A Multicenter, Randomized, Masked, Comparison Trial of Lucinactant, Colfosceril Palmitate, and Beractant for the Prevention of Respiratory Distress Syndrome Among Very Preterm Infants

Background and Objective. Evidence sug- gests that synthetic surfactants consisting solely of phos- pholipids can be improved through the addition of pep- tides, such as sinapultide, that mimic the action of hu- man 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 sur- factant (beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syn- drome (RDS) and RDS-related death. Methods. We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of <32 weeks gestational age, to receive colfosceril palmi- tate (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 dys- plasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Pri- mary outcomes, air leaks, and causes of death were as- signed by an independent, masked, adjudication com- mittee with prespecified definitions. The study was monitored by an independent data safety monitoring board. Results. Lucinactant reduced significantly the inci- dence 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 differ- ence 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 com- mon 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 surfac- tant preparation than colfosceril palmitate for the pre- vention of RDS. In addition, lucinactant reduces the in- cidence 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. Pediatrics 2005;115: 1018-1029; lucinactant, colfosceril palmitate, beractant, surfactant, respiratory distress syndrome.