A multi-centre, double-blind, placebo-controlled study of liposomal prostaglandin E1 (TLC C-53) in patients with acute respiratory distress syndrome

Objective: To evaluate the safety of liposomal PGE I (TLC C-53) in patients with acute respiratory distress syndrome (ARDS), and determine its efficac y in improving oxygenation and reducing ventilator dependency. Design: A multi-centre, randomized, double-blind, placebo-controlled clinic al study. Setting: Thirty-one hospitals in six European countries. Patients: One hundred two patients with ARDS. Interventions: Patients were randomized in a 2:1 ratio to receive infusions of either the study drug TLC C-53 or placebo. Infusions were given over 60 min every 6 h for 7 days. The dose of study drug started at 0.6 mug/kg per h, rising over 24 h to a maximum dose of 1.8 mug/kg per h. Measurements and main results: Seventy patients received the study drug and 32 placebo. Sixty-nine patients (47 treatment, 22 placebo) completed the s tudy protocol. Patients were monitored for changes in the PaO2/FIO2 ratio, changes in lung compliance, time to off-ventilator and 28-day mortality, in addition to basic haematological and haemodynamic parameters. There were n o significant differences in demographics and baseline characteristics betw een the two groups. There were no differences in the time to off-ventilatio n (16 days with treatment, 16.6 days with placebo, p = 0.94) or in 28-day m ortality (30 % with treatment, 28 % with placebo, p = 0.78). There was a di fference in the time to achieve a PaO2/FIO2 ratio above 300 in favour of TL C C-53 (10.3 versus 26.5 days) but this was not statistically significant ( p = 0.23). Conclusions: TLC C-53 was generally well-tolerated but failed to reduce mor tality or duration of mechanical ventilation.