{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:23:45Z","timestamp":1791901425561,"version":"4.3.4"},"reference-count":23,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n 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).<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the efficacy and safety of rhPro-UK thrombolysis within 4.5 hours of symptom onset in patients with AIS.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Eligible patients were randomly assigned (1:1) to receive intravenous rhPro-UK or alteplase.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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, \u22126.52 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 (\n P<\/jats:italic>\n \u2009&amp;gt;\u2009.99). 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%]) (\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). By 90 days, 5 thrombolysis-related deaths each had occurred in the rhPro-UK group (1.5%) and alteplase group (1.5%) (\n P<\/jats:italic>\n \u2009&amp;gt;\u2009.99).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03541668<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.25415","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T11:42:10Z","timestamp":1690285330000},"page":"e2325415","source":"Crossref","is-referenced-by-count":56,"title":["Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset"],"prefix":"10.1001","volume":"6","author":[{"given":"Haiqing","family":"Song","sequence":"first","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medicine University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medicine University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medicine University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuwei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Tasly Biopharmaceuticals Co, Ltd, Tianjin, 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