NIV-MISA-NRDS Trial: a Multicenter Study in China

BACKGROUND Non-invasive ventilation (NIV) treatment have been developed to minimize lung damage and to avoid invasive mechanical ventilation (IMV) in preterm infants, especially in those with gestational age less than 30 weeks. Our hypothesis is that for preterm infants less than 30 weeks with potential to develop neonatal respiratory distress syndrome (NRDS), nasal continuous positive airway pressure (NCPAP) is non-inferior to the nasal intermittent positive pressure ventilation (NIPPV) as primary respiratory support before minimal invasive surfactant administration (MISA). DESIGN, SETTING, AND PARTICIPANTS The NIV-MISA-NRDS trial is planned as an unblinded, multicenter, randomized, non-inferiority trial at 11 tertiary care neonatal intensive care units in China. Eligible infants are preterm infants of 24 to 29+6 weeks' gestational age who have spontaneous breaths at birth and require primary NIV support for NRDS in the first 2 h of life. Infants are randomized 1:1 to treatment with either NCPAP or NIPPV once admitted into neonatal intensive care unit (NICU). If the patient with progressively aggravates respiratory distress and clinically diagnose as NRDS, pulmonary surfactant will be supplemented by minimal invasive surfactant administration (MISA) in the first 2 hours . MAIN OUTCOMES AND MEASURES The primary outcome is NIV treatment failure within 72 hours after birth, as determined by objective oxygenation, blood gas, and apnea criteria, or the need for intubation and mechanical ventilation. Secondary outcomes mainly include the incidence of complications during hospitalization . With a specified noninferiority margin of 10%, using a two-sided 95% CI and 80% power, the study requires 480 infants per group (total 960 infants in the study).