POPART

Premature babies are at high-risk of respiratory failure due to respiratory distress syndrome (RDS). Surfactant given into the trachea is an effective treatment for infants who are intubated for RDS. Endotracheal intubation is difficult and is associated with adverse effects. A strategy of supporting premature newborns with continuous positive airway pressure (CPAP) and reserving intubation and surfactant for those who develop respiratory failure despite CPAP yields better results than intubating all infants for surfactant. However, nearly half of infants managed with CPAP are ultimately intubated for surfactant.
We will establish whether giving preterm infants surfactant into their oropharynx at birth, with the intention that they aspirate it, reduces the rate of intubation in the first 5 days of life.Infants born before 29 weeks gestation will be eligible for inclusion in this multi-centre randomised trial. Written informed consent will be obtained before delivery. Infants will be randomly assigned to receive oropharyngeal surfactant immediately at birth in addition to CPAP or standard care with CPAP alone. Caregivers will not be masked to group assignment.
Randomisation will be stratified by centre and gestation at birth (<26 weeks; 26-28 weeks). Primary outcome of the study is intubation for respiratory failure in the first 120 hours of life. Enrolled infants will be intubated for persistent apnoea and/or bradycardia in the delivery room (DR), or for respiratory failure in the neonatal intensive care unit (NICU) defined as ≥ 2 of worsening clinical signs; acidosis; oxygenation – FiO2 > 0.4; hypercarbia; or apnoea treated with mask ventilation. To demonstrate a reduction in the rate of the primary outcome from 48% in the control group to 26% with oropharyngeal surfactant with 80% power and a = 0.05, we need to recruit 250 infants. Adverse events will be recorded and measure secondary outcomes of clinical interest (rate of DR intubation; duration of ventilation and respiratory support; rate of bronchopulmonary dysplasia at day 28 and chronic lung disease at 36 weeks’ corrected age; mortality before hospital discharge). All outcomes will be determined at or before hospital discharge; this duration will vary according to clinical course [e.g. for 1 day (for participants who die shortly after enrolment) to several months]. Poractant alpha (Curosurf, Chiesi Farmeceutici, Parma, Italy) is a natural surfactant prepared from porcine lungs. It is approved for endotracheal use for prevention and/or treatment of RDS in premature infants. It is currently not licensed for oropharyngeal administration, therefore we will examine the off-label use of a licensed product. It is a randomised, parallel group, controlled Phase III trial.

Population: paediatric | Intervention type: therapeutic medicinal product