BACKGROUND: The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants' lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. METHODS/DESIGN: SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children's Abilities-Revised (PARCA-R) at 2 years of corrected age. DISCUSSION: There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. TRIAL REGISTRATION: The protocol is registered at www. CLINICALTRIALS: gov (NCT05907317; registered 18 June 2023).

• MeSH
• dítě MeSH
• jednotky intenzivní péče o novorozence MeSH
• kojenec MeSH
• lidé MeSH
• mozek MeSH
• mozkový krevní oběh MeSH
• novorozenec MeSH
• oxymetrie * metody   MeSH
• randomizované kontrolované studie jako téma MeSH
• umělé dýchání * škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

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.

• MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozkový krevní oběh MeSH
• následné studie MeSH
• novorozenci extrémně nezralí * MeSH
• novorozenec MeSH
• oxymetrie metody   MeSH
• poranění mozku * MeSH
• předškolní dítě MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

• MeSH
• bronchopulmonální dysplazie etiologie   MeSH
• kojenec MeSH
• lidé MeSH
• mozkový krevní oběh MeSH
• nekrotizující enterokolitida etiologie   MeSH
• nemoci nedonošenců * diagnóza   mortalita   terapie   MeSH
• novorozenci extrémně nezralí * MeSH
• novorozenec MeSH
• novorozenecká sepse etiologie   MeSH
• oxymetrie * metody   MeSH
• poranění mozku diagnostické zobrazování   etiologie   MeSH
• retinopatie nedonošených etiologie   MeSH
• ultrasonografie MeSH
• velký mozek MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

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.

• MeSH
• blízká infračervená spektroskopie metody   MeSH
• gestační stáří MeSH
• lidé MeSH
• monitorování fyziologických funkcí metody   MeSH
• mozková hypoxie diagnostické zobrazování   prevence a kontrola   MeSH
• novorozenci extrémně nezralí * MeSH
• novorozenec MeSH
• oxymetrie metody   MeSH
• velký mozek diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• pragmatická klinická studie MeSH
• protokol klinické studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses. METHODS/DESIGN: The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis. DISCUSSION: In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis. TRIAL REGISTRATION: ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.

• MeSH
• blízká infračervená spektroskopie přístrojové vybavení   metody   MeSH
• jednotky intenzivní péče o novorozence MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• monitorování fyziologických funkcí přístrojové vybavení   metody   MeSH
• mozek diagnostické zobrazování   metabolismus   patologie   MeSH
• mozková hypoxie diagnóza   epidemiologie   terapie   MeSH
• multicentrické studie jako téma MeSH
• novorozenci extrémně nezralí * MeSH
• novorozenec MeSH
• pragmatické klinické studie jako téma MeSH
• randomizované kontrolované studie jako téma MeSH
• terapie náhlých příhod metody   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• dopisy MeSH

BACKGROUND: Uncertainty about the presence of infection results in unnecessary and prolonged empiric antibiotic treatment of newborns at risk for early-onset sepsis (EOS). This study evaluates the impact of this uncertainty on the diversity in management. METHODS: A web-based survey with questions addressing management of infection risk-adjusted scenarios was performed in Europe, North America, and Australia. Published national guidelines (n = 5) were reviewed and compared with the results of the survey. RESULTS: 439 Clinicians (68% were neonatologists) from 16 countries completed the survey. In the low-risk scenario, 29% would start antibiotic therapy and 26% would not, both groups without laboratory investigations; 45% would start if laboratory markers were abnormal. In the high-risk scenario, 99% would start antibiotic therapy. In the low-risk scenario, 89% would discontinue antibiotic therapy before 72 hours. In the high-risk scenario, 35% would discontinue therapy before 72 hours, 56% would continue therapy for 5-7 days, and 9% for more than 7 days. Laboratory investigations were used in 31% of scenarios for the decision to start, and in 72% for the decision to discontinue antibiotic treatment. National guidelines differ considerably regarding the decision to start in low-risk and regarding the decision to continue therapy in higher risk situations. CONCLUSIONS: There is a broad diversity of clinical practice in management of EOS and a lack of agreement between current guidelines. The results of the survey reflect the diversity of national guidelines. Prospective studies regarding management of neonates at risk of EOS with safety endpoints are needed.

• MeSH
• dodržování směrnic * MeSH
• koordinovaný terapeutický postup * MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecká sepse diagnóza   terapie   MeSH
• průzkumy a dotazníky MeSH
• směrnice jako téma * MeSH
• zdravotní politika MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Austrálie MeSH
• Evropa MeSH
• Severní Amerika MeSH