MULTICENTER RANDOMIZED TRIAL COMPARING HIGH AND LOW-DOSE SURFACTANT REGIMENS FOR THE TREATMENT OF RESPIRATORY-DISTRESS SYNDROME (THE CUROSURF-4 TRIAL)

A randomised trial was conducted in 82 centres using the porcine surfa ctant extract, Curosurf, to compare two regimens of multiple doses to treat infants with respiratory distress syndrome and arterial to alveo lar oxygen tension ratio <0.22. Infants were randomly allocated to a l ow dosage group (100 mg/kg initially, with two further doses at 12 and 24 hours to a maximum cumulative total of 300 mg/kg; n 1069) or a hig h dosage group (200 mg/kg initially with up to four further doses of 1 00 mg/kg to a maximum cumulative total of 600 mg/kg; n = 1099). There was no difference between those allocated low and high dosage in the r ates of death or oxygen dependency at 28 days (51.1% v 50.8%; differen ce -0-3%, 95% confidence interval (CI) -4.6% to 3.9%), death before di scharge (25.0% v 23.5%; difference -1.5%, 95% CI -5.1% to 2.2%), and d eath or oxygen dependency at the expected date of delivery (32.2% v 31 .0%; difference -1.2%, 95% CI 5.2% to 2.7%). For 14 predefined seconda ry measures of clinical outcome there were no significant differences between the groups but the comparison of duration of supplemental oxyg en >40% did attain significance; 48.4% of babies in the low dose group needed >40% oxygen after three days compared with 42.6% of those in t he high dose group. The total amount of surfactant administered in the low dose regimen (mean 242 mg phospholipid/kg) was probably enough to replace the entire pulmonary surfactant pool. Adopting the low dose r egimen would lead to considerable cost savings, with no clinically sig nificant loss in efficacy.