Newborn infants in need of mechanical ventilation are at high risk of a detrimental outcome, not only due to the underlying condition, but also due to complications from the mechanical ventilation itself. Such complications include pneumothorax, ventilation associated pneumonia, and hyperventilation causing vasoconstriction of the cerebral vasculature and possibly brain ischaemia. Summary data on outcomes are not easily available, but during 2019 death before discharge occurred in 41/500 (8.2%) newborns, born at more than 28 weeks of gestation and in need of mechanical ventilation during the neonatal period, in 10 neonatal units within the SafeBoosC-III consortium. A meta-analysis including 895 neonates from 23 non-randomised studies, undergoing surgery for non-cardiac congenital anomalies, also found a deficit in intelligence quotient of 0.5 standard deviations below the population average (Stolwijk LJ et al, Pediatrics 2016). Additionally, data from a Danish national cohort showed that 18% of children who underwent mechanical ventilation in the neonatal period, needed special educational support in primary school, which is 2.5 times more often than normal (Wiingreen et al. unpublised data).
Thus, mechanically ventilated newborns are a high-risk population. Given the instability of the newborn’s pulmonary and circulatory physiology, it is possible that the addition of measuring the oxygenation of the brain, by non-invasive near-infrared light technology (cerebral oximetry) plus a treatment guideline, as an addition to the complex treatment and monitoring regimes for these newborns, may increase the chance of surviving without neurodevelopmental impairment.
SafeBoosC-IIIv will be an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. The trial will be conducted in two steps. In step 1, 1,610 newborns will be randomised, and the outcomes will be assessed 90 days after randomisation. Funding has been obtained for step 1 from the Independent Research Fund Denmark. If further funding is obtained, we will continue to include newborns until a total of 3,000 newborns are randomised and follow them up at 2 years after randomisation (step 2). Randomisation will be performed across several neonatal intensive care units in Africa, Asia, Australia, Europe, North America, and South America.
The objective of the SafeBoosC-IIIv trial is to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. The hypothesis for step 1 is that the intervention will increase the number of hospital-free days within 90 days of randomisation. The hypothesis for step 2 is that the intervention will decrease a composite outcome of death or moderate to severe neurodevelopmental disability and/or increase the mean PARCA-R non-verbal cognitive score at two years of corrected age.
The first infant was randomised in April 2025. More than 70 neonatal intensive care units across the world have initiated the trial preparations.
The progress in each unit can be followed on the trial preparation log.
Please contact the trial manager (Caroline Kamp, caroline.kamp@ctu.dk) if you wish to be involved in the SafeBoosC-IIIv trial.