We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Thrombolysis with Recombinant Human Prourokinase 4.5–6 h After Acute Ischemic Stroke: A Phase IIa, Randomized, and Open-Label Multicenter Clinical Trial.
- Authors
Song, Haiqing; Wang, Yuan; Ma, Qingfeng; Chen, Huisheng; Liu, Bo; Yang, Yi; Zhu, Jianguo; Zhao, Shigang; Jin, Xiaoping; Li, Yongqiu; Wang, Yanyong; Zhu, Runxiu; Zhao, Liandong; Liu, Junyan; Feng, Wuwei; Liu, Rui; Ji, Xunming; Wang, Yuping
- Abstract
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.
- Subjects
CHINA; NATIONAL Institutes of Health (U.S.); ISCHEMIC stroke; STROKE patients; CLINICAL trials; THROMBOLYTIC therapy; CEREBRAL hemorrhage
- Publication
CNS Drugs, 2024, Vol 38, Issue 1, p67
- ISSN
1172-7047
- Publication type
Article
- DOI
10.1007/s40263-023-01051-2