Cerebral oximetry monitoring versus usual care for extremely preterm infants: a study protocol for the two-year follow up of the SafeBoosC-III randomised clinical trial

Abstract

Background: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks’ postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability or any harms in trial participants at two years of corrected age. One important challenge is lack of funding for local costs for a trial-specific assessment. Methods: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks’ postmenstrual age and will potentially be available for the two-year follow up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up studyand parental consent if required by local regulations. We aim to collect data from routine follow up programs between the age of 18 to 30 months of corrected age. If no routine follow up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children’s Abilities - Revised. There will be two co-primary outcomes: the composite of death or moderate-or-severe neurodevelopmental disability; and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss-to-follow up assuming that little data is better than no data at all. Discussion: Follow up at the age of two years is important for intervention trials in the newborn period as only time can show real benefits and harms later in childhood. To decrease the risk of generalisation and data driven biased conclusions, we present a detailed description of the methodology for the SafeBoosC-III follow up study. As funding is limited, a pragmatic approach is necessary. Study registration: ClinicalTrial.gov NCT05134116 (registered 24-11 2021), https://clinicaltrials.gov/ct2/show/NCT05134116?term=safeboosc&draw=2&rank=2 Protocol version 1 (1st of May 2023)