BACKGROUND: Cerebral 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/DESIGN: SafeBoosC 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. DISCUSSION: Treatment 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 REGISTRATION: ClinicalTrial.gov, NCT03770741. Registered 10 December 2018.

Copenhagen Trial Unit Rigshospitalet Blegdamsvej 9 2100 Copenhagen Denmark

Department of Cardiology Holbæk Hospital Smedelundsgade 60 4300 Holbæk Denmark

Department of Clinical Sciences and Community Health University of Milan Via Francesco Sforza 35 20122 Milan Italy

Department of Intensive Care Rigshospitalet Blegdamsvej 9 2100 Copenhagen Denmark

Department of Neonatology Centro hospitalar Universitário de São João Alameda Prof Hernâni Monteiro 4200 319 Porto Portugal

Department of Neonatology Children's Hospital of Fudan University 399 Wanyuan Rd Minhang Qu Shanghai Shi China

Department of Neonatology Children's University Hospital of Zürich Steinweisstrasse 75 8037 Zurich Switzerland

Department of Neonatology Gazi University Hospital Emniyet Mahallesi Gazeteci Yazar Muammer Yaşar Bostancı Sokak 06560 Yenimahalle Ankara Turkey

Department of Neonatology Hospices Civil De Lyon 3 Quai des Célestins 69002 Lyon France

Department of Neonatology La Paz University Hospital Paseo De La Castellana 261 28046 Madrid Spain

Department of Neonatology Oslo University Hospital Kirkeveien 166 0450 Oslo Norway

Department of Neonatology Poznan University of Medical Sciences Polna 33 60 535 Poznań Poland

Department of Neonatology Rigshospitalet Blegdamsvej 9 2100 Copenhagen Denmark

Department of Neonatology Royal Hospital for Children 1345 Govan Rd Glasgow G51 4TF UK

Department of Neonatology University Children's Hospital Tuebingen Hoppe Seyler Straße 1 72076 Tuebingen Germany

Department of Neonatology University Hospital Leuven Herestraat 49 Leuven Belgium

Department of Neonatology University Hospital Motol 5 Uvalu 84 150 06 Prague 5 Czech Republic

Department of Neonatology Wilhelmina Children's Hospital Lundlaan 6 3584 EA Utrecht Netherlands

Department of Pediatrics Medical University of Graz Auenbruggerplatz 30 Graz Austria

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

Division of Newborn Medicine Hackensack Meridian Health Mountainside Medical Center 1 Bay Ave Montclair NJ USA

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Via della Commenda 12 IT 20122 Milan Italy

Infant Centre and Department of Paediatrics and Child Health University College Cork College Road Cork Ireland

Neonatal Intensive Care Unit Cambridge University Hospitals NHS Foundation Trust Hills Road Cambridge CB2 0SW UK

NICU Department of Pediatrics University General Hospital of Patras 265 04 Patras Greece

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ClinicalTrials.gov
NCT03770741