Randomized clinical trial of activated protein C for the treatment of acute lung injury

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

Research output: Contribution to journalArticlepeer-review

183 Scopus citations


Rationale: 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. Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI. Methods: 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 μg/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. Measurements and Main Results: 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. Conclusions: 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. Clinical trial registered with www.clinicaltrials.gov (NCT 00112164).

Original languageEnglish (US)
Pages (from-to)618-623
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Issue number6
StatePublished - Sep 15 2008
Externally publishedYes


  • Activated protein C
  • Acute lung injury
  • Acute respiratory distress syndrome
  • Mortality
  • Ventilator-free days

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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