Treatment guided by cerebral oximetry in newborns receiving invasive mechanical ventilation: study protocol for step one of the SafeBoosC-IIIv randomised clinical trial.

BACKGROUND: The use of invasive mechanical ventilation in newborns has several risks, including ventilator-induced lung injury, ventilation-associated pneumonia, and hyperventilation leading to potential brain injury, prolonged hospitalisations, and increased mortality. The SafeBoosC-IIIv trial aims to assess the benefits and harms of treatment guided by cerebral oximetry monitoring in newborns receiving invasive mechanical ventilation within the first 28 days from birth. The SafeBoosC consortium is a global network of neonatologists from multiple neonatal intensive care units worldwide.

METHODS: The SafeBoosC-IIIv trial is an investigator-initiated, multinational, randomised, pragmatic, superiority phase III clinical trial. The trial will be conducted in two steps. This is a protocol for step one. The objective of step one is to assess if treatment guided by cerebral oximetry monitoring according to the SafeBoosC treatment guideline compared with usual care in newborns receiving invasive mechanical ventilation increases the number of hospital-free days. The participants will be newborns with a gestational age more than or equal to 28 + 0 weeks, postnatal age less than 28 days, expected to receive invasive mechanical ventilation (intubation) for at least 24 h, and a cerebral oximeter available so monitoring can be started within 6 h after initiation of invasive mechanical ventilation. Exclusion criteria will be suspicion of or confirmed brain injury or congenital heart malformation likely to require surgery. A total of 1,610 participants will be randomised 1:1 to treatment guided by cerebral oximetry monitoring or usual care. The primary outcome will be hospital-free days, and the secondary outcomes will be serious adverse events and invasive mechanical ventilation-free days. All outcomes will be assessed at 90 days after randomisation.

DISCUSSION: The SafeBoosC-IIIv trial has several strengths, including detailed predefined methodology, a high degree of external validity due to centres in several countries, and the trial will be built upon the already established SafeBoosC consortium and the experience from the previous SafeBoosC-II and SafeBoosC-III trials. The SafeBoosC-IIIv trial has limitations, including current lack of funding for step two, lack of blinding of the clinical staff, and the clinicians may have limited experience in using the device.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT05907317, registered 8 June 2023, https://clinicaltrials.gov/study/NCT05907317?cond=NCT05907317&rank=1.