Wu Tiejun, Wang Tao, Jiang Jinjiao, Tang Yue, Zhang Lina, Jiang Zhiming, Liu Fen, Kong Guiqing, Zhou Tingfa, Liu Ruijin, Guo Haipeng, Xiao Jie, Sun Wenqing, Li Yuye, Zhu Yingying, Liu Quan, Xie Weifeng, Qu Yan, Wang Xiaozhi
Department of Critical Care Medicine, Liaocheng People's Hospital, Liaocheng, 252004, People's Republic of China.
Department of Intensive Care unit, Binzhou Medical University Hospital, Binzhou, 256699, People's Republic of China.
J Inflamm Res. 2025 Mar 27;18:4449-4458. doi: 10.2147/JIR.S506549. eCollection 2025.
Neutrophil elastase (NE) plays an important role in the development of acute respiratory distress syndrome (ARDS). Sivelestat sodium, as a selective NE inhibitor, may improve the outcomes of patients with sepsis-induced ARDS in previous studies, but there is a lack of solid evidence. This trial aimed to evaluate the effect of sivelestat sodium on oxygenation in patients with sepsis-induced ARDS.
We conducted a multicenter, double-blind, randomized, placebo-controlled trial enrolling patients diagnosed with sepsis-induced ARDS admitted within 48 hours of the advent of symptoms. Patients were randomized in a 1:1 fashion to sivelestat or placebo. Trial drugs were administered as a 24-hour continuous intravenous infusion, for a minimum duration of 5 days and a maximum duration of 14 days. The primary outcome was the proportion of PaO/FiO ratio improvement on Day 5 after randomization, defined by a greater than 50% improvement in PaO/FiO compared with that on ICU admission or PaO/FiO reached over 300 mmHg on Day 5.
The study was stopped midway due to a potential between-group difference in mortality observed during the interim analysis. Overall, a total of 70 patients were randomized, of whom 34 were assigned to receive sivelestat sodium and 36 placebo. On day 5, 19/34 (55.9%) patients in the sivelestat group had PaO/FiO ratio improvement compared with 7/36 (19.4%) patients in the placebo group (risk difference, 0.36; 95% CI, 0.14 to 0.56, <0.001). The Kaplan-Meier curves showed a significantly improved 28-day survival rate in patients receiving sivelestat than those not (hazard ratio, 0.32; 95% CI, 0.11 to 0.95; =0.041).
In patients with sepsis-induced ARDS, sivelestat sodium could improve oxygenation within the first five days and may be associated with decreased 28-day mortality.
中性粒细胞弹性蛋白酶（NE）在急性呼吸窘迫综合征（ARDS）的发展过程中起重要作用。西维来司他钠作为一种选择性NE抑制剂，在既往研究中可能改善脓毒症诱导的ARDS患者的预后，但缺乏确凿证据。本试验旨在评估西维来司他钠对脓毒症诱导的ARDS患者氧合的影响。
我们进行了一项多中心、双盲、随机、安慰剂对照试验，纳入症状出现后48小时内入院的诊断为脓毒症诱导的ARDS的患者。患者以1:1的比例随机分为西维来司他组或安慰剂组。试验药物以24小时持续静脉输注的方式给药，最短持续5天，最长持续14天。主要结局是随机分组后第5天PaO₂/FiO₂比值改善的比例，定义为与入住重症监护病房（ICU）时相比PaO₂/FiO₂改善超过50%，或第5天时PaO₂/FiO₂达到300 mmHg以上。
由于中期分析时观察到组间死亡率存在潜在差异，该研究中途停止。总体而言，共有70例患者被随机分组，其中34例被分配接受西维来司他钠治疗，36例接受安慰剂治疗。在第5天，西维来司他组19/34（55.9%）的患者PaO₂/FiO₂比值有所改善，而安慰剂组为7/36（19.4%）（风险差异，0.36；95%置信区间，0.14至0.56，P<0.001）。Kaplan-Meier曲线显示，接受西维来司他治疗的患者28天生存率明显高于未接受治疗的患者（风险比，0.32；95%置信区间，0.11至0.95；P = 0.041）。
在脓毒症诱导的ARDS患者中，西维来司他钠可在头五天内改善氧合，且可能与28天死亡率降低有关。
