Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke : A Phase IIa Randomized Clinical Trial
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Translational stroke research - 13(2022), 6 vom: 03. Dez., Seite 995-1004 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Song, Haiqing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.10.2022 Date Revised 07.11.2022 published: Print-Electronic ChiCTR: ChiCTR1800016519 Citation Status MEDLINE |
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| doi: |
10.1007/s12975-022-01012-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM340338741 |
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| 245 | 1 | 0 | |a Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke |b A Phase IIa Randomized Clinical Trial |
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| 520 | |a © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase II | |
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| 650 | 4 | |a Acute ischemic stroke | |
| 650 | 4 | |a Early neurological improvement | |
| 650 | 4 | |a Efficacy | |
| 650 | 4 | |a Recombinant human prourokinase | |
| 650 | 4 | |a Safety | |
| 650 | 4 | |a Thrombolytic therapy | |
| 650 | 7 | |a Tissue Plasminogen Activator |2 NLM | |
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| 650 | 7 | |a Fibrinolytic Agents |2 NLM | |
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| 700 | 1 | |a Ma, Qingfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Huisheng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jianguo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Shigang |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Xiaoping |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yongqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yanyong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Runxiu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Liandong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Junyan |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Qilin |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Yongzhong |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Xiangyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Weidong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yongbo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yansong |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Wuwei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Xunming |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuping |e verfasserin |4 aut | |
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