Background and purpose Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours. Methods and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III (TRACE III) is a multicentre, prospective, randomised, open-label, blind endpoint, controlled clinical trial. Patients who had an ischaemic stroke due to anterior circulation LVO (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5–24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume <70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) were included and randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or standard medical therapy. Specially, we will exclude patients who are intended for direct thrombectomy. All will be followed up for 90 days. Study outcomes Primary efficacy outcome is modified Rankin Scale (mRS) score ≤1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, major neurological improvement defined by a decrease ≥8 points compared with the initial deficit or a score ≤1 on the National Institutes of Health Stroke Scale (NIHSS) at 72 hours, mRS score ≤2 at 90 days, the rate of improvement on Tmax >6 s at 24 hours and NIHSS score change from baseline at 7 days. Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days. Discussion TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5 hours. Trial registration number [NCT05141305][1]. Data are available on reasonable request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05141305&atom=%2Fsvnbmj%2F9%2F1%2F82.atom

中文翻译：

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替奈普酶再灌注治疗急性缺血性脑血管事件 III (TRACE III) 的基本原理和设计：一项随机、III 期、开放标签对照试验

背景与目的重组人TNK组织型纤溶酶原激活剂(rhTNK-tPA)在4.5小时内治疗缺血性脑卒中的效果不逊色于阿替普酶。我们的研究旨在调查rhTNK-tPA对于因前循环大血管闭塞（LVO）超过4.5小时而发生缺血性卒中的患者的疗效和安全性。方法和设计 替奈普酶再灌注治疗急性缺血性脑血管事件 III (TRACE III) 是一项多中心、前瞻性、随机、开放标签、盲终点对照临床试验。自最后一次已知良好起 4.5-24 小时内因前循环 LVO（颈内动脉、大脑中动脉 M1 和 M2 段）而发生缺血性卒中（包括苏醒卒中和无目击卒中）且具有可挽救组织（缺血性卒中）的患者基于 CT 灌注或 MRI 灌注加权成像 (PWI) 的核心体积 <70 mL、错配率≥1.8 和错配体积≥15 mL）被纳入，并随机接受 rhTNK-tPA 0.25 mg/kg（单次推注），最多25 mg 或标准药物治疗。特别是，我们将排除打算进行直接血栓切除术的患者。所有这些都将被跟踪90天。研究结果 主要疗效结果是 90 天时改良 Rankin 量表 (mRS) 评分 ≤1。次要疗效结果包括 90 天时 mRS 的顺序分布、主要神经功能改善，定义为与初始缺陷相比减少 ≥8 分或 72 小时时美国国立卫生研究院卒中量表 (NIHSS) 评分 ≤ 1、mRS 评分 ≤ 2 在 90 天时，24 小时时 Tmax > 6 秒的改善率以及 7 天时 NIHSS 评分相对于基线的变化。安全性结果是 36 小时内出现症状性脑出血，90 天后死亡。讨论 TRACE III 将为 rhTNK-tPA 对于因前循环 LVO 超过 4.5 小时而发生缺血性卒中的患者的有效性和安全性提供证据。试用注册号[NCT05141305][1]。可根据合理要求提供数据。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05141305&atom=%2Fsvnbmj%2F9%2F1%2F82.atom