中山大学第一附属医院关向东团队研究了胸腺肽α1治疗败血症（TESTS）的疗效和安全性。相关论文于2025年1月15日发表在《英国医学杂志》上。

为了评估免疫调节药物胸腺素α1是否能降低成人败血症的死亡率，2016年9月至2020年12月，研究组在中国的22个中心进行了一项多中心、双盲、安慰剂对照的3期临床试验。

研究组共招募了1106名年龄在18~85岁之间，根据sepsis-3标准诊断为败血症的成年人，以1:1的比例随机分配接受胸腺肽α1（n=552）或安慰剂（n=554）治疗。采用分层块法进行随机分组，参与者按年龄（<60岁和≥60岁）和中心分层。干预措施为每12小时皮下注射胸腺素α1或安慰剂，持续7天，除非因重症监护室出院、死亡或撤回同意书而停止。主要结局是随机分组后28天的全因死亡率。所有分析均基于改良意向治疗集，包括接受至少一剂研究药物的参与者。

在参与该研究的1106名败血症成年人中，1089人被纳入改良意向治疗分析（胸腺肽α1组n=542，安慰剂组n=547）。胸腺肽α1组127名参与者（23.4%）和安慰剂组132名参与者（24.1%）发生28天全因死亡（风险比0.99，95%置信区间0.77至1.27；对数秩检验P=0.93）。两组之间的次要或安全性结局没有统计学上的显著差异。预先指定的亚组分析显示，胸腺素α1对基于年龄（<60岁：风险比1.67，1.04至2.67；≥60岁：0.81，0.61至1.09；相互作用P=0.01）和糖尿病（糖尿病：0.58，0.35至0.99；无糖尿病：1.16，0.87至1.53；相互作用=0.04）的主要结局具有潜在差异作用。

综上，该试验未发现明确的证据表明，胸腺肽α1降低了脓毒症成人28天的全因死亡率。

附：英文原文

Title: The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial

Author: Jianfeng Wu, Fei Pei, Lixin Zhou, Weiqin Li, Renhua Sun, Yimin Li, Zheng Wang, Zhijie He, Xiaofei Zhang, Xiaodong Jin, Yun Long, Wei Cui, Chunting Wang, Erzhen Chen, Jun Zeng, Jing Yan, Qinhan Lin, Feihu Zhou, Lei Huang, You Shang, Meili Duan, Wei Zheng, Duming Zhu, Qiuye Kou, Shihong Zhang, Yin Liu, Chen Yao, Meixia Shang, Sui Peng, Qian Zhou, Kar Keung Cheng, Xiangdong Guan

Issue&Volume: 2025/01/15

Abstract:

Objective To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.

Design Multicentre, double blinded, placebo controlled phase 3 trial.

Setting 22 centres in China, September 2016 to December 2020.

Participants 1106 adults aged 18-85 years with a diagnosis of sepsis according to sepsis-3 criteria and randomly assigned in a 1:1 ratio to receive thymosin α1 (n=552) or placebo (n=554). A stratified block method was used for randomisation, and participants were stratified by age (<60 and ≥60 years) and centre.

Interventions Subcutaneous injection of thymosin α1 or placebo every 12 hours for seven days unless discontinued owing to discharge from the intensive care unit, death, or withdrawal of consent.

Main outcome measure The primary outcome was 28 day all cause mortality after randomisation. All analyses were based on a modified intention-to-treat set, including participants who received at least one dose of study drug.

Results Of 1106 adults with sepsis enrolled in the study, 1089 were included in the modified intention-to-treat analyses (thymosin α1 group n=542, placebo group n=547). 28 day all cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) in the placebo group (hazard ratio 0.99, 95% confidence interval 0.77 to 1.27; P=0.93 with log-rank test). No secondary or safety outcome differed statistically significantly between the two groups. The prespecified subgroup analysis showed a potential differential effect of thymosin α1 on the primary outcome based on age (<60 years: hazard ratio 1.67, 1.04 to 2.67; ≥60 years: 0.81, 0.61 to 1.09; P for interaction=0.01) and diabetes (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; P for interaction=0.04).

Conclusions This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis.

DOI: 10.1136/bmj-2024-082583

Source: https://www.bmj.com/content/388/bmj-2024-082583