title: Recombinant surfactant protein C-based surfactant for patients with severe direct lung injury.
abstract: BACKGROUND
  Patients with acute lung injury have impaired function of the lung surfactant system. Prior clinical trials have shown that treatment with exogenous recombinant surfactant protein C (rSP-C)-based surfactant results in improvement in blood oxygenation and have suggested that treatment of patients with severe direct lung injury may decrease mortality.
  
  
  OBJECTIVE
  Determine the clinical benefit of administering an rSP-C-based synthetic surfactant to patients with severe direct lung injury due to pneumonia or aspiration.
  
  
  METHODS
  A prospective randomized blinded study was performed at 161 centers in 22 countries. Patients were randomly allocated to receive usual care plus up to eight doses of rSP-C surfactant administered over 96 hours (n = 419) or only usual care (n = 424).
  
  
  RESULTS
  Mortality to 28 days after treatment, the requirement for mechanical ventilation, and the number of nonpulmonary organ failure-free days were not different between study groups. In contrast to prior studies, there was no improvement in oxygenation in patients receiving surfactant compared with the usual care group. Investigation of the possible reasons underlying the lack of efficacy suggested a partial inactivation of rSP-C surfactant caused by a step of the resuspension process that was introduced with this study.
  
  
  CONCLUSIONS
  In this study, rSP-C-based surfactant was of no clinical benefit to patients with severe direct lung injury. The unexpected lack of improvement in oxygenation, coupled with the results of in vitro tests, suggest that the administered suspension may have had insufficient surface activity to achieve clinical benefit.
authors.affiliation: Veterans Affairs Medical Center, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. rspragg@ucsd.edu
authors.forename: Roger G
authors.initials: RG
authors.lastname: Spragg
authors.forename: Friedemann J H
authors.initials: FJ
authors.lastname: Taut
authors.forename: James F
authors.initials: JF
authors.lastname: Lewis
authors.forename: Peter
authors.initials: P
authors.lastname: Schenk
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
authors.forename: Nathan
authors.initials: N
authors.lastname: Dean
authors.forename: Kenneth
authors.initials: K
authors.lastname: Krell
authors.forename: Andreas
authors.initials: A
authors.lastname: Karabinis
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D037721:Pulmonary Surfactant-Associated Protein C / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012121:Respiration, Artificial; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C; D011994:Recombinant Proteins