A MULTICENTER RANDOMIZED, MASKED COMPARISON TRIAL OF NATURAL VERSUS SYNTHETIC SURFACTANT FOR THE TREATMENT OF RESPIRATORY-DISTRESS SYNDROME

Objective: To compare the efficacy and safety of two surfactant prepar ations in the treatment of respiratory distress syndrome (RDS). Method s: We conducted a randomized, masked comparison trial at 21 centers. I nfants with RDS who were undergoing mechanical ventilation were eligib le for treatment with two doses of either a synthetic (Exosurf) or nat ural (Infasurf) surfactant if the ratio of arterial to alveolar partia l pressure of oxygen was less than or equal to 0.22. Crossover treatme nt was allowed within 96 hours of age if severe respiratory failure (d efined as two consecutive arterial/alveolar oxygen tension ratios less than or equal to 0.10) persisted after two doses of the randomly assi gned surfactant, Four primary outcome measures of efficacy (the incide nce of pulmonary air leak (less than or equal to 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of surviva l without bronchopulmonary dysplasia (BPD) at 28 days after birth) wer e compared by means of linear regression techniques. Results: The prim ary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study su rfactant, Preentry demographic characteristics and respiratory status were similar fdr the two treatment groups, except for a small but sign ificant difference in mean gestational age (0.5 week) that favored the Infasurf treatment group. Pulmonary air leak (less than or equal to 7 days) occurred in 21% of Exosurf- and 11% of Infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p less than or equal to 0.0001), During the 72 hours after the initia l surfactant treatment, the average fraction of inspired oxygen (+/- S EM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for Infasurf-trea ted infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/- SEM) was 8.6 +/- 0. 1 cm H2O for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infa nts (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H- 2o; p < 0.0001). The incidences of RDS-related death, total respirator y death, death to discharge, and survival without bronchopulmonary dys plasia at 28 days after birth did not differ. The number of days of mo re than 30% inspired oxygen and of assisted ventilation, but not the d uration of hospitalization, were significantly lower in Infasurf-treat ed infants. Conclusion: Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak comp lications.