Background The SafeBoosC-III trial investigated treatment guided by cerebral oximetry monitoring for the first 72 hours after birth in extremely preterm infants and showed no effects on mortality or severe brain injury at 36 weeks’ postmenstrual age versus usual care. As severe brain injury in the neonatal period is not a strong predictor of long-term neurodevelopmental outcomes, the SafeBoosC-III follow-up study aims to assess the long-term benefits and harms of the experimental intervention versus usual care at two years of corrected age. This detailed statistical analysis plan outlines our approach for analysing outcomes in the SafeBoosC-III follow-up study.

Methods The co-primary outcomes are 1) a composite of death or moderate-to-severe neurodevelopmental disability and 2) the mean Bayley-III/IV cognitive score. We will employ a 3-tier data model, incorporating routine clinical follow-up, parental questionnaires, and informal assessments to minimize missing data. All randomised participants with available data will be included in all analyses. Mixed-effect linear and logistic regression will be used to analyse the dichotomous and continuous co-primary outcomes, respectively. Sensitivity analyses will be conducted to address missing data and assess the robustness of our findings.

Discussion The statistical analysis plan aims to ensure transparency and reduce the risk of outcome reporting bias. By including dichotomous and continuous co-primary outcomes, we aim to provide a comprehensive evaluation of the intervention’s effect on long-term benefits and harms.

The authors have declared no competing interest.

https://safeboosc.eu/

Funding The sponsor/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 1,950,000 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 get 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 get any influence on the study.

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↵† Sponsor: The Capital Region, Department of Neonatology 5024, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Gorm Greisen, phone: +45 3545 1326, e-mail: gorm.greisenregionh.dk

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