title: Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial.
abstract: BACKGROUND
  Pulmonary coagulopathy may play a pathogenetic role in acute respiratory distress syndrome (ARDS), by contributing to alveolocapillary inflammation and increased permeability. Recombinant human activated protein C (rh-APC) may inhibit this process and thereby improve patient outcome.
  
  
  METHODS
  A prospective randomized, saline-controlled, single-blinded clinical trial was performed in the intensive care units of two university hospitals, and patients with ARDS were included within 24 h after meeting inclusion criteria.
  
  
  METHODS
  A 4-day course of intravenous rh-APC (24 mcg/kg/h) (n = 33) versus saline (n = 38).
  
  
  RESULTS
  The primary outcome parameter was the pulmonary leak index (PLI) of 67Gallium-transferrin as a measure of alveolocapillary permeability and secondary outcomes were disease severity scores and ventilator-free days, among others.
  
  
  RESULTS
  Baseline characteristics were similar; in 87% of patients the PLI was above normal and in 90% mechanical or non-invasive ventilation was instituted at a median lung injury score of 2.5. There was no evidence that Rh-APC treatment affected the PLI or attenuated lung injury and sequential organ failure assessment scores. Mean ventilator-free days amounted to 14 (rh-APC) and 12 days (saline, P = 0.35). 28-day mortality was 6% in rh-APC- and 18% in saline-treated patients (P = 0.12). There was no difference in bleeding events. The study was prematurely discontinued because rh-APC was withdrawn from the market.
  
  
  CONCLUSIONS
  There is no evidence that treatment with intravenous rh-APC during 4 days for infectious or inflammatory ARDS ameliorates increased alveolocapillary permeability or the clinical course of ARDS patients. We cannot exclude underpowering.
  
  
  BACKGROUND
  Nederlands Trial Register ISRCTN 52566874.
authors.affiliation: Department of Intensive Care, VU University Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cornet
authors.affiliation: Department of Intensive Care, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands; Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: A B Johan
authors.initials: AB
authors.lastname: Groeneveld
authors.affiliation: Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Jorrit J
authors.initials: JJ
authors.lastname: Hofstra
authors.affiliation: Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Vlaar
authors.affiliation: Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Pieter R
authors.initials: PR
authors.lastname: Tuinman
authors.affiliation: Department of Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Arthur
authors.initials: A
authors.lastname: van Lingen
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.affiliation: Department of Intensive Care, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Armand R J
authors.initials: AR
authors.lastname: Girbes
authors.affiliation: Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.affiliation: Department of Intensive Care, VU University Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands; Department of Intensive Care, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: Albertus
authors.initials: A
authors.lastname: Beishuizen
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*
chemical_list: D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated