title: Pediatric calfactant in acute respiratory distress syndrome trial.
abstract: BACKGROUND
  Our previous studies in children with acute lung injury/acute respiratory distress syndrome demonstrated improved outcomes with exogenous surfactant (calfactant) administration. Sample sizes in those studies were small, however, and the subject populations heterogeneous, thus making recommendations tenuous.
  
  
  OBJECTIVE
  To investigate the efficacy of surfactant administration in a larger, more homogenous population of children with lung injury/acute respiratory distress syndrome due to direct lung injury.
  
  
  METHODS
  Masked, randomized, placebo-controlled trial in 24 children's hospitals in six different countries.
  
  
  METHODS
  Children 37 weeks postconception to 18 years old with lung injury/acute respiratory distress syndrome due to direct lung injury were randomized to receive up to three doses of 30 mg/cm height of surfactant (calfactant) versus placebo (air) within 48 hours of intubation and initiation of mechanical ventilation. The primary outcome was mortality at 90 days. Ventilator-free days, changes in oxygenation, and adverse events were also assessed.
  
  
  RESULTS
  The study was stopped at the sponsor's request after the second interim analysis for presumed futility. A total of 110 subjects were enrolled, with consent withdrawn from one whose data are unavailable. There were no significant differences between groups except in hospital-free days (10.4 ± 7.8 placebo vs 6.4 ± 7.8 surfactant; p = 0.01). Overall 90-day mortality was 11% (seven surfactant, five placebo). No immediate improvement in oxygenation was associated with surfactant administration.
  
  
  CONCLUSIONS
  Surfactant did not improve outcomes relative to placebo in this trial of children with direct lung injury/acute respiratory distress syndrome. Differences in concentration of the surfactant, failure to recruit the lung during surfactant administration, or using two rather than four position changes during administration are possible explanations for the difference from previous studies. Exogenous surfactant cannot be recommended at this time for children with direct lung injury/acute respiratory distress syndrome.
authors.affiliation: 1Department of Pediatrics, University of Virginia Health Sciences System, Charlottesville, VA. 2Department of Pediatrics, Penn State Hershey M.S. Hershey Medical Center, Hershey, PA. 3Department of Pediatrics, Children's Hospital & Medical Center, University of Nebraska, Omaha, NE. 4Department of Internal Medicine, University of Virginia Health Sciences System, Charlottesville, VA. 5Public Health Sciences, University of Virginia Health Sciences System, Charlottesville, VA. 6Department of Pediatrics, Children's Hospital Cleveland Clinic, Cleveland, OH. 7Pneuma Pharmaceuticals, Amherst, NY. 8Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Willson
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
authors.forename: Robert
authors.initials: R
authors.lastname: Tamburro
authors.forename: Edward
authors.initials: E
authors.lastname: Truemper
authors.forename: Jonathon
authors.initials: J
authors.lastname: Truwit
authors.forename: Mark
authors.initials: M
authors.lastname: Conaway
authors.forename: Christine
authors.initials: C
authors.lastname: Traul
authors.forename: Edmund E
authors.initials: EE
authors.lastname: Egan
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000401:mortality; D001688:Biological Products / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000401:mortality
chemical_list: D001688:Biological Products; D011663:Pulmonary Surfactants; C117342:calfactant