Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter clinical trial
| Autor: | Paul Covington, Youn C. Park, Edward Abraham, Steven A. Conrad, Michael D. Schwartz |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
Male ARDS medicine.medical_treatment Pulmonary compliance Lung injury Critical Care and Intensive Care Medicine Placebo Double-Blind Method Intensive care Medicine Humans Prospective Studies Alprostadil Adverse effect Mechanical ventilation Drug Carriers Respiratory Distress Syndrome business.industry Respiratory disease respiratory system Middle Aged medicine.disease Respiration Artificial respiratory tract diseases Anesthesia Liposomes Female business Platelet Aggregation Inhibitors |
| Zdroj: | Critical care medicine. 24(1) |
| ISSN: | 0090-3493 |
| Popis: | 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). Design Randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial. Setting Eight community and university-affiliated hospitals in the United States. Patients Twenty-five patients with ARDS. Interventions Patients 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 Results Outcome 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/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 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 H2 O; 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. Conclusion In patients with ARDS, TLC C-53 was associated with improved oxygenation, increased lung compliance, and decreased ventilator dependency. |
| Databáze: | OpenAIRE |
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