mg/kg的替奈普酶，150例推注0.25 mg/kg的替奈普酶。

治疗90天后，0.40 mg/kg组中有29人（19.3%）先前被阻塞的血管区域再灌注大于50%，0.25 mg/kg组中亦有29人（19.3%）。两组间其他6项次要结局、全因死亡、有症状颅内出血等均无显著差异。

总之，对于大血管闭塞性缺血性卒中的患者，采用0.40 mg/kg的替奈普酶，与0.25 mg/kg的替奈普酶相比，并不能显著改善血管内血栓切除术前的脑血管再灌注。

附：英文原文

Title: Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial

Author: Bruce C. V. Campbell, Peter J. Mitchell, Leonid Churilov, Nawaf Yassi, Timothy J. Kleinig, Richard J. Dowling, Bernard Yan, Steven J. Bush, Vincent Thijs, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Teddy Y. Wu, Darshan G. Shah, Tissa Wijeratne, Henry Zhao, Fana Alemseged, Felix Ng, Peter Bailey, Henry Rice, Laetitia de Villiers, Helen M. Dewey, Philip M. C. Choi, Helen Brown, Kendal Redmond, David Leggett, John N. Fink, Wayne Collecutt, Thomas Kraemer, Martin Krause, Dennis Cordato, Deborah Field, Henry Ma, Bill O’Brien, Benjamin Clissold, Ferdinand Miteff, Anna Clissold, Geoffrey C. Cloud, Leslie E. Bolitho, Luke Bonavia, Arup Bhattacharya, Alistair Wright, Abul Mamun, Fintan O’Rourke, John Worthington, Andrew A. Wong, Christopher R. Levi, Christopher F. Bladin, Gagan Sharma, Patricia M. Desmond, Mark W. Parsons, Geoffrey A. Donnan, Stephen M. Davis

Issue&Volume: 2020-02-20

Abstract: 

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.

DOI: 10.1001/jama.2020.1511

Source: https://jamanetwork.com/journals/jama/fullarticle/2761799