title: A Search for subgroups of patients with ARDS who may benefit from surfactant replacement therapy: a pooled analysis of five studies with recombinant surfactant protein-C surfactant (Venticute).
abstract: BACKGROUND
  Studies to date have shown no survival benefit for the use of exogenous surfactant to treat patients with the ARDS. To identify specific patient subgroups for future study, we performed an exploratory post hoc analysis of clinical trials of recombinant surfactant protein-C (rSP-C) surfactant (Venticute; Nycomed GmbH; Konstanz, Germany).
  
  
  METHODS
  We performed a pooled analysis of all five multicenter studies in which patients with ARDS due to various predisposing events were treated with rSP-C surfactant. Patients received either usual care (n = 266) or usual care plus up to four intratracheal doses (50 mg/kg) of rSP-C surfactant (n = 266). Factors influencing the study end points were analyzed using descriptive statistics, analysis of covariance, and logistic regression models.
  
  
  RESULTS
  ARDS was most often associated with pneumonia or aspiration, sepsis, and trauma or surgery. For the overall patient population, treatment with rSP-C surfactant significantly improved oxygenation (p = 0.002) but had no effect on mortality (32.6%). Multivariate analysis showed age and acute physiology and chronic health evaluation (APACHE) II score to be the strongest predictors of mortality. In the subgroup of patients with severe ARDS due to pneumonia or aspiration, surfactant treatment was associated with markedly improved oxygenation (p = 0.0008) and improved survival (p = 0.018).
  
  
  CONCLUSIONS
  rSP-C surfactant improved oxygenation in patients with ARDS irrespective of the predisposition. Post hoc evidence of reduced mortality associated with surfactant treatment was obtained in patients with severe respiratory insufficiency due to pneumonia or aspiration. Those patients are the focus of a current randomized, blinded, clinical trial with rSP-C surfactant.
authors.affiliation: Department of Clinical Research, Nycomed, Konstanz, Germany.
authors.forename: Friedemann J H
authors.initials: FJH
authors.lastname: Taut
authors.affiliation: Department of Biometrics, Omnicare Clinical Research, Cologne, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Rippin
authors.affiliation: Department of Internal Medicine IV, General Hospital Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Schenk
authors.affiliation: Department of Intensive Care, University Hospital of Wales, Cardiff, UK.
authors.forename: George
authors.initials: G
authors.lastname: Findlay
authors.affiliation: Department of Clinical Research, Nycomed, Konstanz, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Wurst
authors.affiliation: Department of Clinical Research, Nycomed, Konstanz, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Häfner
authors.affiliation: St. Joseph's Health Center, University of Western Ontario, London, ON, Canada.
authors.forename: James F
authors.initials: JF
authors.lastname: Lewis
authors.affiliation: Department of Pulmonology, Justus-Liebig University, Giessen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Department of Pulmonology, Justus-Liebig University, Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Diego and the San Diego VA Healthcare System, La Jolla, CA. Electronic address: rspragg@ucsd.edu.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Spragg
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007322:Instillation, Drug; D008297:Male; D008875:Middle Aged; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D014132:Trachea; D016896:Treatment Outcome
chemical_list: D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; C521929:Venticute