Ahmed Niaz, Hermansson Karin, Bluhmki Erich, Danays Thierry, Nunes Ana Paiva, Kenton Anthony, Lakshmanan Sekaran, Toni Danilo, Mikulik Robert, Ford Gary A, Lees Kennedy R, Wahlgren Nils
Department of Clinical Neuroscience, Karolinska Institutet and Department of Neurology Karolinska University Hospital, Stockholm, Sweden.
Boehringer Ingelheim Medical Department, Boehringer Ingelheim AB, Stockholm, Sweden.
Eur Stroke J. 2016 Sep;1(3):213-221. doi: 10.1177/2396987316661890. Epub 2016 Jul 29.
The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3-4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice.
Inclusion of at least 1000 patients treated within 3-4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3-4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0-2, favourable outcome (mRS 0-1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS.
4157 patients from 81 centres in 12 EU countries were entered prospectively ( = 1118 in the 3-4.5 h, = 3039 in the 0-3 h time window) and 3454 retrospective patients in the 0-3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3-4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3-4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50).
Main weakness is the observational design of the study.
This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke.
SITS-UTMOST（急性缺血性卒中溶栓治疗在延长时间窗的安全实施监测研究）是一项基于注册登记的前瞻性研究，旨在评估急性缺血性卒中患者在延长时间窗（3 - 4.5小时）内使用静脉注射阿替普酶的情况，以评价延长时间窗获批对常规临床实践的影响。
计划纳入至少1000例根据许可标准在3 - 4.5小时内接受治疗并积极登记在SITS国际卒中溶栓注册登记中的患者。前瞻性数据收集于2012年5月2日开始，2014年11月2日结束。确定了2012年5月前两年的历史队列。在前瞻性队列中，对比了3小时内与3 - 4.5小时内接受治疗的患者的临床管理及结局，以及在3小时时间窗内历史队列与前瞻性队列的情况。结局指标包括功能独立性（改良Rankin量表，mRS）0 - 2分、良好结局（mRS 0 - 1分）、3个月时死亡以及根据SITS标准的症状性颅内出血（SICH）。
来自12个欧盟国家81个中心的4157例患者被前瞻性纳入研究（3 - 4.5小时组1118例，0 - 3小时时间窗组3039例），另有3454例0 - 3小时时间窗的回顾性患者符合上市批准条件。在前瞻性队列中，3 - 4.5小时组从到达至治疗的中位时间长于3小时组（79分钟对55分钟）。在3小时时间窗内，前瞻性队列患者的治疗延迟短于历史队列患者（55分钟对63分钟）。在3 - 4.5小时组与3小时前瞻性队列之间，报告的SICH百分比（1.6%对1.7%）、死亡（11.6%对11.1%）、3个月时的功能独立性（66%对65%）或良好结局（51%对50%）方面均无显著差异。
主要不足在于该研究为观察性设计。
本研究未发现将阿替普酶治疗的获批时间窗延长至4.5小时对治疗延迟或结局有负面影响。
