Department of Neurology, Xuanwu Hospital, Capital Medicine University, Beijing, China.
Department of Neurology, Duke University School of Medicine, Durham, North Carolina.
JAMA Netw Open. 2023 Jul 3;6(7):e2325415. doi: 10.1001/jamanetworkopen.2023.25415.
Recombinant human prourokinase (rhPro-UK) is a thrombolytic agent that has shown promising findings in a phase 2 clinical trial in patients with acute ischemic stroke (AIS).
To evaluate the efficacy and safety of rhPro-UK thrombolysis within 4.5 hours of symptom onset in patients with AIS.
DESIGN, SETTING, AND PARTICIPANTS: This randomized, alteplase-controlled, open-label, phase 3 clinical trial was conducted from May 2018 to May 2020 at 35 medical centers in China. A total of 684 patients were screened and 674 patients were enrolled. Included patients were aged 18 to 80 years with a diagnosis of AIS and received treatment within 4.5 hours of stroke onset. Data were analyzed from June to October 2020.
Eligible patients were randomly assigned (1:1) to receive intravenous rhPro-UK or alteplase.
The primary objective was to assess whether rhPro-UK was noninferior to alteplase. The noninferiority margin was a between-group difference of less than 10%. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days.
Among 663 patients in the modified intention-to-treat population (mean [SD] age, 61.00 [10.20] years; 161 females [24.3%]), there were 330 patients in the rhPro-UK group and 333 patients in the alteplase group. The median (IQR) baseline National Institutes of Health Stroke Scale score was 6.00 (5.00-9.00). There were 23 deaths, and 619 patients (93.4%) completed the 3-month follow-up. The primary outcome occurred in 215 patients (65.2%) in the rhPro-UK group and 214 patients (64.3%) in the alteplase group (risk difference, 0.89; 95.4% CI, -6.52 to 8.29). Symptomatic intracerebral hemorrhage occurred in 5 patients (1.5%) in the rhPro-UK group and 6 patients (1.8%) in the alteplase group (P > .99). Systemic bleeding within 90 days occurred more frequently in the alteplase group (141 patients [42.2%]) than the rhPro-UK group (85 patients [25.8%]) (P < .001). By 90 days, 5 thrombolysis-related deaths each had occurred in the rhPro-UK group (1.5%) and alteplase group (1.5%) (P > .99).
This study found that intravenous rhPro-UK within 4.5 hours of AIS onset was noninferior to alteplase. The rhPro-UK group showed a similar rate of symptomatic ICH but fewer cases of systemic bleeding than the alteplase group.
ClinicalTrials.gov Identifier: NCT03541668.
重组人尿激酶原（rhPro-UK）是一种溶栓剂，在急性缺血性脑卒中（AIS）患者的 2 期临床试验中显示出良好的结果。
评估 rhPro-UK 在 AIS 发病后 4.5 小时内溶栓的疗效和安全性。
设计、地点和参与者：这是一项随机、阿替普酶对照、开放标签、3 期临床试验，于 2018 年 5 月至 2020 年 5 月在中国 35 个医疗中心进行。共筛选了 684 名患者，纳入了 674 名患者。纳入患者年龄为 18 至 80 岁，诊断为 AIS，并在发病后 4.5 小时内接受治疗。数据于 2020 年 6 月至 10 月进行分析。
符合条件的患者被随机分配（1:1）接受静脉注射 rhPro-UK 或阿替普酶。
主要目的是评估 rhPro-UK 是否不劣于阿替普酶。非劣效性边界为组间差异小于 10%。主要结局为 90 天时改良 Rankin 量表评分为 0 至 1。
在改良意向治疗人群（平均[标准差]年龄，61.00[10.20]岁；161 名女性[24.3%]）的 663 名患者中，rhPro-UK 组有 330 名患者，阿替普酶组有 333 名患者。基线国立卫生研究院卒中量表评分中位数（IQR）为 6.00（5.00-9.00）。有 23 例死亡，619 名患者（93.4%）完成了 3 个月的随访。rhPro-UK 组有 215 名患者（65.2%）和阿替普酶组有 214 名患者（64.3%）发生主要结局（风险差，0.89；95.4%CI，-6.52 至 8.29）。rhPro-UK 组有 5 名患者（1.5%）发生症状性颅内出血，阿替普酶组有 6 名患者（1.8%）发生症状性颅内出血（P>.99）。阿替普酶组（141 例[42.2%]）比 rhPro-UK 组（85 例[25.8%]）更频繁地发生 90 天内全身出血（P<.001）。到 90 天时，rhPro-UK 组（1.5%）和阿替普酶组（1.5%）各有 5 例溶栓相关死亡（P>.99）。
本研究发现，AIS 发病后 4.5 小时内静脉注射 rhPro-UK 不劣于阿替普酶。rhPro-UK 组症状性 ICH 发生率相似，但全身出血病例少于阿替普酶组。
ClinicalTrials.gov 标识符：NCT03541668。
