title: A pilot randomized, controlled trial of later treatment with a peptide-containing, synthetic surfactant for the prevention of bronchopulmonary dysplasia.
abstract: OBJECTIVE
  Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bronchopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia.
  
  
  METHODS
  Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of > or =0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation.
  
  
  RESULTS
  Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64%) compared with the placebo group (39%); no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both lucinactant groups (33%) compared with the placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was 66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality.
  
  
  CONCLUSIONS
  There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of lucinactant, and this warrants further investigation.
authors.affiliation: School of Medicine, University of North Carolina, Chapel Hill, NC, USA. matt_laughon@med.unc.edu
authors.forename: Matthew
authors.initials: M
authors.lastname: Laughon
authors.forename: Carl
authors.initials: C
authors.lastname: Bose
authors.forename: Fernando
authors.initials: F
authors.lastname: Moya
authors.forename: Judy
authors.initials: J
authors.lastname: Aschner
authors.forename: Steven Mark
authors.initials: SM
authors.lastname: Donn
authors.forename: Christopher
authors.initials: C
authors.lastname: Morabito
authors.forename: James John
authors.initials: JJ
authors.lastname: Cummings
authors.forename: Robert
authors.initials: R
authors.lastname: Segal
authors.forename: Carlos
authors.initials: C
authors.lastname: Guardia
authors.forename: Genzhou
authors.initials: G
authors.lastname: Liu
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D038622:Internationality; D008297:Male; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000627:therapeutic use; D010865:Pilot Projects; D011506:Proteins / Q000737:chemistry / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D005233:Fatty Alcohols; D010455:Peptides; D010715:Phosphatidylglycerols; D011506:Proteins; D011663:Pulmonary Surfactants; C502722:lucinactant