Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke,JAMA

当前位置： X-MOL 学术 › JAMA › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

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

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
Department of Radiology, the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia.
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Department of Neurology, Austin Hospital, Austin Health, Heidelberg, Victoria, Australia.
Department of Radiology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Department of Radiology, Austin Hospital, Austin Health, Heidelberg, Victoria, Australia.
School of Medicine, Faculty of Health, Deakin University, Victoria, Australia.
Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.
Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Melbourne Medical School, Department of Medicine and Neurology, The University of Melbourne and Western Health, Sunshine Hospital, St Albans Victoria, Australia.
Department of Neurology, Gold Coast University Hospital, Southport, Queensland, Australia.
Department of Radiology, Gold Coast University Hospital, Southport, Queensland, Australia.
Eastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Victoria, Australia.
Department of Radiology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Department of Radiology, Christchurch Hospital, Christchurch, New Zealand.
Department of Medicine, Ballarat Base Hospital, Ballarat, Victoria, Australia.
Department of Neurology, Royal North Shore Hospital and Kolling Institute, University of Sydney, St Leonards, New South Wales, Australia.
Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Australia.
Department of Neurology, Lyell McEwin Hospital, Adelaide, South Australia, Australia.
School of Clinical Sciences, Department of Medicine, Monash University, Clayton, Victoria, Australia.
Department of Neurology, Gosford Hospital, Gosford, New South Wales, Australia.
Department of Neurology, University Hospital Geelong, Deakin University, Geelong, Victoria, Australia.
Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia.
Department of Medicine, Southwest Healthcare, Warrnambool, Victoria, Australia.
Department of Neurology, Alfred Hospital, Prahran, Victoria, Australia.
Department of Medicine, Northeast Health, Wangaratta, Victoria, Australia.
Department of Medicine, Albury Base Hospital, Albury, New South Wales, Australia.
Department of Medicine, Goulburn Valley Health, Shepparton, Victoria, Australia.
Department of Medicine, Latrobe Regional Health, Traralgon, Victoria, Australia.
Department of Medicine, Campbelltown Hospital, Campbelltown, New South Wales, Australia.
Department of Aged Care and Rehabilitation, Bankstown-Lidcombe Hospital, Bankstown, New South Wales, Australia.
Department of Neurology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Department of Neurology, Royal Brisbane and Women's Hospital and the University of Queensland, Brisbane, Queensland, Australia.
Maridulu budyari gumal, The Sydney Partnership for Health Education Research & Enterprise (SPHERE), University of New South Wales, Sydney, Australia.
Victorian Stroke Telemedicine service, Ambulance Victoria, Melbourne, Victoria, Australia.

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

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文