Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke: A Phase IIa Randomized Clinical Trial.

Autor: Song H; Department of Neurology, Xuanwu Hospital, Capital Medicine University, 45 Chang Chun St, Beijing, 100053, China., Wang Y; Department of Neurology, Xuanwu Hospital, Capital Medicine University, 45 Chang Chun St, Beijing, 100053, China., Ma Q; Department of Neurology, Xuanwu Hospital, Capital Medicine University, 45 Chang Chun St, Beijing, 100053, China., Chen H; Department of Neurology, The General Hospital of Shenyang Military, Shenyang, Liaoning, China., Liu B; Department of Neurology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China., Yang Y; Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin, China., Zhu J; Department of Neurology, Halison International Peace Hospital, Hengshui, Hebei, China., Zhao S; Department of Neurology, The Affiliated Hospital of Inner Mogolia Medical University, Huhhot, Inner Mogolia, China., Jin X; Department of Neurology, TaiZhou Hospital of Zhejiang Province, Taizhou, Zhejiang, China., Li Y; Department of Neurology, Tangshan Worker's Hospital, Tangshan, Hebei, China., Wang Y; Department of Neurology, The First Hospital of Hebei University, Shijiazhuang, Hebei, China., Zhu R; Department of Neurology, Inner Mongolia People's Hospital, Huhhot, Inner Mogolia, China., Zhao L; Department of Neurology, The Second People's Hospital of Huai'an, Huai'an, Jiangsu, China., Liu J; Department of Neurology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Ma Q; Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China., Lin Y; Department of Neurology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China., Tian X; Department of Neurology, Huai'an First People's Hospital, Huai'an, Jiangsu, China., Zhang Q; Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China., Zhou W; Department of Neurology, China Meitan General Hospital, Beijing, China., Zhang Y; Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China., Zhou J; Department of Neurology, Chongqing Sanxia Center Hospital, Chongqing, China., Li Y; Department of Neurology, Shenyang 463 Hospital, Shenyang, Liaoning, China., Song Z; Department of Neurology, The Third Xiangya Hospital of General South University, Changsha, Hunan, China., Feng W; Department of Neurology, Duke University School of Medicine, Durham, NC, USA., Liu R; Department of Clinical Medicine, Tasly Biopharmaceuticals Co., Ltd, Tianjin, China., Ji X; Department of Neurosurgery, Xuanwu Hospital, Capital Medicine University, 45 Chang Chun St, Beijing, 100053, China. jixm@ccmu.edu.cn., Wang Y; Department of Neurology, Xuanwu Hospital, Capital Medicine University, 45 Chang Chun St, Beijing, 100053, China. doctorwangyuping@163.com.
Jazyk: angličtina
Zdroj: Translational stroke research [Transl Stroke Res] 2022 Dec; Vol. 13 (6), pp. 995-1004. Date of Electronic Publication: 2022 May 03.
DOI: 10.1007/s12975-022-01012-9
Abstrakt: Recombinant human prourokinase (rhPro-UK) is a novel thrombolytic that has been approved to treat patients with acute myocardial infarction. However, the safety and efficacy of intravenous rhPro-UK in patients with acute ischemic stroke (AIS) has not been well established. We aimed to investigate the safety and preliminary efficacy of rhPro-UK in patients with AIS in a multi-center phase IIa trial setting. One hundred nineteen patients within 4.5 h of AIS onset were enrolled in this randomized, open-label, 23-center phase IIa clinical trial. Patients were randomly assigned to 35 mg (n = 40) or 50 mg (n = 39) intravenous rhPro-UK or 0.9 mg/kg recombinant tissue plasminogen activator (r-tPA; n = 40). The primary endpoint was functional independence defined as a modified Rankin scale (mRS) score of 0 or 1 at 90 days. The secondary outcome was early neurological improvement defined as a reduction of ≥ 4 points on the National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 h after drug administration. Safety endpoints included death due to any cause, symptomatic intracerebral hemorrhage (sICH), and other serious adverse events (SAEs). The proportion of patients with an mRS score of ≤ 1 at 90 days did not differ significantly among three groups (35 mg rhPro-UK: 55.56% vs. 50 mg rhPro-UK: 57.89% vs. vs. r-tPA: 52.63%; P = 0.92). The rates of treatment response, referring to early neurological improvement, were similar among these three groups (36.11% vs. 31.58% vs. 28.95%, respectively; P = 0.85). There was no difference in mortality at 90 days or in the rate of other SAEs among the three groups. One patient in the 50 mg rhPro-UK group suffered sICH. While neither the primary efficacy outcomes nor safety profile differed significantly among the low, high rhPro-UK and control groups, it is a logical step to further test the low-dose rhPro-UK group versus the control group in a well-powered phase III study.Trial Registration: http://www.chictr.org.cn . Identifier: ChiCTR1800016519. Date of registration: June 6 2018.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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