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卒中发生后9小时内灌注成像引导溶栓
Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke


Henry Ma ... 心脑血管疾病 • 2019.05.09
相关阅读
• 灌注成像可否延长静脉溶栓的时间窗 • 将卒中静脉溶栓的时间窗延长至4.5小时之后 • MRI引导下阿替普酶静脉给药治疗卒中——仍然卡在时间上 • 急性缺血性卒中的静脉溶栓治疗 • 缺血性卒中血栓切除术前使用替奈普酶和阿替普酶的比较

摘要


背景

急性缺血性卒中的静脉溶栓开始时间一般限制在症状发生后4.5小时以内。一些试验提示,对于影像学检查显示脑组织缺血但尚未梗死的患者,治疗时间窗可能可以延长。

 

方法

我们在自动灌注成像检测到脑部区域灌注不足但可挽救的缺血性卒中患者中,开展了一项多中心、随机、安慰剂对照试验。患者被随机分组,在卒中发生后4.5~9.0小时或者在卒中后醒来时(如果距离睡眠中点不到9小时),分别接受阿替普酶或安慰剂静脉给药。主要结局是90日时改良Rankin量表评分为0或1分,改良Rankin量表评分范围为0(无症状)~6(死亡)分。我们针对基线时的年龄和临床严重程度,对主要结局的危险比进行了校正。

 

结果

本试验原计划纳入310例患者,纳入225例患者后,之前一项试验发表的阳性结果致使本试验丧失临床均势,因此试验终止。总共113例患者被随机分配至阿替普酶组,112例被分配至安慰剂组。阿替普酶组40例患者(35.4%)和安慰剂组33例患者(29.5%)发生了主要结局(校正的危险比,1.44;95%置信区间[CI],1.01~2.06;P=0.04)。阿替普酶组7例患者(6.2%)和安慰剂组1例患者(0.9%)发生了有症状的脑内出血(校正的危险比,7.22;95% CI,0.97~53.5;P=0.05)。改良Rankin量表评分分布情况的二次有序分析表明,90日时的功能改善情况无显著组间差异。

 

结论

本试验表明,在脑组织可挽救的缺血性卒中患者中,与在卒中发生后4.5~9.0小时或者患者带着卒中症状醒来时使用安慰剂相比,使用阿替普酶使较高比例的患者无神经功能缺损或仅有轻微神经功能缺损。阿替普酶组有症状的脑出血病例高于安慰剂组(由澳大利亚国家健康与医学研究委员会[Australian National Health and Medical Research Council]等资助;EXTEND在ClinicalTrials.gov注册号为NCT00887328和NCT01580839)。





作者信息

Henry Ma, Ph.D., Bruce C.V. Campbell, Ph.D., Mark W. Parsons, Ph.D., Leonid Churilov, Ph.D., Christopher R. Levi, M.B., B.S., Chung Hsu, Ph.D., Timothy J. Kleinig, Ph.D., Tissa Wijeratne, M.D., Sami Curtze, Ph.D., Helen M. Dewey, Ph.D., Ferdinand Miteff, M.B., B.S., Chon-Haw Tsai, Ph.D., Jiunn-Tay Lee, M.D., Thanh G. Phan, Ph.D., Neil Mahant, Ph.D., Mu-Chien Sun, M.D., Martin Krause, M.D., Jonathan Sturm, Ph.D., Rohan Grimley, Ph.D., Chih-Hung Chen, M.D., Chaur-Jong Hu, M.D., Andrew A. Wong, Ph.D., Deborah Field, M.B., B.S., Yu Sun, M.D., P. Alan Barber, Ph.D., Arman Sabet, M.D., Jim Jannes, Ph.D., Jiann-Shing Jeng, M.D., Ph.D., Benjamin Clissold, Ph.D., Romesh Markus, Ph.D., Ching-Huang Lin, M.D., Li-Ming Lien, M.D., Christopher F. Bladin, M.D., Søren Christensen, Ph.D., Nawaf Yassi, Ph.D., Gagan Sharma, M.C.A., Andrew Bivard, Ph.D., Patricia M. Desmond, M.D., Bernard Yan, D.Med.Sci., Peter J. Mitchell, M.Med., Vincent Thijs, Ph.D., Leeanne Carey, Ph.D., Atte Meretoja, Ph.D., Stephen M. Davis, M.D., and Geoffrey A. Donnan, M.D. for the EXTEND Investigators*
From Florey Institute of Neuroscience and Mental Health (H.M., L. Churilov, N.Y., V.T., L. Carey, A.M., G.A.D.), the Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital (B.C.V.C., M.W.P., L. Churilov, S. Christensen, N.Y., G.S., A.B., B.Y., A.M., S.M.D., G.A.D.), and the Department of Radiology, Royal Melbourne Hospital (P.M.D., B.Y., P.J.M.), University of Melbourne, Parkville, the Department of Medicine, School of Clinical Science, Monash University, Clayton (H.M., T.G.P.), the Departments of Medicine and Neurology, Melbourne Medical School, University of Melbourne and Western Health, Sunshine Hospital, St. Albans (T.W.), the Department of Neurosciences, Eastern Health and Eastern Health Clinical School, Monash University, Box Hill (H.M.D., C.F.B.), the Department of Neurology, University Hospital Geelong, Deakin University, Geelong (B.C.), the Department of Neurology, Austin Hospital, Austin Health, Heidelberg (V.T.), and Occupational Therapy, School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora (L. Carey), VIC, the Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital (C.R.L., F.M.), University of Newcastle (J.S.), Newcastle, the Department of Neurology, Westmead Hospital (N.M.), the Department of Neurology, Royal North Shore Hospital and Kolling Institute, University of Sydney (M.K.), and the Department of Neurology, St. Vincent’s Hospital Sydney (R.M.), Sydney, and the Department of Neurology, Gosford Hospital, Gosford (J.S.), NSW, the Department of Neurology, Royal Adelaide Hospital (T.J.K., J.J.), the Department of Neurology, Lyell McEwin Hospital (D.F.), and the Department of Neurology, Queen Elizabeth Hospital (J.J.), Adelaide, SA, the Department of Medicine, Sunshine Coast University Hospital, Nambour (R.G.), the Department of Neurology, Royal Brisbane and Women’s Hospital and the University of Queensland, Brisbane (A.A.W.), and the Department of Neurology, Gold Coast University Hospital, Southport (A.S.), and Australia and Griffith University, Gold Coast (A.S.), QLD — all in Australia; the Graduate Institute of Clinical Medical Science (C.H.) and the School of Medicine (C.-H.T.), China Medical University, and the Department of Neurology, China Medical University Hospital (C.-H.T.), Taichung, the Department of Neurology, Tri-Service General Hospital, National Defense Medical Center (J.-T.L.), the Department of Neurology, Shuang Ho Hospital (C.-J.H.), the Department of Neurology, En Chu Kong Hospital (Y.S.), the Stroke Center and Department of Neurology, National Taiwan University Hospital (J.-S.J.), and the Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei Medical University College of Medicine (L.-M.L.), Taipei, the Stroke Center and Department of Neurology, Changhua Christian Hospital, Changhua (M.-C.S.), the Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan (C.-H.C.), and the Department of Neurology, Kaohsiung Veterans General Hospital, Kaohsiung (C.-H.L.) — all in Taiwan; the Department of Neurology, Helsinki University Hospital, Helsinki (S. Curtze, A.M.); the Department of Neurology, Auckland City Hospital, University of Auckland, Auckland, New Zealand (P.A.B.); and the Stanford Stroke Center, Stanford University, Stanford, CA (S. Christensen). Address reprint requests to Dr. Donnan at Florey Institute of Neuroscience and Mental Health, University of Melbourne, Royal Melbourne Hospital, 300 Grattan St., Parkville, VIC 3050, Australia, or at geoffrey.donnan@unimelb.edu.au. *A list of the investigators in the EXTEND trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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