Extreme preterm infant non-invasive surfactant trial (EPINIST)

Background: The majority of extremely premature infants receive mechanical ventilation despite current strategies for prevention. They remain at high risk of mortality, bronchopulmonary dysplasia (BPD) and other morbidities, and developmental disabilities. In an era of high use of antenatal corticosteroids for lung maturation and postnatal nCPAP, the optimal respiratory support strategy for extremely premature infants is currently unclear. Substantial practice variation exists including prophylactic intubation and surfactant either with immediate extubation or brief mechanical ventilation (goal <1 hour) and extubation to nCPAP, or nCPAP and rescue surfactant using various techniques. Primary clinical hypothesis: To determine if early surfactant administration via a thin catheter to spontaneously breathing preterm infants on nCPAP will reduce need for mechanical ventilation without an increase in neonatal morbidity or mortality compared to prophylactic surfactant with brief mechanical ventilation. Study objectives In extremely premature infants, the pilot study aims to determine the following to inform a larger definitive trial: 1. The feasibility and tolerance of delivery room thin catheter instillation of surfactant. 2. Effectiveness of prophylactic thin catheter surfactant in preventing intubation and mechanical ventilation. 3. Optimal enrolment and randomisation procedures. Study design This is a pilot parallel open label randomised controlled pilot study trial to one of 2 strategies of respiratory support and surfactant delivery. Study population All infants born at 24 weeks and 0 days to 27 weeks and 6 days completed gestation. Study interventions Infants born at <28 weeks: all infants with parental consent will be enrolled at birth and randomised to either: 1. Intubation, surfactant and brief mechanical ventilation 2. Nasal continuous positive airway pressure (nCPAP) with thin catheter surfactant Primary outcome [pilot study] 1. Intubation and mechanical ventilation 2. Incidence of events requiring resuscitation during surfactant administration (events requiring IPPV and/or intubation) Secondary outcomes Secondary outcomes include all major neonatal morbidities during hospital admission and neurodevelopmental outcomes at 3 years of age. Power and Sample Size 62 infants (31 each group) will be required to detect a 30% absolute reduction in the rate of intubation and ventilation in the first week after birth from 90% in the prophylactic / rescue surfactant group to 60% in the nCPAP with thin catheter surfactant group with a power of 80% at the p=0.05 level. For a 20% absolute risk reduction with 80% power at the p=0.05 level, 124 infants (62 each group) are required.