Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial.
Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial.
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脑部出血疏散（Mistie）中微创手术加上高度的安全性和功效：一项随机，控制，开放标签，第2期试验。
DOI：
10.1016/s1474-4422(16)30234-4
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发表时间：
2016-11
期刊：
影响因子：
48
通讯作者：
Zuccarello, Mario
中科院分区：
文献类型：
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作者：
Hanley, Daniel F.;Thompson, Richard E.;Muschelli, John;Rosenblum, Michael;McBee, Nichol;Lane, Karen;Bistran-Hall, Amanda J.;Mayo, Steven W.;Keyl, Penelope;Gandhi, Dheeraj;Morgan, Tim C.;Ullman, Natalie;Mould, W. Andrew;Carhuapoma, J. Ricardo;Kase, Carlos;Ziai, Wendy;Thompson, Carol B.;Yenokyan, Gayane;Huang, Emily;Broaddus, William C.;Graham, R. Scott;Aldrich, E. Francois;Dodd, Robert;Wijman, Cristanne;Caron, Jean-Louis;Huang, Judy;Camarata, Paul;Mendelow, A. David;Gregson, Barbara;Janis, Scott;Vespa, Paul;Martin, Neil;Awad, Issam;Zuccarello, Mario
在临床试验中，开颅术并不能改善脑出血（ICH）后的预后。微创导管排空后溶栓是否安全，是否可以通过清除凝块获得良好的功能结局尚不清楚。我们研究了阿替普酶联合微创手术（MIS）治疗脑出血患者的安全性和有效性。MISTIE是一项国际、随机、开放标签研究，在美国、加拿大、英国和德国的26家医院进行。非创伤性（自发性）ICH ≥20 mL的患者（年龄18-80岁）在中心随机分配至医疗护理或图像引导MIS + rt-PA（0.3 mg或1.0 mg，每8小时一次，最多9次给药），通过手术抽吸清除凝块，然后进行阿替普酶凝块冲洗。主要疗效结局为症状发作后第180天评估的校正二分改良兰金量表（mRS）0-3 vs 4-6。通过意向治疗进行分析（ClinicalTrials.gov编号NCT 00224770）。2006年2月2日至2013年4月8日期间，96例受试者接受随机化并完成随访：54例接受治疗，42例接受医疗护理。主要安全性结局：死亡率、症状性出血、脑感染以及停止治疗，两组之间没有差异。无症状性复发在手术组中更常见（3例（7%）vs. 12例（22%），p= 0.05），差异为15.1%（95% CI：1.5%-28.6%）。估计的绝对效益，即，所有mRS 0-3的受试者中观察到的比例的未校正差异（33% vs 21%），分别为0.109 [95%CI：-0.088，0.294; p=0.26]和0.162 [95%CI：0.003，0.323; p=0.05]，调整研究组之间基线严重程度的潜在失衡后（主要疗效结局）。MIS+rt-PA似乎是安全的，180天时的功能结局明显更好。无症状出血增加是一个主要的警示发现。MISTIE试验结果如果可以复制，可以产生有意义的功能益处，增加手术治疗作为ICH的治疗策略。国家神经疾病和中风研究所，基因泰克和Codman。
Craniotomy, when evaluated in trials, does not improve outcome after intracerebral haemorrhage (ICH). Whether minimally invasive catheter evacuation followed by thrombolysis is safe and can achieve a good functional outcome by removing clot is unknown. We investigated safety and efficacy of alteplase with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. MISTIE was an international, randomized, open-label study and was done in 26 hospitals in the USA, Canada, the UK, and Germany. Patients (aged 18–80 years), with non-traumatic (spontaneous) ICH ≥20 mL were randomly allocated, centrally, to medical care or image-guided MIS plus rt-PA (0.3 mg or 1.0 mg every 8 hours for up to 9 doses) to remove clot using surgical aspiration followed with alteplase clot irrigation. The primary efficacy outcome was the adjusted dichotomized modified Rankin Scale (mRS) 0–3 vs 4–6 assessed at day 180 after symptom onset. Analysis was by intention to treat. (ClinicalTrials.gov number NCT00224770). Between February 2, 2006 and April 8, 2013, 96 subjects were randomized and completed follow-up: 54 received treatment and 42 medical care. Primary safety outcomes: mortality, symptomatic bleeding, brain infections, as well as withdrawal of care, did not differ between groups. Asymptomatic hemorrhages were more common in the surgical group (3 (7%) vs. 12 (22%) p= 0.05) producing a difference of 15.1% (95% CI: 1.5% to 28.6%). The estimated absolute benefit, i.e., the unadjusted difference in observed proportions of all subjects with mRS 0–3 (33% vs 21%) at 180 days comparing MISPA vs. medical control, is 0.109 [95%CI: −0.088, 0.294; p=0.26], and is 0.162 [95%CI: 0.003, 0.323; p=0.05] after adjustment for potential imbalances in baseline severity between study arms (primary efficacy outcome). MIS+rt-PA appears safe with an apparent advantage of better functional outcome at 180 days. Increased asymptomatic bleeding is a major cautionary finding. The MISTIE trial results, if replicable, could produce a meaningful functional benefit adding surgical management as a therapeutic strategy for ICH. National Institute of Neurologic Disorders and Stroke, Genentech, and Codman.