Background and purpose Recombinant human prourokinase (rhPro-UK) is a new generation of specific plasminogen activator, that is non-inferior to alteplase in acute ischemic stroke. We aimed to investigate the efficacy and safety of rhPro-UK compared with standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset. Methods and design Prourokinase in mild ischemic stroke is a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Patients who had an acute ischemic stroke within 4.5 hours from symptom onset and with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 will be recruited. Patients will be randomly assigned (1:1) to receive intravenous rhPro-UK (35 mg) or standard medical treatment. The follow-up duration will be 90 days. The calculated sample size is 1446. Study outcomes Primary efficacy outcome is an excellent functional outcome, defined as a modified Rankin Scale (mRS) score ≤ 1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, mRS score ≤ 2 at 90 days, early neurological improvement at 24 hours (a decrease of NIHSS score ≥ 4 points compared with baseline or NIHSS score ≤ 1 point), Barthel index of 75–100 points at 90 days, quality of life at 90 days, and activities of daily living at 90 days. Safety outcomes are symptomatic intracranial haemorrhage within 36 hours, mortality at 90 days, moderate and severe systematic bleeding at 90 days, and adverse events/serious adverse events within 90 days. Discussion This large phase III randomised clinical trial will answer the question of whether thrombolysis is beneficial for acute mild ischemic stroke, and may provide evidence for rhPro-UK in patients had an acute mild ischemic stroke within 4.5 hours of symptom onset. Trial registration number [NCT05507645][1] Data are available upon reasonable request. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTNNCT05507645

中文翻译：

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尿激酶原治疗轻度缺血性中风 (PUMICE) 的基本原理和设计：一项多中心、前瞻性、随机、开放标签、盲态终点对照试验

背景与目的重组人尿激酶原(rhPro-UK)是新一代特异性纤溶酶原激活剂，在急性缺血性脑卒中的治疗效果不逊色于阿替普酶。我们的目的是研究 rhPro-UK 与标准药物治疗相比，对于症状出现 4.5 小时内的急性轻度缺血性中风的疗效和安全性。方法和设计 尿激酶原治疗轻度缺血性中风是一项多中心、前瞻性、随机、开放标签、盲终点对照试验。将招募症状出现后 4.5 小时内发生急性缺血性卒中且美国国立卫生研究院卒中量表 (NIHSS) 基线评分 ≤ 5 的患者。患者将被随机分配 (1:1) 接受静脉注射 rhPro-UK (35 mg) 或标准药物治疗。随访时间为90天。计算得出的样本量为 1446。 研究结果 主要疗效结果是优异的功能结果，定义为 90 天时改良 Rankin 量表 (mRS) 评分 ≤ 1。次要疗效结局包括 90 天时 mRS 的顺序分布、90 天时 mRS 评分 ≤ 2、24 小时时早期神经功能改善（与基线相比 NIHSS 评分降低 ≥ 4 分或 NIHSS 评分 ≤ 1 分）、Barthel 指数 75 – 90 天、90 天生活质量、90 天日常生活活动 100 分。安全性结局包括 36 小时内出现症状性颅内出血、90 天时死亡、90 天时中度和重度系统性出血以及 90 天内不良事件/严重不良事件。讨论 这项大型 III 期随机临床试验将回答溶栓治疗是否有益于急性轻度缺血性中风的问题，并可能为在症状出现 4.5 小时内发生急性轻度缺血性中风的患者提供 rhPro-UK 的证据。试验注册号 [NCT05507645][1] 可根据合理要求提供数据。[1]: /external-ref?link_type=ISRCTN&access_num=ISRCTNNCT05507645