Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants: a protocol for the SafeBoosC randomised clinical phase III trial

Abstract

BackgroundCerebral 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/designSafeBoosC III is an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28 weeks postmenstrual age and parental informed consent (unless the site is using ‘opt-out’ or deferred consent). Exclusion criteria will be no parental informed consent (or if ‘opt-out’ is used, lack of a record that clinical staff have explained the trial and the ‘opt-out’ consent process to parents and/or a record of the parents’ decision to opt-out in the infant’s clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 h after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 h 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. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants.DiscussionTreatment guided by cerebral NIRS oximetry has the potential to decrease the 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.Trial registrationClinicalTrial.gov, NCT03770741. Registered 10 December 2018.

Association between early cerebral oxygenation and neurodevelopmental impairment or death in premature infants

“…It remains unclear whether we can improve neurodevelopmental outcomes of preterm infants by intervening on a low StO 2 . Current efforts to intervene on low StO 2 include the SafeBoosc III trial, which plans to determine whether intervening on a low NIRS can reduce risk of death or severe brain injury [15]. The study was designed to use saturation targets based on values from the INVOS device but will allow for the use of the FORESITE elite at the cutoff level of 67 for cerebral hypoxia.…”

Cerebral Oxygenation in Preterm Infants With Necrotizing Enterocolitis

“…It did demonstrate a significant reduction in cerebral oxygenation out of normal range in the experimental group, but no consistent differences were reported in neonatal morbidities or mortality at term equivalent. The SafeBoosC-III trial is currently ongoing exploring whether treatment based on NIRS monitoring for extreme preterm infants during the first 72 hours of life will result in reduction in severe brain injury or death at 36 weeks postmenstrual age 41 .…”

Extremely preterm infant admissions within the SafeBoosC-III consortium during the COVID-19 lockdown

“…Thus, many trials have slowed down, been suspended, or even terminated, due to the difficulties of conducting research under lockdown conditions (7). The SafeBoosC-III trial investigates the benefit and harms of treatment guided by cerebral near-infrared spectroscopy monitoring compared with treatment and monitoring as usual in extremely preterm infants (8). Despite having a vulnerable population, potentially at increased risk of complications to a COVID-19 infection, the trial was able to proceed in most countries.…”

“…This is a retrospective, observational study, based on the NICUs in the consortium of the SafeBoosC-III randomised clinical trial(8). The principal investigators from all of the 79 NICUs in…”

“…Number of randomisations per month within each NICU actively randomising infants in the SafeBoosC-III trial during the last nine months.This is a retrospective, observational study, based on the NICUs in the consortium of the SafeBoosC-III randomised clinical trial(8). The principal investigators from all of the 79 NICUs in the consortium, were invited to participate in this study by e-mail and asked to report the following information: 1) the number of EP infants admitted to their NICU within the three months, where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, 2) the number of EP infants admitted within the corresponding three months of 2019, and 3) the level of restrictions imposed upon the public, during the most rigorous three months of the lockdown period, in a Likert scale format from one to five.…”