Intravenous Tenecteplase Prior to Endovascular Treatment for Ischemic Stroke at 4.5 to 24 Hours: The TNK-PLUS Randomized Clinical Trial.

Background

To investigate the adverse events and efficacy of tenecteplase prior to EVT in patients 4.5 to 24 hours after ischemic stroke onset due to proximal middle cerebral artery (MCA) occlusion.

研究旨在调查在近端大脑中动脉（MCA）闭塞导致的缺血性中风发作后4.5至24小时内，使用替奈普酶后再进行EVT的不良事件和疗效。

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, phase 3, randomized, open-label, blinded end point, superiority trial conducted at 40 centers in China.

设计、设置和参与者：在中国40个中心进行的多中心、第三阶段、随机、开放标签、盲终点、优效性试验。

Adult (≥18 years) patients with acute ischemic stroke 4.5 to 24 hours after last known to be well due to MCA-M1 or proximal M2 occlusion with salvageable brain tissue (ischemic core volume <70 mL, mismatch ratio ≥1.8, and mismatch volume ≥15 mL) identified on computed tomography-perfusion or magnetic resonance-perfusion-diffusion imaging were enrolled from January 25, 2024, through July 21, 2025, and followed up for 90 days.

招募了成年（≥18岁）急性缺血性中风患者，这些患者在最后一次被知晓状态良好后的4.5至24小时内，由于MCA-M1或近端M2闭塞，通过计算机断层扫描灌注或磁共振灌注扩散成像识别出可挽救的脑组织（缺血核心体积<70毫升，不匹配比率≥1.8，不匹配体积≥15毫升）。从2024年1月25日至2025年7月21日，患者被纳入研究，并进行了90天的随访。

Final follow-up occurred on October 14, 2025.

最终随访发生在2025年10月14日。

Methods

Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg) before EVT (n = 199) or EVT alone (n = 192).

符合条件的患者以1:1的比例随机分配接受静脉注射替奈普酶（0.25 mg/kg；最大剂量，25 mg）在EVT之前（n = 199）或仅接受EVT（n = 192）。

main_outcomes_and_measures

The primary outcome was functional independence, defined as a score of 0 to 2 on the modified Rankin Scale (range, 0-6, with higher scores indicating greater disability) at 90 days.

主要结果是功能独立性，定义为在90天时改良Rankin量表评分0至2分（范围0-6分，分数越高表示残疾程度越大）

Adverse events outcomes included symptomatic intracranial hemorrhage and death.

不良事件结果包括症状性颅内出血和死亡。

Results

All of the 391 patients enrolled (median age, 68 years [IQR, 59-75]; 155 [39.6%] females) completed the trial. Functional independence at 90 days occurred in 88 patients (44.2%) in the tenecteplase before EVT group and 83 patients (43.2%) in the EVT alone group (adjusted relative rate, 1.01 [95% CI, 0.83-1.24]; P = .89; risk difference, 0.99% [95% CI, -8.84% to 10.83%]).

所有纳入的391名患者（中位年龄68岁 [四分位数间距, 59-75]; 155名 [39.6%] 女性）完成了试验。在90天时，tenecteplase在EVT前组有88名患者（44.2%）和仅EVT组有83名患者（43.2%）实现了功能独立（调整后的相对率，1.01 [95% 置信区间, 0.83-1.24]; P = .89; 风险差异，0.99% [95% 置信区间, -8.84% 至 10.83%]）。

Mortality within 90 days was 12.7% (25/197) in the tenecteplase before EVT group and 14.2% (27/190) in the EVT alone group.

在90天内，tenecteplase在EVT前组的死亡率为12.7%（25/197），而仅EVT组的死亡率为14.2%（27/190）。

Symptomatic intracranial hemorrhage within 36 hours was 5.1% (10/197) and 2.6% (5/190), respectively.

在36小时内，分别有5.1%（10/197）和2.6%（5/190）的患者出现了症状性颅内出血。

conclusions_and_relevance

In patients presenting to EVT-capable centers 4.5 to 24 hours after stroke onset with proximal MCA occlusion, intravenous tenecteplase before EVT did not improve clinical outcomes vs EVT alone.

在中风发作后4.5至24小时到达有能力进行血管内治疗（EVT）的中心的患者中，与单独EVT相比，静脉注射替奈普酶并未改善临床结果。

trial_registration

ClinicalTrials.gov Identifier: NCT06221371.

临床试验注册号：NCT06221371。