Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke A Randomized Clinical Trial

被引：80

作者：

Wang, Anxin ^{[1
,2
]}

Jia, Baixue ^{[1
,2
]}

Zhang, Xuelei ^{[1
,2
,3
]}

Huo, Xiaochuan ^{[1
,2
]}

Chen, Jianhuang ^{[4
]}

Gui, Liqiang ^{[5
]}

Cai, Yefeng ^{[6
]}

Guo, Zaiyu ^{[7
]}

Han, Yuqing ^{[8
]}

Peng, Zhaolong ^{[9
]}

Jing, Ping ^{[10
]}

Chen, Yongjun ^{[11
]}

Liu, Yan ^{[12
]}

Yang, Yong ^{[13
]}

Wang, Fengyun ^{[14
]}

Sun, Zengqiang ^{[15
]}

Li, Tong ^{[16
]}

Sun, Hongxia ^{[17
]}

Yuan, Haicheng ^{[18
]}

Shao, Hongmin ^{[19
]}

Gao, Lianbo ^{[20
]}

Zhang, Peipei ^{[21
]}

Wang, Feng ^{[22
,29
]}

Cao, Xiangyang ^{[23
,24
]}

Shi, Wanchao ^{[25
]}

Li, Changmao ^{[26
]}

Yang, Jianwen ^{[27
]}

Zhang, Hong ^{[28
]}

Wang, Feng ^{[22
,29
]}

Deng, Jianzhong ^{[30
]}

Liu, Yanjie ^{[31
]}

Deng, Weisheng ^{[32
]}

Song, Cunfeng ^{[33
]}

Chen, Huisheng ^{[34
]}

He, Li ^{[35
]}

Zhao, Hongdong

Li, Xianfeng ^{[37
]}

Yang, Hong ^{[38
]}

Zhou, Zhiming ^{[36
,39
]}

Wang, Yilong ^{[1
,2
]}

Miao, Zhongrong ^{[1
,2
]}

机构：

[1] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China

[2] Capital Med Univ, Beijing Tiantan Hosp, China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China

[3] Capital Med Univ, Beijing Inst Brain Disorders, Ctr Stroke, Beijing, Peoples R China

[4] Liuyang Jili Hosp, Dept Neurol, Liuyang, Hunan, Peoples R China

[5] Langfang Changzheng Hosp, Dept Intervent Neuroradiol, Langfang, Hebei, Peoples R China

[6] Tradit Chinese Med Hosp Guangdong Prov, Dept Neurol, Dongguan, Guangdong, Peoples R China

[7] Tianjin TEDA Hosp, Dept Neurosurg, Tianjin, Peoples R China

[8] Tianjin Xiqing Hosp, Dept Neurol, Tianjin, Peoples R China

[9] Nanyang Nanshi Hosp, Dept Neurosurg, Nanyang, Henan, Peoples R China

[10] Cent Hosp Wuhan, Dept Neurol, Wuhan, Hubei, Peoples R China

[11] Univ South China, Dept Neurol, Nanhua Hosp, Huna, Peoples R China

[12] Jingjiang Peoples Hosp, Dept Neurol, Taizhou, Jiangsu, Peoples R China

[13] Jilin Qianwei Hosp, Dept Neurol, Changchun, Jilin, Peoples R China

[14] Liaocheng Brain Hosp, Dept Neurol, Liaocheng, Shandong, Peoples R China

[15] Zibo Municipal Hosp, Dept Neurol, Zibo, Shandong, Peoples R China

[16] Second Peoples Hosp Nanning, Dept Neurol, Nanning, Guangxi, Peoples R China

[17] Jilin Prov Peoples Hosp, Dept Neurol, Liaoyuan, Jilin, Peoples R China

[18] Qingdao Cent Hosp, Dept Neurol, Qingdao, Shandong, Peoples R China

[19] Tangshan Fengrun Dist Peoples Hosp, Dept Neurol, Tangshan, Peoples R China

[20] China Med Univ, Dept Neurol, Affiliated Hosp 4, Shenyang, Liaoning, Peoples R China

[21] Peoples Hosp Nanpi, Dept Neurol, Wuhan, Hubei, Peoples R China

[22] Nanjing Med Univ, Affiliated Wuxi Peoples Hosp, Dept Neurol, Nanjing, Peoples R China

[23] Xuzhou Med Univ, Affiliated Huaian Hosp, Xuzhou, Jiangsu, Peoples R China

[24] Second Peoples Hosp Huaian, Huaian, Jiangsu, Peoples R China

[25] Peking Univ, BinHai Hosp, Dept Neurosurg, Tianjin, Peoples R China

[26] Loudi Cent Hosp, Dept Neurol, Loudi, Hunan, Peoples R China

[27] Peoples Hosp Hunan Prov, Dept Intervent Neuroradiol, Changsha, Hunan, Peoples R China

[28] Fushun Min Bur Liaoning Hlth Ind Grp, Gen Hosp, Dept Neurol, Fushun, Liaoning, Peoples R China

[29] Shanghai Seventh Peoples Hosp, Dept Neurol, Shanghai, Peoples R China

[30] Anyang Dist Hosp, Dept Neurol, Anyang, Henan, Peoples R China

[31] Southern Med Univ, Shenzhen Hosp, Dept Neurol, Shenzhen, Peoples R China

[32] Meizhou Peoples Hosp, Dept Neurol, Meizhou, Guangdong, Peoples R China

[33] Liaocheng Third Peoples Hosp, Dept Intervent Neuroradiol, Liaocheng, Shandong, Peoples R China

[34] Gen Hosp Northern Theatre Command, Dept Neurol, Shenyang, Liaoning, Peoples R China

[35] Sichuan Univ, West China Hosp, Dept Neurol, Chengdu, Sichuan, Peoples R China

[36] Nanjing Med Univ, Nanjing Hosp 1, Dept Neurol, Nanjing, Jiangsu, Peoples R China

[37] First Peoples Hosp Nanning City, Dept Neurol, Nanning, Guangxi, Peoples R China

[38] Guangxi Med Univ, Affiliated Hosp 4, Dept Neurol, Nanning, Guangxi, Peoples R China

[39] Wannan Med Coll, Yijishan Hosp, Dept Neurol, Wuhu, Anhui, Peoples R China

来源：

JAMA NEUROLOGY | 2023年 / 80卷 / 08期

关键词：

HEALTH-CARE PROFESSIONALS; DOUBLE-BLIND; EARLY MANAGEMENT; 2018; GUIDELINES; DL-3-N-BUTYLPHTHALIDE; NXY-059;

D O I：

10.1001/jamaneurol.2023.1871

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Importance DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown.Objective To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment.Design, Setting, and Participants This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022.Interventions Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio.Main Outcomes and Measures The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity.Results Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group.Conclusions and Relevance Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo.

引用

页码：851 / 859

页数：9

共 38 条

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