Effect of Neutrophil Elastase Inhibitor (Sivelestat Sodium) on Oxygenation in Patients with Sepsis-Induced Acute Respiratory Distress Syndrome.

Abstract

Objective: 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.

Methods: 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 PaO₂/FiO₂ ratio improvement on Day 5 after randomization, defined by a greater than 50% improvement in PaO₂/FiO₂ compared with that on ICU admission or PaO₂/FiO₂ reached over 300 mmHg on Day 5.

Results: 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 PaO₂/FiO₂ ratio improvement compared with 7/36 (19.4%) patients in the placebo group (risk difference, 0.36; 95% CI, 0.14 to 0.56, p<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; p=0.041).

Conclusion: 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.