This trial plans to compare prophylactic surfactant via MIST compared to rescue, to mirror the early surfactant trials . It is thought that prophylactic surfactant via an endotracheal tube resulted in ventilator associated lung injury as the explanation of why BPD was not decreased. Using MIST can avoid the positive pressure though an endotracheal tube and could decrease lung injury.

Multicenter, randomized, controlled trial.

Does prophylactic administration of exogenous surfactant in the delivery room, using a minimally-invasive technique, improve outcome in preterm infants 22-29 weeks gestation compared to rescue treatment?

Entry criteria: Inborn preterm infants 22 0/7-29 6/7 weeks gestation, will be randomized to prophylactic MIST surfactant in the delivery room compared to rescue surfactant when FiO2 is greater than or equal to 0.30 at less than 48 hours of age. Babies in both groups will be managed on CPAP pressures of 5-8 cm H2O.

Infants randomized to prophylactic surfactant treatment will receive a dose of poractant alfa (Curosurf) administered under direct laryngoscopy by a neonatologist, neonatal fellow, or neonatal nurse practitioner using a surfactant instillation catheter (MIST) 16G Angiocath (Becton Dickinson, Sandy, UT, USA), at a dosage of 200 mg/kg, which is the standard of care dosing for the first dose of surfactant, as soon as possible after delivery in the delivery room (within 15 minutes). Infants will be supported via CPAP in the delivery room and then transitioned to NCPAP in the NICU.

The control group will be given surfactant via MIST by a neonatologist, neonatal fellow, or neonatal nurse practitioner if their FiO2 reaches a threshold of 0.30 within the first 48 hours of life.

A second dose of poractant alfa (Curosurf), at a dosage of 100mg/kg, which is the standard of care dosing for all subsequent doses of surfactant after the first dose, will be administered via MIST to both groups if their FiO2 reaches the threshold of 0.30 between 6 and 48 hours after the first dose.

No further surfactant should be given in the first 7 days unless the infant reaches the intubation criteria.

POST-INTERVENTION MANAGEMENT

Other than the requirement to adhere to intubation criteria in the first week, and in some cases

perform a room air trial at 36 weeks corrected gestation, management will be at the discretion of the clinical team.

Titration of CPAP pressure is encouraged, with a permitted maximum of 8 cm H2O. Use of nasal intermittent positive pressure ventilation is allowable for apnea, but discouraged for RDS and should only be after at least one dose of surfactant has been given.

Early caffeine therapy is expected.

Criteria for intubation:

Enrolled infants on CPAP will be intubated if:

FiO2 0.45 for 15 minutes, or if there is unremitting apnea (> 6 episodes/hour requiring intervention or in the opinion of the treating physician) or persistent respiratory acidosis (pH<7.25 and pCO2 >60) on blood gasses at least 30 minutes apart or metabolic acidosis refractory to treatment.

Need for an anesthetic or an intervention requiring intubation.

OUTCOMES

Primary outcome: Intubation in the first 7 days of age.

Secondary outcomes:

Respiratory Incidence of composite outcome of death or physiological bronchopulmonary dysplasia (BPD). Durations of mechanical respiratory support, CPAP, high flow nasal cannula, (HFNC), oxygen therapy. Pneumothorax or pulmonary hemorrhage.

Non respiratory neonatal morbidities intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, and patent ductus arteriosus. Corrected age at discharge, length of hospital stay (a proxy for cost). Neonatal follow up data.

The above data will be collected until discharge. Babies born between 22 and 29 weeks are routinely followed by our developmental follow up clinic. The information from the 18 to 24 month developmental clinic visit will be recorded by the study.

RedCap, Epic