ObjectiveTo evaluate the safety and efficacy of liposomal prostaglandin E1(TLC C-53) in the treatment of patients with the acute respiratory distress syndrome (ARDS).DesignRandomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial.SettingEight community and university-affiliated hospitals in the United States.PatientsTwenty-five patients with ARDS.InterventionsPatients were prospectively randomized in an unbalanced ratio within each site to receive either TLC C-53 (n equals 17) or placebo (n equals 8). Study drug was infused intravenously over 60 mins every 6 hrs for a 7-day period, starting at a dose of 0.15 micro gram/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 micro gram/kg/hr) was attained, intolerance to further increases developed, or invasive monitoring was discontinued. Patients received standard, aggressive, medical/surgical care throughout the trial.Measurements and Main ResultsOutcome measurements were PaO2/FIO2, dynamic pulmonary compliance, ventilator dependence on day 8, and 28-day all-cause mortality rate. At baseline, the distribution of variables describing Lung Injury Scores, Acute Physiology and Chronic Health Evaluation II scores, PaO2/FIO2, pulmonary compliance, and time from onset of ARDS to first dose of study drug was similar between patients in the TLC C-53 and placebo treatment groups. On day 8, all eight patients given placebo required mechanical ventilation, while eight of 17 patients given TLC C-53 were healthy enough to be removed from the ventilator (p equals .03). Improvement in PaO2/FIO2during the initial 8-day study period was greater in patients receiving TLC C-53. This trend achieved statistical significance on day 3, when the increase in PaO2/FIO2from baseline was 82.5 plus minus 14.6 in the TLC C-53 group compared with 28.3 plus minus 22.1 in the placebo group (p equals .05). By day 8, lung compliance also increased from baseline significantly more in TLC C-53 patients than in placebo patients (5.7 plus minus 1.7 vs. minus 1.5 plus minus 1.8 mL/cm H2O; p equals .01). The 28-day mortality rate was 6% (1/17 patients) in the TLC C-53 group and 25% (2/8 patients) in the placebo group (p equals .23). Drug-related adverse events were reported in 82% of the patients receiving TLC C-53 compared with 38% of the placebo group, with half of the adverse events in the TLC C-53 group being localized infusion site irritation. TLC C-53 was hemodynamically well tolerated, with transient hypotension occurring in three patients.ConclusionIn patients with ARDS, TLC C-53 was associated with improved oxygenation, increased lung compliance, and decreased ventilator dependency.(Crit Care Med 1996; 24:10-15)