This open-label, non-inferiority randomized controlled trial conducted in a lower middle-income country compared non-invasive high-frequency oscillation ventilation (NHFOV) to nasal continuous positive airway pressure (CPAP) as primary non-invasive respiratory support (NRS) in preterm neonates ≥30 weeks' gestation with respiratory distress syndrome (RDS). The study enrolled 142 neonates, with 71 randomized to each group. Both interventions were delivered at equivalent pressures after lung recruitment using a nasal mask interface. A non-inferiority margin of 20% was pre-specified, with a two-sided 90% confidence interval used for analysis. For the primary outcome of treatment failure (requirement of an alternate NRS as rescue), the event rate was 4.2% in both groups, with a risk difference of 0.00 (90% CI -0.06 to +0.06). For the requirement of invasive mechanical ventilation (IMV), the risk difference was -0.01 (90% CI -0.04 to 0.01). Since the upper limits of the confidence intervals for both primary outcomes were below the non-inferiority margin, NHFOV was proven non-inferior to CPAP. Secondary outcomes showed the duration of primary NRS was significantly shorter in the NHFOV group, with a median difference of 7 hours less (95% CI -14 to 0; p=0.03). Ventilator-free days for primary NRS were also significantly higher in the NHFOV group, with a mean difference of 0.30 days (95% CI 0.00 to 0.60; p=0.02). The authors note that the finding of shorter NRS duration with NHFOV needs to be proven in adequately powered trials and that a superiority design RCT comparing these modalities may not be feasible due to the low baseline event rate of IMV, which would necessitate an impractically large sample size.
When a premature baby is born with respiratory distress syndrome (RDS), their lungs are stiff and need help to stay open so they can breathe. The standard first-line breathing support is called nasal CPAP, which delivers a steady stream of air. This study tested whether a newer method, called non-invasive high-frequency oscillation ventilation (NHFOV), is just as safe and effective when used as that first support.
The trial involved 142 premature babies, all at least 30 weeks along at birth, in a lower middle-income country. Half received the standard CPAP, and half received the newer NHFOV, both delivered through a nasal mask at the same pressure levels. The most important question was whether the newer method would fail, requiring a switch to a different support. The failure rate was identical for both groups: about 4 out of every 100 babies in each group needed to switch.
Crucially, the newer NHFOV method was proven to be just as safe as CPAP for preventing the need for a breathing tube and mechanical ventilation. Babies on the newer NHFOV also spent significantly less time on their primary breathing support—about 7 hours less on average—and had more days free from needing that support. The study concludes that NHFOV is a valid alternative to CPAP as the first breathing support for these babies, with the potential benefit of getting them off support sooner.
What this means for you: A newer breathing support method is just as safe as the standard one for premature babies with RDS and may get them off support faster.
View Original Abstract ↓
UNLABELLED: The purpose of this study is to evaluate if 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). In this open-label 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 after lung recruitment 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. For the outcome treatment failure (requirement of an alternate NRS as rescue), the event rate was 4.2% in both groups, risk difference (RD) with 90% CI being 0.00 (- 0.06 to + 0.06), and that for IMV requirement was - 0.01 (- 0.04 to 0.01). Since upper limits of CIs for both primary outcomes were well below the non-inferiority margin, NHFOV was proven to be non-inferior compared to CPAP. Duration of primary NRS was significantly lesser (median difference (MD) (95% CI), 7 h lesser (- 14 to 0); p = 0.03) and ventilator-free days for primary NRS were significantly higher (MD (95% CI), 0.30 days (0.00 to 0.60); p = 0.02) in the NHFOV group.
CONCLUSION: In preterm neonates of ≥ 30 weeks' 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.
TRIAL REGISTRATION: www.ctri.nic.in , id CTRI/2024/10/074939, registered on 8 October 2024.
WHAT IS KNOWN: • CPAP as initial respiratory support for preterm neonates with RDS is the standard of care in LMICs. • NHFOV is more efficacious than CPAP when used as a post-extubation respiratory support modality, evidence for the same being uncertain when used as primary support.
WHAT IS NEW: • NHFOV is non-inferior to CPAP as primary support in preterm neonates ≥ 30 weeks with RDS for the outcomes of treatment failure and IMV requirement with equivalent pressures after lung recruitment and nasal mask interface. • A superiority design RCT comparing these two non-invasive respiratory support modalities in this subgroup of preterm neonates may not be feasible. The low baseline event rate of IMV necessitates an impractically large sample size to achieve adequate power.