ObjectiveTo evaluate the safety and efficacy of an intravenous liposomal dispersion of prostaglandin E1as TLC C-53 in the treatment of patients with acute respiratory distress syndrome (ARDS).DesignRandomized, prospective, multicenter, double-blind, placebo-controlled, phase III clinical trial.SettingForty-seven community and university-affiliated hospitals in the United States.PatientsA total of 350 patients with ARDS were enrolled in this clinical trial.InterventionPatients were prospectively randomized in a 1:1 ratio to receive either liposomal prostaglandin E1or placebo. The study drug was infused intravenously for 60 mins every 6 hrs for 7 days starting with a dosage of 0.15 [micro sign]g/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 [micro sign]g/kg/hr) was attained or intolerance to further increases developed. Patients received standard aggressive medical/surgical care during the infusion period.Outcome MeasuresThe primary outcome measure was the time it took to wean the patient from the ventilator. Secondary end points included time to improvement of the PaO2/FIO2ratio (defined as first PaO2/FIO2300 mm Hg), day 28 mortality, ventilator dependence at day 8, changes in PaO2/FIO2, incidence of and time to development/resolution of organ failure other than ARDS.ResultsA total of 348 patients could be evaluated for efficacy. The distribution of variables at baseline describing gender, lung injury scores, Acute Physiology and Chronic Health Evaluation II scores, PaO2/FIO2, pulmonary compliance, and time from onset of ARDS or from institution of mechanical ventilation to the first dose of study drug was similar among patients in the liposomal prostaglandin E1(n = 177) and the placebo (n = 171) treatment arms. There was no significant difference in the number of days to the discontinuation of ventilation in the liposomal prostaglandin E1group compared with the placebo group (median number of days to off mechanical ventilation, 16.9 in patients receiving liposomal prostaglandin E1and 19.6 in those administered placebo; p = .94). Similarly, mortality at day 28 was not significantly different in the two groups (day 28 mortality, 57 of 176 (32%) in the liposomal prostaglandin E1group and 50 of 170 (29%) in patients receiving placebo; p = .55). In contrast, treatment with liposomal prostaglandin E1was associated with a significantly shorter time to reach a PaO2/FIO(2300 mm Hg (median number of days to reaching a PaO2/FIO2300 mm Hg: 9.8 days in the liposomal prostaglandin E145.9 [micro sign]g/kg) of liposomal prostaglandin E1(median number of days to discontinuation of ventilation, 10.3 in the liposomal prostaglandin E1group and 16.3 days in patients receiving placebo; p = .05). The overall incidence of serious adverse events was not significantly different in the liposomal prostaglandin E1(40%) or placebo-treated (37%) groups. Drug-related adverse events of all kinds were reported in 69% of the patients receiving liposomal prostaglandin E1compared with 33% of the placebo group, with hypotension and hypoxia (occurring in 52% and 24% of the liposomal prostaglandin E1-treatedpatients, respectively, and 17% and 5% of the placebo-treated patients, respectively) being noted most frequently.ConclusionsIn the intent-to-treat population of patients with ARDS, treatment with liposomal prostaglandin E1accelerated improvement in indexes of oxygenation but did not decrease the duration of mechanical ventilation and did not improve day 28 survival. (Crit Care Med 1999; 27:1478-1485)