A double-blind placebo-controlled study to evaluate the safety and efficacy of L-2-oxothiazolidine-4-carboxylic acid in the treatment of patients with acute respiratory distress syndrome

Objective: Acute respiratory distress syndrome is an abrupt inflammatory illness that involves damage from reactive oxygen species. We examined the efficacy and safety of oxothiazolidine-4-carboxylic acid (OTZ), a free radical scavenger, in treating acute respiratory distress syndrome. Design. Double-blind, placebo-controlled trial. Setting: Multicentered study. Patients. Patients with a Pao(2)/Fio(2) <= 200 and bilateral infiltrates on chest radiograph, and requiring mechanical ventilation. Interventions. We randomized 215 patients to receive OTZ, 210 mg/kg per day every 8 hrs for 14 days or placebo. Measurements and Main Results. Ventilator-free days (the number of days alive and free from ventilator requirement) during the first 30 days of study were 8.3 vs. 13.5 days for the OTZ and placebo groups, respectively (p <.001). Mortality was 30/101 (29.7%) in the OTZ group and 18/114 (15.8%) in the placebo group during the 30-day study period (p =.014). This study was terminated prematurely for safety reasons after 215 of the planned 352 patients were enrolled. Conclusions. OTZ does not improve survival or reduce ventilator time in patients with acute respiratory distress syndrome and may worsen outcome, although mortality in the OTZ group was similar or lower than most similar trials. Alternatively, our results may be best explained by the unusually excellent outcome in the placebo group.