SurfON trial: study protocol for a multicentre, open-label, randomised controlled trial of early surfactant therapy versus expectant management in late preterm and early term infants with respiratory distress

TL;DR

This study tests if early surfactant therapy improves outcomes for late preterm and early term infants with breathing difficulties.

Contribution

The trial introduces a large-scale randomized study to evaluate early surfactant therapy in late preterm and early term infants, a population with limited evidence-based guidelines.

Findings

The trial will assess if early surfactant therapy reduces neonatal hospital stays and severe respiratory failure.

It will also evaluate cost-effectiveness and other perinatal outcomes in this specific infant population.

The study addresses a gap in evidence-based care for late preterm and early term infants with respiratory distress.

Abstract

Late preterm and early term infants are a large proportion of all births. Historically, outcomes were thought to be similar to those of full term infants, but recent evidence demonstrates worse outcomes. Although serious morbidity is less common than in very preterm infants, the impact of modest illness in large numbers of more mature neonates is significant, with 30–40% requiring neonatal unit (NNU) admission, primarily for respiratory disease. The SurfON trial aims to evaluate whether early surfactant therapy improves outcomes compared with expectant management in late preterm and early term infants with respiratory distress. The primary objectives are to compare neonatal hospital stay and incidence of severe respiratory failure, with secondary objectives assessing other perinatal outcomes and cost-effectiveness.

The SurfON trial is a multicentre, open-label, randomised controlled trial involving 45 UK NNUs, aiming to recruit 1522 infants over 30 months. Eligible infants are those born at 34+0 to 38+6 weeks’ gestation who require noninvasive respiratory support for respiratory distress within 24 h of birth. Infants are randomised in a 1:1 allocation ratio to either early surfactant therapy or expectant management. Infants randomised to the early surfactant therapy group will receive a single dose of CUROSURF®, a natural animal-derived surfactant. IMP administration reflects local site policy and procedure and may be completed by any clinician for whom this falls within their usual scope of practice, following confirmation of eligibility. The IMP is a commonly used drug in neonates and is being used in line with standard care. Side effects are uncommon and usually transient. Timing and dosage of IMP administration will be collected. Surfactant is a stock drug for all NNUs and will be administered and accounted for as per local practice.

Evidence-based guidance for the management of late preterm and early term infants is sparse, and no previous large randomised controlled trials have focused on this population. Management of respiratory distress in late preterm and early term infants varies. Some clinicians prefer early surfactant administration to prevent deterioration—78others delay treatment to avoid mechanical ventilation. This inconsistency highlights the need for trials to establish an evidence base. Unexpected neonatal morbidity and prolonged hospitalisation cause significant psychological distress for families, impacting breastfeeding and maternal well-being. High intensive care workload and associated costs pose challenges for the NHS (National Health Service). Evidence-based management could improve outcomes and reduce healthcare burdens.

ISRCTN 15915394. Registered on 20th February 2020 https://www.isrctn.com/ISRCTN15915394.