Non-invasive high frequency oscillation ventilation versus nasal CPAP as primary respiratory support in preterm neonates ≥ 30 weeks with RDS: A non-inferiority randomized controlled trial

Purpose To evaluate whether non-invasive high frequency oscillation ventilation (NHFOV) is non-inferior to nasal continuous positive airway pressure (CPAP) as primary non-invasive respiratory support (NRS) in preterm neonates of ≥ 30 weeks’ gestation with respiratory distress syndrome (RDS). Methods In this open-labelled randomized controlled trial (RCT) with a non-inferiority design conducted in a lower middle-income country, 142 preterm neonates were randomized to receive NHFOV (n = 71) or CPAP (n = 71) at equivalent pressures with nasal mask (NM) interface. A non-inferiority margin of 20% was pre-specified and a two-sided 90% confidence interval (CI) standardly used in non-inferiority trials was chosen. Results For the outcome treatment failure (requirement of an alternate NRS as rescue), the event rate was 4.2% in both groups, with a risk difference (RD) of 0.00 (90% CI, -0.06 to + 0.06). For IMV requirement, the RD was − 0.01 (90% CI, -0.04 to 0.01). Since upper limits of CIs for both primary outcomes were well below non-inferiority margin, NHFOV was proven to be non-inferior compared to CPAP. Duration of primary NRS was significantly lesser in NHFOV group, median difference (95% CI) being 7 hours lesser (-14 hours to 0 hours; p = 0.03). Conclusion In preterm neonates of ≥ 30 week’ gestation with RDS, NHFOV delivered through NM at equivalent pressures is non-inferior to CPAP when used as primary NRS. The finding of shorter NRS duration with NHFOV needs to be proven in adequately powered trials. Use of NM interface with equivalent pressures addresses the lacunae in the current literature on NHFOV, and provides a rigorous comparison between the two NRS modes.