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
Department of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
Department of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Lancet Neurol. 2016 Nov;15(12):1228-1237. doi: 10.1016/S1474-4422(16)30234-4. Epub 2016 Oct 11.
Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage.
MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770.
Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7-22.6] vs eight [14·8%, 6·6-27·1], p=0·542), 7 day mortality (zero [0%, 0-8·4] vs one [1·9%, 0·1-9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1-12·6] vs five [9·3%, 3·1-20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1-12·6] vs zero [0%, 0-6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0-35·6] vs three [7·1%; 1·5-19·5]; p=0·051).
MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage.
National Institute of Neurological Disorders and Stroke, Genentech, and Codman.
根据试验结果，开颅手术并不能改善脑出血后的功能结局。微创导管引流联合溶栓清除血凝块是否安全且能实现良好的功能结局尚不清楚。我们研究了重组组织型纤溶酶原激活剂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是一项开放标签的2期试验，在美国、加拿大、英国和德国的26家医院进行。我们使用计算机生成的分配序列，以4为区组大小，将年龄在18 - 80岁、非创伤性（自发性）脑出血量为20 mL或更高的患者集中随机分配至标准医疗护理组或影像引导下的MIS联合阿替普酶组（每8小时0.3 mg或1.0 mg，最多9剂），通过手术抽吸清除血凝块，随后用阿替普酶冲洗血凝块。主要结局为所有安全性结局：30天死亡率、7天手术相关死亡率、72小时有症状出血以及30天脑感染。本试验已在ClinicalTrials.gov注册，注册号为NCT00224770。
在2006年2月2日至2013年4月8日期间，96例患者被随机分配并完成随访：MIS联合阿替普酶组54例（56%），标准医疗护理组42例（44%）。标准医疗护理组和MIS联合阿替普酶组的主要结局无差异：30天死亡率（4例[9.5%，95%CI 2.7 - 22.6] vs 8例[14.8%，6.6 - 27.1]，p = 0.542），7天死亡率（0例[0%，0 - 8.4] vs 1例[1.9%，0.1 - 9.9]，p = 0.562），有症状出血（1例[2.4%，0.1 - 12.6] vs 5例[9.3%，3.1 - 20.3]，p = 0.226），以及脑细菌感染（1例[2.4%，0.1 - 12.6] vs 0例[0%，0 - 6.6]，p = 0.438）。无症状出血在MIS联合阿替普酶组比标准医疗护理组更常见（12例[22.2%；95%CI 12.0 - 35.6] vs 3例[7.1%；1.5 - 19.5]；p = 0.051）。
MIS联合阿替普酶对脑出血患者似乎是安全的，但无症状出血增加是一个主要警示性发现。如果这些结果可重复，可能会将手术治疗作为脑出血的一种治疗策略。
美国国立神经疾病和中风研究所、基因泰克公司和科德曼公司。
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