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

© 2023. The Author(s)..

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 after the onset was 3.56 and 5.79 in the rhPro-UK 50 mg group and the rhPro-UK 35 mg group, respectively. The rates of functional independence at 90 days of rhPro-UK 50 mg and 35 mg were 61.54% and 69.23%, respectively (P = 0.475), and the proportion of patients with functional response to treatment at 24 h were 28.21% and 33.33% (P = 0.624). No sICH occurred in the two groups, and death occurred in only one patient in the rhPro-UK 50 mg group. There was no significant difference in mortality at 90 days and the rate of other serious adverse events between two groups.

CONCLUSION: In the 4.5-6 h time window, more than 60% of patients at either dose of rhPro-UK (50 mg or 35 mg) achieved functional independence at 90 days without increased mortality and sICH risk. Thus, intravenous rhPro-UK was effective and safe for patients with AIS within 4.5-6 h after stroke onset. While no significant differences were identified between different dosages of rhPro-UK regarding clinical outcomes, it is a logical step to further test the safety and efficacy of the low dose of rhPro-UK in a well-powered phase III study.

TRIAL REGISTRATION: http://www.chictr.org.cn . Identifier: ChiCTR1800016519. Date of registration: 6 June 2018.

Medienart:	E-Artikel

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	Zur Gesamtaufnahme - volume:38
Enthalten in:	CNS drugs - 38(2024), 1 vom: 27. Jan., Seite 67-75

Sprache:	Englisch

Beteiligte Personen:

Song, Haiqing [VerfasserIn] Wang, Yuan [VerfasserIn] Ma, Qingfeng [VerfasserIn] Chen, Huisheng [VerfasserIn] Liu, Bo [VerfasserIn] Yang, Yi [VerfasserIn] Zhu, Jianguo [VerfasserIn] Zhao, Shigang [VerfasserIn] Jin, Xiaoping [VerfasserIn] Li, Yongqiu [VerfasserIn] Wang, Yanyong [VerfasserIn] Zhu, Runxiu [VerfasserIn] Zhao, Liandong [VerfasserIn] Liu, Junyan [VerfasserIn] Feng, Wuwei [VerfasserIn] Liu, Rui [VerfasserIn] Ji, Xunming [VerfasserIn] Wang, Yuping [VerfasserIn]

Links:	Volltext

Themen:	Clinical Trial, Phase II EC 3.4.21.68 Fibrinolytic Agents Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Tissue Plasminogen Activator

Anmerkungen:	Date Completed 29.01.2024 Date Revised 19.04.2024 published: Print-Electronic Citation Status MEDLINE

doi:	10.1007/s40263-023-01051-2

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM365220078