Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants. A protocol for the SafeBoosC phase III randomized clinical trial

Background Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC-III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants. Methods/Design SafeBoosC III is an investigator-initiated multinational randomized, pragmatic phase III clinical trial. It is open label, but parts will be conducted blinded to intervention. Inclusion criteria consists of infants born below 28 weeks postmenstrual age and parental informed consent (unless the site has is using ‘opt-out’ or deferred consent). Exclusion criteria consists of missing parental informed consent (or if ‘opt-out’ is used, lack of record that clinical staff have explained the trial and the ‘opt-out’ consent process to parents and/or a record in the infant’s clinical file of parents’ decision to opt-out); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 hours after birth. Participants will be randomized 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 hours of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36 weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36 weeks postmenstrual age. To detect a 22% relative risk difference between the experimental and control group, we intend to randomize a cohort of 1600 infant. Discussion Treatment guided by cerebral NIRS oximetry has the potential to decrease risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates.