title: A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury.
abstract: BACKGROUND
  Despite recent advances in critical care and ventilator management, acute lung injury and acute respiratory distress syndrome continue to cause significant morbidity and mortality. Granulocyte-macrophage colony stimulating factor may be beneficial for patients with acute respiratory distress syndrome.
  
  
  OBJECTIVE
  To determine whether intravenous infusion of granulocyte-macrophage colony stimulating factor would improve clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled clinical trial of human recombinant granulocyte-macrophage colony stimulating factor vs. placebo. The primary outcome was days alive and breathing without mechanical ventilatory support within the first 28 days after randomization. Secondary outcomes included mortality and organ failure-free days.
  
  
  METHODS
  Medical and surgical intensive care units at three academic medical centers.
  
  
  METHODS
  One hundred thirty individuals with acute lung injury of at least 3 days duration were enrolled, out of a planned cohort of 200 subjects.
  
  
  METHODS
  Patients were randomized to receive human recombinant granulocyte-macrophage colony stimulating factor (64 subjects, 250 μg/M) or placebo (66 subjects) by intravenous infusion daily for 14 days. Patients received mechanical ventilation using a lung-protective protocol.
  
  
  RESULTS
  There was no difference in ventilator-free days between groups (10.7 ± 10.3 days placebo vs. 10.8 ± 10.5 days granulocyte-macrophage colony stimulating factor, p = .82). Differences in 28-day mortality (23% in placebo vs. 17% in patients receiving granulocyte-macrophage colony stimulating factor (p = .31) and organ failure-free days (12.8 ± 11.3 days placebo vs. 15.7 ± 11.9 days granulocyte-macrophage colony stimulating factor, p = .16) were not statistically significant. There were similar numbers of serious adverse events in each group.
  
  
  CONCLUSIONS
  In a randomized phase II trial, granulocyte-macrophage colony stimulating factor treatment did not increase the number of ventilator-free days in patients with acute lung injury/acute respiratory distress syndrome. A larger trial would be required to determine whether treatment with granulocyte-macrophage colony stimulating factor might alter important clinical outcomes, such as mortality or multiorgan failure. (ClinicalTrials.gov number, NCT00201409 [ClinicalTrials.gov]).
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. Robert.paine@hsc.utah.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Paine
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Standiford
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Dechert
authors.forename: Marc
authors.initials: M
authors.lastname: Moss
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Martin
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Rosenberg
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Burnham
authors.forename: Morton B
authors.initials: MB
authors.lastname: Brown
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hyzy
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004311:Double-Blind Method; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012121:Respiration, Artificial; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor