Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter clinical trial.
OBJECTIVE
To evaluate the safety and efficacy of liposomal prostaglandin E1 (TLC C-53) in the treatment of patients with the acute respiratory distress syndrome (ARDS).


METHODS
Randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial.


METHODS
Eight community and university-affiliated hospitals in the United States.


METHODS
Twenty-five patients with ARDS.


METHODS
Patients were prospectively randomized in an unbalanced ratio within each site to receive either TLC C-53 (n = 17) or placebo (n = 8). Study drug was infused intravenously over 60 mins every 6 hrs for a 7-day period, starting at a dose of 0.15 micrograms/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 micrograms/kg/hr) was attained, intolerance to further increases developed, or invasive monitoring was discontinued. Patients received standard, aggressive, medical/surgical care throughout the trial.


RESULTS
Outcome measurements were Pao2/FI0(2), 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/FI0(2), 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 = .03). Improvement in PaO2/FIO2 during 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/FIO2 from baseline was 82.5 +/- 14.6 in the TLC C-53 group compared with 28.3 +/- 22.1 in the placebo group (p = .05). By day 8, lung compliance also increased from baseline significantly more in TLC C-53 patients than in placebo patients (5.7 +/- 1.7 vs -1.5 +/- 1.8 mL/cm H2O; p = .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 = .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.


CONCLUSIONS
In patients with ARDS, TLC C-53 was associated with improved oxygenation, increased lung compliance, and decreased ventilator dependency.
Abraham
E
E
University of Colorado, Department of Medicine, Denver, USA.
Park
Y C
YC
Covington
P
P
Conrad
S A
SA
Schwartz
M
M
D000328:Adult; D000527:Alprostadil / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy
D004337:Drug Carriers; D008081:Liposomes; D010975:Platelet Aggregation Inhibitors; D000527:Alprostadil