Comparison of two fractions of inspired oxygen thresholds (0.25 vs 0.30) for surfactant administration in very preterm infants with respiratory distress syndrome under nasal intermittent positive pressure ventilation: study protocol for a multicentre randomised controlled, superiority trial.

INTRODUCTION

The combination of non-invasive ventilation, particularly nasal intermittent positive pressure ventilation (NIPPV), and exogenous surfactant therapy has been shown to significantly reduce mortality and morbidity in neonates with respiratory distress syndrome (RDS). The 2022 European Consensus Guidelines on RDS recommend a universal fraction of inspired oxygen (FiO₂) threshold of 0.30 for surfactant administration, irrespective of gestational age. However, this recommendation lacks validation through randomised controlled trials, and the optimal FiO₂ threshold remains uncertain. Therefore, this study aims to compare clinical outcomes associated with two different FiO₂ thresholds for surfactant administration (0.25 vs 0.30).

METHODS AND ANALYSIS: We designed a multicentre randomised, controlled, superiority trial investigating the effect of fraction of oxygen inspired (0.25 vs 0.30) in very preterm infants with RDS in 24 tertiary neonatal intensive care units in China. 394 preterm infants, born 26+⁰ to 31+6/7 weeks' gestation, will be randomised to the intervention (FiO₂ threshold: 0.25) or control (FiO₂ threshold: 0.30) group during initial NIPPV. The primary outcome will be NIPPV failure (the need for invasive mechanical ventilation (IMV) within 72 hours after birth).

ETHICS AND DISSEMINATION: Our protocol has been approved by the Ethics Committee of Jiangxi Maternal and Child Health Hospital. The study results will be disseminated to guardians and the public through public health education and neonatal academic conferences.

TRIAL REGISTRATION NUMBER: NCT07100652.