Nasal High Frequency Oscillatory Ventilation Versus Nasal Continuous Positive Airway Pressure in Preterm Infants Less than 34 Weeks Gestation: A Multicentre Randomized Clinical Trial

Background: Nasal high-frequency oscillatory ventilation (NHFOV) has been increasingly applied as a rescue respiratory support after failure of nasal continuous positive airway pressure (NCPAP) in preterm infants. However, the efficacy of NHFOV as the primary mode of respiratory support for preterm infants with respiratory distress syndrome (RDS) has not been proved. Methods: This multi-center randomized controlled trial was conducted in 18 tertiary neonatal intensive care units in China. A total of 302 preterm infants born at a gestational age of 260/7 to 336/7 weeks with a diagnosis of RDS was randomly assigned to either the NCPAP (n=150) or the NHFOV(n=152) group. The primary outcome was the need for invasive mechanical ventilation during the first 7 days after birth. Results: Treatment failure occurred in 15 of 152 infants (9.9%) in the NHFOV group and in 26 of 150 infants (17.3%) in the NCPAP group (P = 0.06). NHFOV resulted in a significantly lower rate of treatment failure than did NCPAP in the strata of 26+0/7 to 29+6 /7 weeks GA (11.9% vs 32.4%, P = 0.03) and BW<1500g (10.4% vs 29.6%, P = 0.01). Conclusions: NHFOV was not superior to NCPAP with regard to the primary outcome when applied as the primary respiratory support for RDS in infants between 26+0/7 and 33+6/7 weeks GA. In a secondary analysis, NHFOV seemed to improve effectiveness than NCPAP in preterm infants <30 weeks gestational age. Trial Registration: The trial was registered with ClinicalTrials.Gov(NCT03099694) Funding Statement: The trial was initiated and planned by the researchers and funded by Scientific Research Projects unit of Chongqing (Project- cstc2016shms-ztzx13001) Declaration of Interests: None of the authors have declared conflicts of interests to participate in this trial. Ethics Approval Statement: The trial was approved by the ethics committee of Daping Hospital and the Research Institute of Surgery of the Third Military Medical University and the institutional review boards of each of the participating centers.