SafeBoosC-IIIv: pragmatic RCT in newborns undergoing mechanical ventilation

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 is 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.

The objective of the SafeBoosC-IIIv trial is to evaluate the effects of adding cerebral oximetry to usual care versus usual care in mechanically ventilated newborns. The hypothesis 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 trial will be an investigator-initiated, open-label, multinational, randomised, pragmatic phase III clinical trial. A total of 3000 newborns will be randomised in 90 neonatal intensive care units across 18 countries.

As of September 2021, the protocol is being finalised. The next step is to obtain ethics approval in Denmark and publish the protocol in an international peer-reviewed journal, as a design paper. Additionally, the process of extending the SafeBoosC-III consortium, in order to increase the number of recruiting neonatal intensive care units from 72 to 90, is ongoing. Funding applications to cover central trial costs has also been sent to the Novo Nordisk Foundation (expected answer in December 2021). 

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