BACKGROUND: Newborns requiring invasive mechanical ventilation are at high risk of neurodevelopmental impairment, prolonged hospitalisation, and increased mortality. Treatment guided by cerebral oximetry monitoring has been proposed to reduce morbidity and mortality. METHODS: The SafeBoosC-IIIv trial is a multicentre, parallel-group, randomised clinical trial. The trial will be conducted in two steps. This is a statistical analysis plan for step one. The objective of step one is to assess whether treatment guided by cerebral oximetry monitoring, compared with usual care, increases the number of hospital-free days in newborns receiving invasive mechanical ventilation. Inclusion criteria are gestational age ≥ 28 + 0 weeks, postnatal age less than 28 days, expected to receive invasive mechanical ventilation (intubation) for at least 24 h, and a cerebral oximeter available so monitoring can be started within 6 h after initiation of invasive mechanical ventilation. Exclusion criteria are suspicion of or confirmed brain injury or congenital heart malformation likely to require surgery. A total of 1610 participants will be randomised 1:1 to treatment guided by cerebral oximetry monitoring or usual care. The primary outcome will be hospital-free days within 90 days of randomisation, which will be analysed with the van Elteren test stratified by 'centre'. This statistical analysis plan provides a detailed description of the planned analyses, including methods for handling missing data and assessing statistical assumptions. Analyses will follow the intention-to-treat principle and will be performed independently by two statisticians. CONCLUSION: This statistical analysis plan describes the planned statistical analyses in detail for step one of the SafeBoosC-IIIv trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05907317. First submitted on 8 June 2023, https://clinicaltrials.gov/study/NCT05907317 .

2 Department of Neonatology Neonatal Biophysical Monitoring and Cardiopulmonary Therapies Research Unit Poznan University of Medical Sciences Poznan Poland

Centre for Clinical Intervention Research Copenhagen Trial Unit The Capital Region of Denmark Copenhagen Denmark

CHU Nîmes Nîmes France

Department of Health Research Methods Evidence and Impact McMaster University Hamilton Canada

Department of Neonatology and Intensive Care University Children's Hospital Zürich Zurich Switzerland

Department of Neonatology Clinical County Emergency Hospital Sibiu Sibiu Romania

Department of Neonatology Copenhagen Denmark

Department of Neonatology Health Sciences University Basaksehir Cam and Sakura City Hospital İstanbul Türkiye

Department of Neonatology Hospital Clínic Barcelona BCNatal Barcelona Center for Maternal Fetal and Neonatal Medicine Barcelona Spain

Department of Neonatology La Paz University Hospital Hospital La Paz Institute for Health Research IdIPAZ Madrid Spain

Department of Neuroanaesthesiology Neuroscience Centre The Capital Region Copenhagen Denmark

Department of Pediatrics 2 Medical University of Innsbruck Innsbruck Austria

Department of Pediatrics School of Medicine Pontificia Universidad Catolica de Chile Santiago Chile

Department of Pediatrics University of Alberta Edmonton Canada

Department of Regional Health Research The Faculty of Health Sciences University of Southern Denmark Odense Denmark

Division of Neonatology Department of Pediatrics and Adolescence Medicine Medical University Graz Graz Austria

Faculty of Medicine Lucian Blaga University Sibiu Sibiu Romania

Grace Centre for Newborn Intensive Care in The Children's Hospital at Westmead Sydney Australia

Hospital Clinico San Carlos IdISSC Madrid Spain

Hospital de Clínicas de Porto Alegre Universidade Federal Do Rio Grande Do Sul Porto Alegre Brazil

Hospital Universitario 12 de Octubre Madrid Spain

Hospital Universitario Austral Pilar Argentina

Hospital Universitario Puerta del Mar Cádiz Spain

Hospital Universitario Virgen Las Nieves Granada Spain

Infant Research Centre University College Cork Cork Ireland

Institute of Clinical Medicine University of Copenhagen Copenhagen Denmark

Ippokrateion General Hospital of Thessaloniki Thessaloniki Greece

Medical Center University of Freiburg Freiburg Germany

National Health Commission Key Laboratory of Neonatal Diseases Children's Hospital of Fudan University Shanghai China

NHMRC Clinical Trials Centre University of Sydney Sydney Australia

Red de Salud UC Christus Santiago Chile

St John's Medical College Hospital Bengaluru Karnataka India

The National Institute for Mother and Child Care Alessandrescu Rusescu Polizu Maternity București Romania

University Hospital Leuven Louvain Belgium

University Hospital Motol Prague Czech Republic

University Hospital of Heraklion Heraklion Greece

University of Patras General Hospital Rio Greece

UT Southwestern Medical Center Dallas USA

Women and Newborn Hospital University Teaching Hospitals Lusaka Zambia

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Treatment guided by cerebral oximetry in mechanically ventilated newborns: a statistical analysis plan for step one of the SafeBoosC-IIIv randomised clinical trial

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ClinicalTrials.gov
NCT05907317