Initial supplementary oxygen concentration for moderate-late preterm infants receiving respiratory support in the delivery room: statistical analysis plan for the multicenter, cluster-randomized crossover AIROPLANE Trial.

backgroundModerate-late preterm infants born at 32-35 completed weeks' gestation constitute a large proportion of all preterm births (< 37 weeks' gestation), yet they are not well represented in the newborn resuscitation literature. Preterm infants often receive respiratory support in the delivery room, and recommendations exist to guide the use of supplemental oxygen when providing this support. However, there are minimal data regarding the best initial supplementary oxygen concentration for moderate-late preterm infants requiring respiratory support at birth, resulting in practice variation. The aim of the AIROPLANE trial is to compare initial supplementary oxygen concentrations of 30% and 21% (air) in preterm infants of 32-35 weeks' gestation who require respiratory support in the delivery room, with a primary outcome of the need for ongoing respiratory support upon leaving the delivery room.

methodsA prospective, unblinded, multicenter, cluster-randomized, crossover trial in Australian maternity hospitals comparing initial supplementary oxygen concentrations of 30% and 21% (air) in moderate-late preterm infants who require respiratory support at birth. Eligible infants are those born from 32 + 0 to 35 + 6 weeks' gestation without major cardiorespiratory or craniofacial anomalies, who are receiving active care, and who receive respiratory support in the delivery room commencing within the first three minutes after birth. The primary outcome is the need for ongoing respiratory support upon leaving the delivery room. The trial will recruit a minimum of 1,200 infants from at least 20 study sites in Australia using a waiver of consent process. STATISTICAL ANALYSIS PLAN: To be able to demonstrate an absolute reduction in the primary outcome of 8% (relative reduction 16%), from 51 to 43%, with 80% power and 5% alpha level, a minimum sample of 1200 infants from at least 20 participating sites (20 clusters) with one crossover halfway through each site's total enrolment period is required. The primary outcome, whether the infant is receiving respiratory support when leaving the delivery room, will be analyzed as a binary outcome. The incidence of this outcome will be summarized as the number and percentage in each treatment arm. The treatments will be compared using a risk difference and 95% confidence interval (CI) using individual participant level data. A cross-sectional sample in each treatment period will be modelled with a mixed effects generalized linear model (GLM) with an identity link function and a binomial distribution using an exchangeable correlation structure to model the correlation within each cluster, adjusted for treatment period due to the cross-over nature. The primary analysis will be by intention-to-treat.

trial registrationACTRN12621001267842. Registered on 20th September 2021. Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au ).