title: A multicenter, randomized, masked, comparison trial of lucinactant, colfosceril palmitate, and beractant for the prevention of respiratory distress syndrome among very preterm infants.
abstract: OBJECTIVE
  Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved through the addition of peptides, such as sinapultide, that mimic the action of human surfactant protein-B (SP-B). A synthetic surfactant containing a mimic of SP-B may also reduce the potential risks associated with the use of animal-derived products. Our objective was to compare the efficacy and safety of a novel synthetic surfactant containing a functional SP-B mimic (lucinactant; Discovery Laboratories, Doylestown, PA) with those of a non-protein-containing synthetic surfactant (colfosceril palmitate; GlaxoSmithKline, Brentford, United Kingdom) and a bovine-derived surfactant (beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syndrome (RDS) and RDS-related death.
  
  
  METHODS
  We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of < or =32 weeks gestational age, to receive colfosceril palmitate (n = 509), lucinactant (n = 527), or beractant (n = 258) within 20 to 30 minutes after birth. Primary outcome measures were the rates of RDS at 24 hours and the rates of death related to RDS during the first 14 days after birth. All-cause mortality rates, bronchopulmonary dysplasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Primary outcomes, air leaks, and causes of death were assigned by an independent, masked, adjudication committee with prespecified definitions. The study was monitored by an independent data safety monitoring board.
  
  
  RESULTS
  Lucinactant reduced significantly the incidence of RDS at 24 hours, compared with colfosceril (39.1% vs 47.2%; odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.52-0.89). There was no significant difference in comparison with beractant (33.3%). However, lucinactant reduced significantly RDS-related mortality rates by 14 days of life, compared with both colfosceril (4.7% vs 9.4%; OR: 0.43; 95% CI: 0.25-0.73) and beractant (10.5%; OR: 0.35; 95% CI: 0.18-0.66). In addition, BPD at 36 weeks postmenstrual age was significantly less common with lucinactant than with colfosceril (40.2% vs 45.0%; OR: 0.75; 95% CI: 0.56-0.99), and the all-cause mortality rate at 36 weeks postmenstrual age was lower with lucinactant than with beractant (21% vs 26%; OR: 0.67; 95% CI: 0.45-1.00).
  
  
  CONCLUSIONS
  Lucinactant is a more effective surfactant preparation than colfosceril palmitate for the prevention of RDS. In addition, lucinactant reduces the incidence of BPD, compared with colfosceril palmitate, and decreases RDS-related mortality rates, compared with beractant. Therefore, we conclude that lucinactant, the first of a new class of surfactants containing a functional protein analog of SP-B, is an effective therapeutic option for preterm infants at risk for RDS.
authors.affiliation: Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. fernando.r.moya@uth.tmc.edu
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Moya
authors.forename: Janusz
authors.initials: J
authors.lastname: Gadzinowski
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bancalari
authors.forename: Vicente
authors.initials: V
authors.lastname: Salinas
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kopelman
authors.forename: Aldo
authors.initials: A
authors.lastname: Bancalari
authors.forename: Maria Katarzyna
authors.initials: MK
authors.lastname: Kornacka
authors.forename: T Allen
authors.initials: TA
authors.lastname: Merritt
authors.forename: Robert
authors.initials: R
authors.lastname: Segal
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schaber
authors.forename: Huei
authors.initials: H
authors.lastname: Tsai
authors.forename: Joseph
authors.initials: J
authors.lastname: Massaro
authors.forename: Ralph
authors.initials: R
authors.lastname: d'Agostino
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D001688:Biological Products / Q000627:therapeutic use*; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D007226:Infant Mortality; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology / Q000401:mortality; D019102:Infant, Very Low Birth Weight; D008297:Male; D010715:Phosphatidylglycerols / Q000627:therapeutic use*; D011506:Proteins / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000453:epidemiology / Q000517:prevention & control* / Q000628:therapy; D016019:Survival Analysis
chemical_list: D001688:Biological Products; D004338:Drug Combinations; D005233:Fatty Alcohols; D010715:Phosphatidylglycerols; D011506:Proteins; D011663:Pulmonary Surfactants; C502722:lucinactant; D015060:1,2-Dipalmitoylphosphatidylcholine; C081581:colfosceril palmitate; C072197:beractant