Evidence has linked
neutrophil elastase to
acute respiratory distress syndrome (ARDS), suggesting that inhibiting the activity of this
enzyme could prevent the development and progression of ARDS. However, few clinical trials have examined this notion. We therefore examined the effects of
ONO-5046 (
sivelestat, a specific inhibitor of
neutrophil elastase;
sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylaminobenzoyl]amino-
acetate tetrahydrate]) in a randomized, double-blinded trial in patients with ARDS. We randomly assigned 24 patients with ARDS to groups that received conventional
therapy without or with
sivelestat (0.2 mg. kg(-1). h(-1)) for 14 days. The variables of interest associated with clinical outcome were the duration of
mechanical ventilation; changes in oxygenation from baseline; changes in
cytokine levels from baseline; number of patients alive at 30 days who did not need
mechanical ventilation; and mortality rate. The length of intensive care unit stay, number of ventilation days, and mortality rates did not statistically differ between groups. ARDS was more persistent in the control than in the
sivelestat group (control, 19.5 +/- 7.4 days;
sivelestat, 13.5 +/- 5.9 days; P = 0.039).
Neutrophil elastase activity significantly differed between groups at 72 h
after treatment. Levels of
interleukin-6 were lower in the
sivelestat group than in the controls at 24, 48, and 72 h
after treatment.
ONO-5046 apparently did not affect survival or the duration of
mechanical ventilation.