DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED CANADIAN MULTICENTER TRIAL OF 2 DOSES OF SYNTHETIC SURFACTANT OR AIR PLACEBO IN 224 INFANTS WEIGHING 500 TO 749 GRAMS WITH RESPIRATORY-DISTRESS SYNDROME

In a multicenter, double-masked, placebo-controlled rescue trial condu cted at 12 Canadian hospitals, two 5 ml/kg doses of a synthetic surfac tant or air placebo were administered to 224 infants with birth weight s of 500 to 749 gm who had established respiratory distress syndrome a nd an arterial/alvealar oxygen tension ratio of less than 0.22. The fi rst dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to the infants continuing to receive mechanical v entilation. Infants were stratified at study entry by birth weight and gender. Infants receiving synthetic surfactant showed significant imp rovements in alveolar-arterial oxygen tension gradient, arterial/alveo lar oxygen tension ratio, and oxygen and ventilator requirements throu gh day 7. In the group randomized to synthetic surfactant, significant improvements were seen in oxygen requirements at the first time point measured (2 hours; p = 0.02), in the alveolar-arterial oxygen tension gradient by the second time point measured (6 hours; p = 0.03), and i n mean airway pressure after 6 hours. Overall mortality at 28 days was not significantly different in the two groups (50% vs 46%, air placeb o group vs synthetic surfactant group; p = 0.586). Similarly, neither the incidence of bronchopulmonary dysplasia (37% vs 30%, air placebo g roup vs synthetic surfactant group; p = 0.089) nor the incidence of su rvival without BPD through 28 days (17% vs 26%, respectively; p = 0.07 0) was significantly different in the two groups. No significant diffe rences in the incidence of safety-related outcomes or in adverse effec ts such as apnea or pulmonary hemorrhage were noted. These findings in dicate that rescue therapy with synthetic surfactant results in physio logic improvements in very tiny premature infants, but improvements in overall mortality or other complications of respiratory distress synd rome were not documented in the sample evaluated.