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 harm in trial participants at 2 years of corrected age. One important challenge is the 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 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 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 2 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. Trial registration: ClinicalTrials.gov NCT05134116 . Registered on 24 November 2021.
Bibliografisk noteFunding Information:
Open access funding provided by Royal Library, Copenhagen University Library The sponsor is a regional public health trust in Denmark, and its representative has been the coordinator of the SafeBoosCproject since its inception in 2009. The sponsor representative and coordinating investigator, Professor of Neonatology Gorm Greisen, is the initiator of the SafeBoosC-III project. He has no financial interest in the results of the trial, nor in the NIRS-devices. The Elsass Foundation, Aage and Johanne Louis-Hansen Foundation, and Svend Andersen Foundation supported the SafeBoosC-III trial through unconditional and unrestricted grants of DKK 3,300,000, DKK 1,000,000, and DKK 1,000,000, respectively. These funding sources had no role in the design of this study and will not have any role during its execution, analysis, interpretation of the data, or decision to submit results. We will seek additional local and central funding. Such sources will not have any influence on the methodology, data, analysis, reporting, or conclusions of the study. Furthermore, any participating department can seek local/national support from all sources, as long such sources will not have any influence on the study.
SafeBoosC-III is led by a Steering Committee comprising the coordinating investigator, the national coordinators, and two representatives from the Copenhagen Trial Unit. The same steering committee will serve for the SafeBoosC-III follow-up study. Decisions will be by a simple majority. The Steering Committee will meet every 6 months or more if necessary. Otherwise, decisions can be made by email. Day-to-day management of the study will be done by the study manager. The sponsor played no part in the study design, collection, management, analysis and interpretation of data, writing of the report, and the decision to submit the report for publication. There was no patient or public involvement in the design of this protocol. The European Foundation for the care of Newborn Infants (EFCNI) was part of an EU application for funding of the SafeBoosC-III trial, but as this failed, and no other funding for their participation could be obtained, they decided to withdraw from the consortium.
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