Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial
机构：[1]Department of Neurology, Xuanwu Hospital, Capital Medicine University, Beijing, China.神经科系统神经内科首都医科大学宣武医院[2]Department of Neurology, Duke University School of Medicine, Durham, North Carolina.[3]Department of Clinical Medicine, Tasly Biopharmaceuticals Co, Ltd, Tianjin, China.[4]Department of Neurology, First Bethune Hospital of Jilin University, Changchun, Jilin, China.[5]Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.[6]Department of Neurology, Harrison International Peace Hospital, Hengshui, Hebei, China.[7]Department of Neurology, General Hospital Northern Theater Command, Shenyang, Liaoning, China.[8]Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Huhhot, Inner Mogolia, China.[9]Department of Neurology, Second People's Hospital of Huai'an, Huai'an, Jiangsu, China.[10]Department of Neurology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.[11]Department of Neurology, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China.内蒙古科技大学包头医学院[12]Department of Neurology, Affiliated Hospital of Inner Mongolia Medical University, Huhhot, Inner Mogolia, China.
Recombinant human prourokinase (rhPro-UK) is a thrombolytic agent that has shown promising findings in a phase 2 clinical trial in patients with acute ischemic stroke (AIS).To evaluate the efficacy and safety of rhPro-UK thrombolysis within 4.5 hours of symptom onset in patients with AIS.This randomized, alteplase-controlled, open-label, phase 3 clinical trial was conducted from May 2018 to May 2020 at 35 medical centers in China. A total of 684 patients were screened and 674 patients were enrolled. Included patients were aged 18 to 80 years with a diagnosis of AIS and received treatment within 4.5 hours of stroke onset. Data were analyzed from June to October 2020.Eligible patients were randomly assigned (1:1) to receive intravenous rhPro-UK or alteplase.The primary objective was to assess whether rhPro-UK was noninferior to alteplase. The noninferiority margin was a between-group difference of less than 10%. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days.Among 663 patients in the modified intention-to-treat population (mean [SD] age, 61.00 [10.20] years; 161 females [24.3%]), there were 330 patients in the rhPro-UK group and 333 patients in the alteplase group. The median (IQR) baseline National Institutes of Health Stroke Scale score was 6.00 (5.00-9.00). There were 23 deaths, and 619 patients (93.4%) completed the 3-month follow-up. The primary outcome occurred in 215 patients (65.2%) in the rhPro-UK group and 214 patients (64.3%) in the alteplase group (risk difference, 0.89; 95.4% CI, -6.52 to 8.29). Symptomatic intracerebral hemorrhage occurred in 5 patients (1.5%) in the rhPro-UK group and 6 patients (1.8%) in the alteplase group (P > .99). Systemic bleeding within 90 days occurred more frequently in the alteplase group (141 patients [42.2%]) than the rhPro-UK group (85 patients [25.8%]) (P < .001). By 90 days, 5 thrombolysis-related deaths each had occurred in the rhPro-UK group (1.5%) and alteplase group (1.5%) (P > .99).This study found that intravenous rhPro-UK within 4.5 hours of AIS onset was noninferior to alteplase. The rhPro-UK group showed a similar rate of symptomatic ICH but fewer cases of systemic bleeding than the alteplase group.ClinicalTrials.gov Identifier: NCT03541668.
基金：
This study was sponsored by Tasly Biopharmaceuticals Co, Ltd, who reimbursed for both
alteplase and rhPro-UK.
第一作者机构：[1]Department of Neurology, Xuanwu Hospital, Capital Medicine University, Beijing, China.[*1]Department of Neurology, Xuanwu Hospital, Capital Medicine University, 45 Chang Chun St, Beijing 100053, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurology, Xuanwu Hospital, Capital Medicine University, Beijing, China.[*1]Department of Neurology, Xuanwu Hospital, Capital Medicine University, 45 Chang Chun St, Beijing 100053, China.
推荐引用方式(GB/T 7714)：
Song Haiqing,Wang Yuan,Ma Qingfeng,et al.Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial[J].JAMA NETWORK OPEN.2023,6(7):doi:10.1001/jamanetworkopen.2023.25415.
APA：
Song Haiqing,Wang Yuan,Ma Qingfeng,Feng Wuwei,Liu Rui...&Wang Yuping.(2023).Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial.JAMA NETWORK OPEN,6,(7)
MLA：
Song Haiqing,et al."Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial".JAMA NETWORK OPEN 6..7(2023)
医学