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

Objectives 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 administrated 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 PaO 2 /FiO 2 ratio improvement on Day5 after randomization, defined by a greater than 50% improvement in PaO 2 /FiO 2 compared with that on ICU admission or PaO 2 /FiO 2 reached over 300 mmHg on Day5. 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 sivelastat sodium and 36 placebo. On day5, 19/34 (55.9%) patients in the sivelastat group had PaO 2 /FiO 2 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.