Safeguarding the Brain of Our Smallest Children-IIIv (SafeBoosC-IIIv) (SafeBoosC-IIIv)

Safeguarding the Brain of Our Smallest Children-IIIv (SafeBoosC-IIIv): Cerebral Oximetry Versus Usual Care in Mechanically Ventilated Newborns

The objective of the SafeBoosC-IIIv trial is to assess benefits and harms of cerebral oximetry in newborns receiving invasive mechanical ventilation. The hypothesis is that:

i. Cerebral oximetry added to usual care versus usual care alone in newborns receiving invasive mechanical ventilation will increase the number of hospital-free days within 90 days of randomisation.

ii. The intervention will decrease a composite outcome of death or moderate to severe neurodevelopmental disability and/or increase the mean PARCA-R non-verbal cognitive score at two years of corrected age.

Study Overview

• Status: Not yet recruiting
• Conditions: Infant, Newborn, Diseases; Hypoxia
• Intervention / Treatment: Other: Usual care; Device: Cerebral oximetry monitoring device

Detailed Description

SafeBoosC-IIIv will be an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. The trial will be conducted in two steps. In step one, 1,610 newborns will be randomised, and the outcomes will be assessed 90 days after randomisation. Funding has been obtained for step one. If further funding is obtained, we will continue to include newborns until a total of 3,000 newborns are randomised and then follow them up at two years of corrected age (step two).

• Study Type: Interventional
• Enrollment (Estimated): 1610
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Gestational age more than or equal to 28+0
• Postnatal age less than 28 days
• Expected to receive mechanical ventilation (invasive, i.e., not including CPAP or BiPAP) for at least 24 hours, as judged by the physician intending to randomise
• Parental informed consent unless the centre has chosen to use 'opt-out' or deferred consent as consent method and a cerebral oximeter available so monitoring can be started within six hours after initiation of invasive mechanical ventilation

Exclusion Criteria:

• Suspicion of or confirmed brain injury or disorder (e.g. perinatal asphyxia, cerebral haemorrhage, cerebral malformation, genetic or metabolic disease)
• Suspicion or diagnosis of congenital heart malformations likely to require surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cerebral oximetry + usual care	Other: Usual care; Treatment as usual; Device: Cerebral oximetry monitoring device; Participants in the experimental group will be monitored with cerebral oximetry, if possible before or, as soon as possible and within six hours after initiation of invasive mechanical ventilation. Cerebral oximetry will be continued until 1) the cardio-pulmonary function has been stabilised as indicated by the need for respiratory and circulatory support and evaluated by the responsible physician, 2) extubation, 3) until 28 days after birth, or 4) until death. Randomisation will only direct the use of cerebral oximetry during the first invasive mechanical ventilation episode. Cerebral oximetry will be used to minimise cerebral hypoxia by modifying clinical care according to the SafeBoosC treatment guideline and monitoring as usual.
Other: Usual care; The control group will receive mechanical ventilation without access to cerebral oximetry and the SafeBoosC treatment guideline. If the newborn is cared for outside the neonatal unit at any time, e.g. during surgery, cerebral oximetry may or may not be used, as decided by the responsible physician there	Other: Usual care; Treatment as usual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital-free days within 90 days of randomisation	Primary outcome for step one	90 days
A composite of death from any cause or moderate to severe neurodevelopmental disability	Co-primary outcome for step two A composite of death from any cause or moderate to severe neurodevelopmental disability at two years of corrected age. Moderate to severe neurodevelopmental disability will be defined as one or more of the following; cerebral palsy with Global Motor Function Classification System level 2 or higher;; a Parent Report of Children's Abilities-Revised (PARCA-R) non-verbal cognitive function score (range 0-34, higher score means better outcome) below -2 standard deviations (SD);; hearing loss corrected with aids or worse; or; vision impairment defined as moderately reduced vision of one eye, or only being able to perceive light or light reflecting objects; or blind in one eye with good vision in the contralateral eye.	2 years
Parental questionnaires	Co-primary outcome for step two: Parental questionnaires completed between 18-30 months' corrected age as well as available data from at least 12 months' corrected age from health care records, including standardised neurodevelopmental assessments, will be used to assess mortality and neurodevelopment. • Non-verbal cognitive score of Parent Report of Children's Abilities-Revised (PARCA-R), a parental questionnaire, at two years of corrected age (range 0-34, higher score means better outcome).	18-30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a serious adverse event	Secondary outcome for step one: Proportion of participants with one or more Serious Adverse Events within the 90 days of randomization, i.e. one or more of the following: Death from any cause Bronchopulmonary dysplasia (BPD) Any brain injury diagnosed by imaging Seizures treated with antiepileptic medicine Haemodynamic insufficiency that needs cardiovascular support Spontaneous bowel perforation or necrotising enterocolitis (NEC) Bells grade 2 or more Nosocomial infection Extra Corporal Membrane Oxygenation (ECMO) Renal replacement therapy	90 days
Invasive mechanical ventilation-free days within 90 days of randomisation	Secondary outcome for step one	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late onset sepsis	Exploratory outcome for step one	90 days
Invasive mechanical ventilation-related infection	Exploratory outcome for step one	90 days
Cerebral palsy	Exploratory outcome for step two: defined as Global Motor Function Classification System level 2 or above, at two years of corrected age.	2 years
Sensory deficit	exploratory outcome for step two: defined as any degree of vision or hearing impairment, at two years of corrected age.	2 years
All-cause mortality	Exploratory outcome for step two: Mortality at two years of corrected age.	2 years
Use of daily medication	Exploratory outcome for step two: Use of medication during the last two months, at two years of corrected age.	2 years

Collaborators and Investigators

• Sponsor: Copenhagen Trial Unit, Center for Clinical Intervention Research

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: June 8, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Mechanical ventilation; Randomised clinical trial; Near-infrared spectroscopy
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia; Infant, Newborn, Diseases
• Other Study ID Numbers: SafeBoosC-IIIv

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No