Thrombolysis with Recombinant Human Prourokinase 4.5–6 h After Acute Ischemic Stroke: A Phase IIa, Randomized, and Open-Label Multicenter Clinical Trial

作者：Haiqing Song, Yuan Wang, Yuan Wang, Qingfeng Ma, Huisheng Chen, Bo Liu, Yi Yang, Jianguo Zhu, Shigang Zhao, Xiaoping Jin, Yongqiu Li, Yanyong Wang, Yanyong Wang, Runxiu Zhu, Liandong Zhao, Junyan Liu, Wuwei Feng, Rui Liu, Xunming Ji, Yuping Wang, Yuping Wang · 发表于：CNS Drugs · 年份：2023 · DOI：10.1007/s40263-023-01051-2 · 被引用次数：14 · 研究领域：Acute Ischemic Stroke Management、Protease and Inhibitor Mechanisms、Blood Coagulation and Thrombosis Mechanisms

BACKGROUND: Ischemic stroke is a major cause of disability and death worldwide. A narrow therapeutic window profoundly constrained the utilization of alteplase. OBJECTIVES: To investigate therapeutic effects and safety of intravenous recombinant human prourokinase (rhPro-UK) in patients with acute ischemic stroke (AIS) in the 4.5-6 h therapeutic time windows. METHODS: We conducted a phase IIa, randomized, and open-label multicenter clinical trial. Between 4.5 and 6 h after the onset of AIS, patients were randomly administrated to receive intravenous rhPro-UK at a 50 mg or 35 mg dose. The primary endpoint was excellent functional outcome defined as modified Rankin scale (mRS) score of 1 or less at 90 days. The secondary outcome was the treatment response, which was based on an at least 4-point improvement from baseline National Institutes of Health stroke scale (NIHSS) score at 24 h after drug administration. Safety endpoints included death, symptomatic intracerebral hemorrhage (sICH), and other serious adverse events. RESULTS: We enrolled 80 patients in the 4.5-6 h therapeutic time windows at 17 medical centers in China from December 2016 to November 2017. A total of 39 patients were treated with 50 mg rhPro-UK, and 39 were treated with 35 mg rhPro-UK. Compared with the baseline, the NIHSS score at 24 h and days 7, 14, 30, and 90 was decreased significantly among patients treated with either rhPro-UK 50 mg or 35 mg. The mean reduction in the NIHSS from baseline to 90 days aft...