Higher versus lower nasal continuous positive airway pressure for extubation of extremely preterm infants in Australia (ÉCLAT): a multicentre, randomised, superiority trial.

ABSTRACT

BACKGROUND: Extremely preterm infants often require invasive mechanical ventilation, and clinicians aim to extubate these infants as soon as possible. However, extubation failure occurs in up to 60% of extremely preterm infants and is associated with increased mortality and morbidity. Nasal continuous positive airway pressure (nCPAP) is the most common post-extubation respiratory support, but there is no consensus on the optimal nCPAP level to safely avoid extubation failure in extremely preterm infants. We aimed to determine if higher nCPAP levels compared with standard nCPAP levels would decrease rates of extubation failure in extremely preterm infants within 7 days of their first extubation. METHODS: In this multicentre, randomised, open-label controlled trial done at three tertiary perinatal centres in Australia, we assigned extremely preterm infants to extubation to either higher nCPAP (10 cmH2O) or standard nCPAP (7 cmH2O). Infants were eligible if they were born at less than 28 weeks' gestation, were receiving mechanical ventilation via an endotracheal tube, and were being extubated for the first time to nCPAP. Eligible infants must have received previous treatment with exogenous surfactant and caffeine. Infants were ineligible if they were planned to be extubated to a mode of respiratory support other than nCPAP, if they had a known major congenital anomaly that might affect breathing, or if ongoing intensive care was not being provided. Parents or guardians provided prospective, written, informed consent. Infants were maintained within an assigned nCPAP range for a minimum of 24 h after extubation (higher nCPAP group 9-11 cmH2O and standard nCPAP group 6-8 cmH2O). Randomisation was stratified by both gestation (22-25 completed weeks or 26-27 completed weeks) and recruiting centre. The primary outcome was extubation failure within 7 days and analysis was by intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12618001638224. FINDINGS: Between March 3, 2019, and July 31, 2022, 483 infants were born at less than 28 weeks and admitted to the recruiting centres. 92 infants were not eligible, 172 were not approached, 65 families declined to participate, and 15 consented but were not randomly assigned. 139 infants were enrolled and randomly assigned, 70 to the higher nCPAP group and 69 to the standard nCPAP group. One infant in the higher nCPAP group was excluded from the analysis because consent was withdrawn after randomisation. 104 (75%) of 138 mothers were White. The mean gestation was 25·7 weeks (SD 1·3) and the mean birthweight was 777 grams (201). 70 (51%) of 138 infants were female. Extubation failure occurred in 24 (35%) of 69 infants in the higher nCPAP group and in 39 (57%) of 69 infants in the standard nCPAP group (risk difference -21·7%, 95% CI -38·5% to -3·7%). There were no significant differences in rates of adverse events between groups during the primary outcome period. Three patients died (two in the higher nCPAP group and one in the standard nCPAP group), pneumothorax occurred in one patient from each group, spontaneous intestinal perforation in three patients (two in the higher nCPAP group and one in the standard nCPAP group) and there were no events of pulmonary interstitial emphysema. INTERPRETATION: Extubation of extremely preterm infants to higher nCPAP significantly reduced extubation failure compared with extubation to standard nCPAP, without increasing rates of adverse effects. Future larger trials are essential to confirm these findings in terms of both efficacy and safety. FUNDING: National Health and Medical Research Council Centre for Research Excellence in Newborn Medicine, number 1153176.