Aerosolized Surfactant in Mild Respiratory Distress Syndrome: Phase II Study

Background: Use of non-invasive ventilation (NIV) for initial respiratory support of preterm infants (PTI) with respiratory distress syndrome (RDS) not only averts the need for intubation but also delays surfactant instillation.

Objective: To evaluate the safety, feasibility and optimal dose of AS for treatment of RDS in PTI undergoing NIV in a Phase II RCT and to obtain pilot data on efficacy.

Design/Methods: PTI with a clinical diagnosis of RDS and receiving pre-defined NIV support for ≤8 hours were eligible after parental consent. A computer-generated randomization list was used to assign patients to 4 dosing schedules and 2 nebulizers within three GA strata (24-28, 29-32, 33-36 weeks).

All infants received a maximum of 2 doses of active medication. Clinical caregivers were blinded to the dose schedule.

Results: Of 149 subjects that received AS, 29 were in the lowest GA stratum and 60 each in the two higher GA strata. 94% of infants st dose of AS was 2.4 hours.

15 infants (10%) required intubation within 72 hours of AS. Comparison of primary outcome between GA strata, dosing schedules and nebulizers were not statistically significant.

AS was well tolerated by infants and clinical caregivers. Serious AEs included pneumothorax (n=2), surgical NEC (n=4); and one death after hospital discharge. Mild AEs included surfactant reflux from nose and mouth (18%), desaturations (11%), increased secretions (7%), dislodged prongs (4%), plugging of nasal prongs (3%), apnea (3%), and nebulizer malfunction (2%).

Conclusion(s): We have demonstrated the safety and feasibility of AS in PTI undergoing NIV. These results will inform the study design of a definitive Phase III trial.