Randomized clinical trial of activated protein C for the treatment of acute lung injury AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Liu, K. D., Levitt, J., Zhuo, H., Kallet, R. H., Brady, S., Steingrub, J., Tidswell, M., Siegel, M. D., Soto, G., Peterson, M. W., Chesnutt, M. S., Phillips, C., Weinacker, A., Thompson, B. T., Eisner, M. D., Matthay, M. A. 2008; 178 (6): 618-623


Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days.To test the efficacy of activated protein C (APC) as a therapy for patients with ALI.Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 microg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days.APC increased plasma protein C levels (P = 0.002) and decreased pulmonary dead space fraction (P = 0.02). However, there was no statistically significant difference between patients receiving placebo (n = 38) or APC (n = 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P = 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P = 1.0). There were no differences in the number of bleeding events between the two groups.APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity.

View details for DOI 10.1164/rccm.200803-419OC

View details for Web of Science ID 000259158600011

View details for PubMedID 18565951

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