Cerebral oximetry monitoring versus usual care for extremely preterm infants: a study protocol for the 2-year follow-up of the SafeBoosC-III randomised clinical trial
Marie Isabel Rasmussen,
Mathias Lühr Hansen,
Adelina Pellicer,
Christian Gluud,
Eugene Dempsey,
Jonathan Mintzer,
Simon Hyttel-Sørensen,
Anne Marie Heuchan,
Cornelia Hagmann,
Ebru Ergenekon,
Gabriel Dimitriou,
Gerhard Pichler,
Gunnar Naulaers,
Guoqiang Cheng,
Jakub Tkaczyk,
Hans Fuchs,
Monica Fumagalli,
Saudamini Nesargi,
Siv Fredly,
Tomasz Szczapa,
Anne Mette Plomgaard,
Bo Mølholm Hansen,
Janus Christian Jakobsen,
Gorm Greisen
Affiliations
Marie Isabel Rasmussen
Department of Neonatology, Copenhagen University Hospital - Rigshospitalet
Mathias Lühr Hansen
Department of Neonatology, Copenhagen University Hospital - Rigshospitalet
Adelina Pellicer
Department of Neonatology, La Paz University Hospital
Christian Gluud
Centre for Clinical Intervention Research, Copenhagen Trial Unit, The Capital Region, Copenhagen University Hospital - Rigshospitalet
Eugene Dempsey
Infant Research Centre and Department of Paediatrics and Child Health, University College Cork
Jonathan Mintzer
Department of Pediatrics, Division of Newborn Medicine, Mountainside Medical Center
Simon Hyttel-Sørensen
Department of Intensive Care, Copenhagen University Hospital – Rigshospitalet
Anne Marie Heuchan
Department of Neonatology, Royal Hospital for Children
Cornelia Hagmann
Department of Neonatology, Children’s University Hospital of Zürich
Ebru Ergenekon
Department of Neonatology, Gazi University Hospital
Gabriel Dimitriou
Department of Pediatrics, NICU, University General Hospital of Patras
Gerhard Pichler
Department of Pediatrics, Medical University of Graz
Gunnar Naulaers
Department of Neonatology, University Hospital Leuven
Guoqiang Cheng
Department of Neonatology, Children’s Hospital of Fudan University
Jakub Tkaczyk
Department of Neonatology, University Hospital Motol
Hans Fuchs
Division of Neonatology and Pediatric Intensive Care Medicine, Center for Pediatrics and Adolescents Medicine, Medical Center, University of Freiburg
Monica Fumagalli
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan
Saudamini Nesargi
St. Johns Medical College Hospital
Siv Fredly
Department of Neonatology, Oslo University Hospital
Tomasz Szczapa
II Department of Neonatology, Poznan University of Medical Sciences
Anne Mette Plomgaard
Department of Pediatrics, Copenhagen University Hospital
Bo Mølholm Hansen
Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital
Janus Christian Jakobsen
Centre for Clinical Intervention Research, Copenhagen Trial Unit, The Capital Region, Copenhagen University Hospital - Rigshospitalet
Gorm Greisen
Department of Neonatology, Copenhagen University Hospital - Rigshospitalet
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 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.
