Journal Article

Randomized Clinical Trial of Activated Protein C for the Treatment of Acute Lung Injury

Siegel, Mark D, Peterson, Michael W, Matthay, Michael A, Eisner, Mark D, Kallet, Richard H, Phillips, Charles, Chesnutt, Mark S, Liu, Kathleen D, Brady, Sandra, Thompson, B. Taylor, Tidswell, Mark, Levitt, Joseph, Zhuo, Hanjing, Steingrub, Jay, Soto, Graciela, Weinacker, Ann

2008

Overview

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.

• Publisher: Am Thoracic Soc,American Lung Association,Oxford University Press,American Thoracic Society
• Subject: Adult / Aged / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Anticoagulants - therapeutic use / APACHE / Biological and medical sciences / Biomarkers / Blood. Blood coagulation. Reticuloendothelial system / C. Critical Care / Clinical trials / Double-Blind Method / FDA approval / Female / Humans / Intensive care medicine / Interleukin-6 - blood / Male / Mann-Whitney U test / Medical sciences / Middle Aged / Mortality / Pathogenesis / Pharmacology. Drug treatments / Plasma / Plasminogen Activator Inhibitor 1 - blood / Protein C - administration & dosage / Protein C - analysis / Protein C - therapeutic use / Proteins / Respiration, Artificial / Respiratory Dead Space / Respiratory distress syndrome / Respiratory Distress Syndrome - drug therapy / Respiratory Distress Syndrome - mortality / Respiratory Distress Syndrome - therapy / Sepsis / Treatment Failure / Ventilation / Ventilators