Pilot study of the effects of ONO-5046 in patients with acute respiratory distress syndrome.

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.