Safety and Efficacy of a Novel Aerosolized Surfactant (APC-0101) for the Treatment of Respiratory Distress Syndrome in Preterm Infants: A Randomized Phase 2b Study.

Abstract

To evaluate the efficacy of 2 different doses of aerosolized surfactant delivered by a drug/device combination system (APC-0101) in reducing the use of instilled liquid surfactant in preterm infants with respiratory distress syndrome (RDS). 261 preterm infants at 26-31 weeks' gestation with early RDS who were managed with nasal continuous positive airway pressure (NCPAP) or non-invasive ventilation (NIV) and had not received instilled liquid surfactant were randomized on the first day of life to 1 of 3 groups: control, low dose APC-0101, and high dose APC-0101. Infants in the two APC-0101 groups received up to 4 aerosolized surfactant treatments while on NCPAP/NIV. The primary outcome was the percentage of subjects who were treated with instilled liquid surfactant. Respiratory severity score (RSS) thresholds were pre-specified for subject selection and treatment algorithms. In the intent-to-treat (ITT) sample, the frequency of liquid surfactant instillation in the control group was 50.0% compared with 44.2% in the high dose APC-0101 group (P = 0.648). In exploratory analysis, the incidence of surfactant administration in the low dose APC-0101 group was 34.9% (P = 0.045 vs control). There were no differences between groups in other respiratory outcomes. The pre-specified high dose of aerosolized surfactant, delivered with the APC-0101 system, did not reduce the use of instilled liquid surfactant in infants with early RDS. An exploratory analysis of the low dose APC-0101 showed a reduction in instilled liquid surfactant, an observation that may merit evaluation in a subsequent study.