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

Summary

In a multicenter, double-blind RCT (n=70) stopped early, sivelestat improved early oxygenation in sepsis-induced ARDS, with a signal toward lower 28-day mortality. Patients were randomized within 48 hours and received continuous infusion for 5–14 days.

Key Findings

• Multicenter, double-blind, randomized, placebo-controlled trial enrolled 70 patients within 48 hours of sepsis-induced ARDS onset.
• Sivelestat improved oxygenation within the first five days compared with placebo.
• Interim analysis suggested a between-group mortality difference; the trial was stopped early with a signal toward lower 28-day mortality in the sivelestat arm.

Clinical Implications

Sivelestat may be considered for study in larger confirmatory trials for sepsis-induced ARDS, and its early use could target neutrophil-driven lung injury. Current data are insufficient for routine adoption.

Limitations

• Stopped early with small sample size, underpowering definitive mortality conclusions.
• Abstract truncation limits detailed endpoint reporting; full data needed for appraisal.

Future Directions

Conduct adequately powered, CONSORT-compliant RCTs with mortality and ventilator-free days as primary endpoints, and biomarker-guided enrichment to identify responders.