Abstract 1129 Poster Session IV, Tuesday, 5/4 (poster 331)

A multicenter, randomized, blinded, placebo-controlled trial was performed examining the safety and efficacy of rhSOD in premature infants receiving exogenous surfactant for the treatment of RDS, rhSOD (5 mg/kg suspended in 2 ml/kg saline) or placebo was instilled intratracheally to 301 infants with birthweight 600-1200g (stratified in 200g increments) within 4 hours of surfactant therapy. Infants were treated every 48 hours (as long as intubation was required) up to 28 days of life. Serial blood and urine studies, radiographs and ultrasounds were performed throughout the 28 day study period. Twenty-five infants died during the study period (survival 92%) and 23 (8%) dropped out of the study prematurely, but were still analyzed. rhSOD and placebo groups were comparable for birthweight (887 ± 166g), gestational age (26.6 ± 1.6 weeks), sex, ethnicity, use of antenatal steroids (78% received either a partial or complete course), maternal complications and delivery method, Apgar scores and growth parameters. Infants received an average of 1.6 (range 1-4) doses of exogenous surfactant for treatment of RDS and 7.1 (range 1-15) doses of the rhSOD study drug. The combined endpoint of death and/or the development of bronchopulmonary dysplasia (oxygen dependency at 28 days with Edwards radiographic scores ≥ 3; chest radiographs were interpreted in a "blinded" fashion by a single Pediatric Radiologist) was similar in both groups (rhSOD 38%, placebo 32%) as was oxygen requirement at 36 weeks post-conceptual age, days in oxygen, days of ventilation and total days in hospital. Neurosonograms were performed prior to drug administration, on day 7 (for intraventricular hemorrhage-IVH) and at day 28 (for periventricular leukomalacia-PVL). As reported by each center, the total number of infants with evidence of IVH at day 7 was comparable in both groups (32% placebo, 30% rhSOD). However, only 5 (3.6%) rhSOD treated infants developed a grade III or IV IVH compared to 13 (9.6%) infants receiving placebo, which represents a 62% decrease (p<0.05, Fisher's Exact Test). In addition, only 2 (1.5%) rhSOD treated infants developed PVL compare 3.9% infants receiving placebo. There were no other differences affecting outcome between groups. Data indicate that using this dosing and administration strategy, rhSOD does not appear to influence short-term pulmonary outcome, but may protect the brain from severe injury caused by oxygen free radicals. Long-term pulmonary and neurodevelopmental follow-up of these infants is currently being performed

Funded by Bio-Technology General Corporation, Iselin, NJ