The Randomized, Controlled Trial of Late Surfactant: Effects on Respiratory Outcomes at 1-Year Corrected Age

Abstract

Objective To determine the effects of late surfactant on respiratory outcomes determined at one-year corrected age In the Trial of Late Surfactant (TOLSURF), which randomized extremely low gestational age newborns (ELGAN, ≤28 weeks’ gestational age) ventilated at 7–14 days to late surfactant and inhaled nitric oxide versus inhaled nitric oxide-alone (control). Study design Caregivers were surveyed in a double-blinded manner at 3, 6, 9 and 12 months corrected age to collect information on respiratory resource utilization (infant medication use, home support and hospitalization). Infants were classified for composite outcomes of Pulmonary Morbidity (No PM, determined in infants with no reported respiratory resource utilization) and Persistent PM (determined in infants with any resource utilization in ≥3 surveys). Results Infants (n=450, late surfactant n=217, control n=233) were 25.3±1.2 weeks’ gestation and 713±164g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group [35.8% versus 52.9%, Relative Benefit (RB) 1.28 (1.07, 1.55)]. There was no benefit of late surfactant for No PM versus PM (RB 1.27; 95% CI 0.89, 1.81) or No Persistent PM versus Persistent PM (RB 1.01; 95% CI 0.87, 1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89, 1.80) for No PM and RB 1.24 (95% CI 1.08, 1.42) for No Persistent PM. Conclusion Treatment of ELGAN with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity. Trial registration ClinicalTrials.gov: NCT01022580

A multidisciplinary quality improvement effort to reduce bronchopulmonary dysplasia incidence

“…Our "0.21 by 28" efforts demonstrate that a conscious effort to reduce FiO 2 while maintaining SpO 2 goals in the first 28 days-of-life resulted in improved pulmonary outcomes at 36-weeks PMA. Our results are consistent with a recent study by Wai et al [22], wherein a secondary analysis of the Trial of Late SURFactant to Prevent BPD data demonstrated that a lower cumulative supplemental oxygen exposure at DOL 14 correlated with a lower incidence of BPD or death [24,25]. Similarly, Stevens et al [26] reported that the area under the supplemental oxygen curve at DOL 72-h was a predictor of later respiratory symptoms and need for medications to treat them in very low birthweight infants.…”

Bronchopulmonary dysplasia

“…Based on evidence that extremely preterm infants exhibit persistent surfactant dysfunction, late or repeated surfactant administration has been explored. Although the TOLSURF trial showed no difference in survival at 36 weeks between infants without BPD receiving late surfactant administration versus no surfactant, there was a trend toward improvement at 40 weeks (with >20% decrease in the number infants requiring respiratory support at 40 weeks) and a substantial decrease in the number of infants who required home respiratory support during the first year 172,173 , an issue that is very important for parents because of the level of stress they experience.…”

Chronic Pulmonary Insufficiency of Prematurity: Developing Optimal Endpoints for Drug Development

“…Outcomes such as the need for re-hospitalization, home O2 therapy, and frequent visits to a health care provider or the emergency department in the first years of life have not been systematically reported in most studies, although this is beginning to change (24,25). The use of respiratory medications (e.g.…”