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

Abstract

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.

• Authors: Haiqing Song, Yuan Wang, Qingfeng Ma, Huisheng Chen, Bo Liu, Yi Yang, Jianguo Zhu, Shigang Zhao, Xiaoping Jin, Yongqiu Li, Yanyong Wang, Runxiu Zhu, Liandong Zhao, Junyan Liu, Qilin Ma, Yongzhong Lin, Xiangyang Tian, Qing Zhang, Weidong Zhou, Yongbo Zhang, Jie Zhou, Yansong Li, Zhi Song, Wuwei Feng, Rui Liu, Xunming Ji, Yuping Wang
• Journal: Translational stroke research (Transl Stroke Res) Vol. 13 Issue 6 Pg. 995-1004 (Dec 2022) ISSN: 1868-601X [Electronic] United States
• PMID: 35505174 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Tissue Plasminogen Activator
• Fibrinolytic Agents

Topics

• Humans
• Tissue Plasminogen Activator (adverse effects)
• Ischemic Stroke
• Stroke (complications)
• Treatment Outcome
• Fibrinolytic Agents (adverse effects)
• Cerebral Hemorrhage (complications)
• Brain Ischemia (complications)
• Thrombolytic Therapy (adverse effects)