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

  1. Tiejun Wu
  2. Tao Wang
  3. Jinjiao Jiang
  4. Yue Tang
  5. Lina Zhang
  6. Zhiming Jiang
  7. Fen Liu
  8. Guiqing Kong
  9. Tingfa Zhou
  10. Ruijin Liu
  11. Haipeng Guo
  12. Jie Xiao
  13. Wenqing Sun
  14. Yuye Li
  15. Yingying Zhu
  16. Quan Liu
  17. Weifeng Xie
  18. Yan Qu
  19. Xiaozhi Wang
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Abstract

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 PaO2/FiO2ratio improvement on Day5 after randomization, defined by a greater than 50% improvement in PaO2/FiO2compared with that on ICU admission or PaO2/FiO2reached 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 PaO2/FiO2ratio 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.

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