近日澳大利亚新南威尔士大学Fuqiang Fan小组比较了急性缺血性卒中患者静脉溶栓治疗后低强度监测与标准监测的安全性和有效性。该研究于2025年5月21日发表在《柳叶刀》杂志上。

普遍接受的监测急性缺血性脑卒中静脉溶栓患者的最佳实践方案是在20世纪90年代建立的。然而，该方案给护士带来了负担，扰乱了患者的睡眠，并且对症状性脑出血风险较低的患者可能不太相关。研究组旨在评估对低风险急性缺血性卒中患者实施低强度监测方案是否与标准高强度监测一样安全有效。

OPTIMISTmain是一项国际、务实、多中心、楔形步进、集群随机、对照、非劣效性、盲终点试验，在8个国家的医院（集群）进行。该研究的目的是测试低强度监测方案与标准方案在急性缺血性卒中连续成人患者中的非效性，这些患者在静脉溶栓开始后2小时内临床稳定，伴有轻度至中度神经功能损害（美国国立卫生研究院卒中量表评分为10分）。参与医院被随机分配到四个时期的三个实施顺序，按国家和预计参与人数分层，其中地点以阶梯式方式从标准监测（控制）切换到低强度监测（干预）。低强度监测方案包括每15分钟评估一次2小时的神经和生命体征，每2小时评估一次8小时（标准监测每30分钟评估一次6小时），每4小时评估一次（标准监测每1小时评估一次），直到溶栓后24小时。

主要结果是在90天内，由分组分配的研究人员在改良Rankin量表上以2分（表明一些残疾）到6分（死亡）的评分定义的功能结果不良的参与者的比例。意向治疗人群的风险比（RR）的非劣效性边际设定为1.15。采用广义线性混合模型进行分析，对聚类（医院地点）和时间（2021年4月起的6个月期间）进行调整，并对缺失的结果数据进行代入。该试验已在Clinicaltrials.gov （NCT03734640）和澳大利亚新西兰临床试验登记处（ACTRN 12619001556134p）注册并已完成。

在获得资格评估的181家医院中，120家医院同意加入试验，并在2021年4月28日至2024年9月30日期间随机分配；然而，一家医院退出，一家没有启动，四家没有招收任何患者。总体而言，114家医院的4922名参与者入组，其中2789名参与者被分配到低强度监测组，2133名参与者被分配到标准监测组。低强度组2552名受试者中809名（31.7%）和标准监测组1963名受试者中606名（30.9%）在90天的改良Rankin量表评分为2-6 （RR = 1.03，非劣效性= 0.057）。低强度组2783例患者中有5例（0.2%）出现症状性脑出血，标准监测组2122例患者中有8例（0.4%）出现症状性脑出血。发生严重不良事件的受试者人数在低强度监测组（2789人中的309人[11.1%]）和标准监测组（2133人中的240人[11.3%]）之间相似。

研究结果表明，OPTIMISTmain提供的微弱证据表明，在接受急性缺血性卒中溶栓治疗的轻度或中度神经功能损伤患者中，低强度监测不逊于标准监测。医院可以根据当地情况考虑将这种方法纳入中风服务。

附：英文原文

Title: Safety and efficacy of low-intensity versus standard monitoring following intravenous thrombolytic treatment in patients with acute ischaemic stroke (OPTIMISTmain): an international, pragmatic, stepped-wedge, cluster-randomised, controlled non-inferiority trial

Author: Craig S Anderson, Debbie Summers, Menglu Ouyang, Yi Sui, Brenda Johnson, Laurent Billot, Alejandra Malavera, Roland Faigle, Paula Muoz-Venturelli, Diana Day, Xiaoqiu Liu, Qiang Li, Lili Song, Thompson G Robinson, Francisca González, Francisca Urrutia-Goldsack, Michael Iacobelli, Michelle Montalbano, April Pruski, Candice Delcourt, Alice C Durham, Ahtasam Ebraimo, Ha Hong Van Ta, Pratiti Ghosh, Ann Leonhardt-Caprio, Huy Thang Nguyen, Mai Duy Ton, Stephen Jan, Hueiming Liu, Richard I Lindley, Antonio Arauz, Andrés Mercado, Wan Asyraf Wan Zaidi, Pooja Khatri, Xia Wang, Victor C Urrutia, Sheila Jala, Susan Day, Ying Hu, Aneeta Lal, Elizabeth OBrien, Michael Devlin, Carol Bendall, Christianna Nebauer, Duncan Maddox, Melissa Brooks, Timothy Kleinig, Jennifer Cranefield, Samantha McMahon, Roy Drew, Patrick McMullan, Joschka Straha, Donna Rowley, Helen Rodgers, Jessica Pyman, Rohan Grimley, Kylie Tastula, Xiaowen (Erin) Li, Stephen Walker, Alanah Bailey, Julia R Hennessey, Ken S Butcher, Darshan Ghia, Gillian Edmonds, Erin Casey, Lydia Ting, Jane Prosser, Krystle Franklin, Henry Ma, Thanh Phan, Jason Vuong, Berzenn Urbi, Rebecca Phair, Nino Jose, Andrew Shine, Susan Lane, Juliette Mai, F ORourke, Christine Fuller, Ravindra Urkude, Nerida Myers, Nicole Bradford, Yi Sui, Wei Bian, Xinze Guo, Yang Zhao, Yang Zhang, Xuchen Qi, Yanxing Zhang, Huan Tang, Xuan Fang, Min Zheng, Mingzong Yan, Yanyan Yin, Penglai Shi, Junmei Li, Junming Luo, Fuqiang Fan

Issue&Volume: 2025-05-21

Abstract:

Background

The universally accepted best practice protocol for monitoring patients who receive intravenous thrombolysis for acute ischaemic stroke was established in the 1990s. However, the protocol is burdensome for nurses, disrupts the sleep of patients, and is potentially less relevant in patients at low risk of symptomatic intracerebral haemorrhage. We aimed to assess whether implementing a low-intensity monitoring protocol would be as safe and effective as standard high-intensity monitoring for patients with acute ischaemic stroke at low risk.

Methods

OPTIMISTmain was an international, pragmatic, multicentre, stepped-wedge, cluster-randomised, controlled, non-inferiority, blinded-endpoint trial conducted at hospitals (clusters) in eight countries. It was designed to test the non-inferiority of a low-intensity monitoring protocol to a standard protocol among consecutive adults with acute ischaemic stroke who were clinically stable with mild to moderate neurological impairment (score <10 on the National Institutes of Health Stroke Scale) within 2 h of initiation of intravenous thrombolysis according to local guidelines. Participating hospitals were randomly allocated to three sequences of implementation across four periods, stratified by country and projected numbers of participants, in which sites switched from standard monitoring (control) to low-intensity monitoring (intervention) in a stepped manner. The low-intensity monitoring protocol included assessments of neurological and vital signs every 15 min for 2 h, every 2 h for 8 h (vs every 30 min for 6 h for standard monitoring), and every 4 h (vs every 1 h for standard monitoring) until 24 h after thrombolysis. The primary outcome was the proportion of participants with an unfavourable functional outcome defined by a score from 2 (indicating some disability) to 6 (death) on the modified Rankin Scale at 90 days, measured by research staff masked to group allocation. The non-inferiority margin was set at 1·15 for the risk ratio (RR) in the intention-to-treat population. A generalised linear mixed model was used for analysis with adjustments for cluster (hospital site) and time (6-month periods from April, 2021), and imputation of missing outcome data. This trial is registered at Clinicaltrials.gov (NCT03734640) and the Australian New Zealand Clinical Trial Registry (ACTRN 12619001556134p) and is completed.

Findings

Of 181 hospitals assessed for eligibility, 120 hospitals agreed to join the trial and were randomly allocated between April 28, 2021, and Sept 30, 2024; however, one hospital withdrew, one was not activated, and four did not enrol any patients. Overall, 4922 participants were enrolled at 114 hospitals, with 2789 participants assigned to the low-intensity monitoring group and 2133 to the standard monitoring group. 809 (31·7%) of 2552 participants in the low-intensity group and 606 (30·9%) of 1963 in the standard monitoring group had a modified Rankin Scale score of 2–6 at 90 days (RR 1·03 [95% CI 0·92–1·15], pnon-inferiority=0·057). Symptomatic intracerebral haemorrhage occurred in five (0·2%) of 2783 patients in the low-intensity group and eight (0·4%) of 2122 patients in the standard monitoring group. The numbers of participants with a serious adverse event were similar between the low-intensity monitoring group (309 [11·1%] of 2789) and the standard monitoring group (240 [11·3%] of 2133).

Interpretation

OPTIMISTmain provides weak evidence that low-intensity monitoring is non-inferior to standard monitoring in patients with a mild or moderate level of neurological impairment who receive thrombolysis treatment for acute ischaemic stroke. Hospitals could consider incorporating this approach into stroke services according to local circumstances.

DOI: 10.1016/S0140-6736(25)00549-5

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00549-5/abstract