title: A clinical evaluation committee assessment of recombinant human tissue factor pathway inhibitor (tifacogin) in patients with severe community-acquired pneumonia.
abstract: BACKGROUND
  The purpose of this analysis was to determine the potential efficacy of recombinant human tissue factor pathway inhibitor (tifacogin) in a subpopulation of patients with community-acquired pneumonia (CAP) from a phase III study of severe sepsis.
  
  
  METHODS
  A retrospective review of patients with suspected pneumonia was conducted by an independent clinical evaluation committee (CEC) blinded to treatment assignment. The CEC reanalyzed data from patients enrolled in an international multicenter clinical trial of sepsis who had a diagnosis of pneumonia as the probable source of sepsis. The primary efficacy measure was all-cause 28-day mortality.
  
  
  RESULTS
  Of 847 patients identified on case report forms with a clinical diagnosis of pneumonia, 780 (92%) were confirmed by the CEC to have pneumonia. Of confirmed pneumonia cases, 496 (63.6%) met the definition for CAP. In the CEC CAP population, the mortality rates of the tifacogin and placebo groups were 70/251 (27.9%) and 80/245 (32.7%), respectively. The strongest signals were seen in patients with CAP not receiving concomitant heparin, having microbiologically confirmed infection, or having the combination of documented infection and no heparin. The reduction in mortality in this narrowly defined subgroup when treated with tifacogin compared with placebo was statistically significant (17/58 [29.3%] with tifacogin and 28/54 [51.9%] with placebo; unadjusted P value of less than 0.02).
  
  
  CONCLUSIONS
  Tifacogin administration did not significantly reduce mortality in any severe CAP patient. Exploratory analyses showed an improved survival in patients who did not receive concomitant heparin with microbiologically confirmed infections. These data support the rationale of an ongoing phase III study exploring the potential benefit of tifacogin in severe CAP.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00084071.
authors.affiliation: St Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate 10, 1200 Brussels, Belgium. laterre@rean.ucl.ac.be
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Steven P
authors.initials: SP
authors.lastname: LaRosa
authors.forename: Abla A
authors.initials: AA
authors.lastname: Creasey
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Lona
authors.initials: L
authors.lastname: Poole
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wunderink
mesh_terms: D018806:APACHE; D000368:Aged; D017326:Clinical Trials, Phase III as Topic; D017714:Community-Acquired Infections / Q000188:drug therapy; D005260:Female; D006088:Gram-Negative Aerobic Bacteria / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D011506:Proteins; C400709:Tifacogin