Multicentre open label, pragmatic randomised controlled trial of early surfactant therapy versus expectant management in late preterm and early term infants with respiratory distress

Research Question: In babies born at 34-38 weeks’ gestation with respiratory distress, where the clinical plan is to give non-invasive respiratory support(P), does early use of surfactant(I) compared with expectant management(C) result in shorter hospital stay and reduced failure to respond to treatment(O)? Background: Respiratory distress is common in late preterm (LP) and early term (ET) babies and their childhood respiratory outcomes are worse than those of full term babies. The commonest reason for neonatal unit (NNU) admission is respiratory distress syndrome due to surfactant deficiency. No evidence-based guidance exists for early respiratory management in this population and clinical practice varies widely. Many babies receive non-invasive respiratory support after birth. Some recover spontaneously but others go on to need mechanical ventilation and prolonged intensive care. It is difficult to predict which babies will deteriorate. Some clinicians use surfactant early to prevent respiratory deterioration; others choose to wait and give surfactant only if needed. The best strategy to prevent severe neonatal respiratory disease and reduce adverse long-term respiratory outcomes is not known. Aim: To investigate whether, in LP and ET infants with respiratory distress, early use of surfactant versus expectant management results in shorter duration of hospital stay and reduced disease severity. Objectives: A.To compare length of hospital stay and number of babies with failure to respond to treatment in LP and ET babies receiving early surfactant, versus those receiving expectant management. B.To investigate the effectiveness and cost-effectiveness of early surfactant therapy on important secondary outcomes C.To examine the impact of early surfactant therapy on parent/carer health-related quality of life D.To examine, using economic evaluation, whether any benefits associated with early surfactant therapy are justified by resource implications needed to deliver the treatment. E.To undertake an internal pilot study to assess recruitment and retention of participants, delivery of interventions, assess protocol adherence, monitor safety and evaluate completeness of data collection. Methods: We will conduct a multicentre, randomised controlled trial of early surfactant versus expectant management in LP and ET babies admitted to a NNU with respiratory distress, where a clinical decision has been taken to provide non-invasive respiratory support. Eligible babies whose mothers give consent and who have been allocated to the treatment arm at randomisation will receive 100-200mg/kg surfactant, in line with usual clinical practice, and non-invasive respiratory support according to local practice. Babies allocated to the control arm will receive non-invasive respiratory support alone. Babies in either trial arm may receive 'rescue' surfactant at the attending clinician's discretion if they meet pre-defined criteria for severe respiratory disease. Following the trial, we will study hospital admissions to one year using data linkage. Timeline: 6 months set up, 63 months accrual(with internal pilot) 6 months analysis and dissemination; duration 75 months. Health economic analysis at 1 year corrected age. Impact and dissemination: Results will be disseminated via Bliss and other parent organisations. Dissemination to professionals will be via professional bodies, conferences and peer-reviewed publications. Results will inform national guidance to ensure cost-effective, evidence-based care for LP and ET babies.