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

Study Overview
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Brief Summary
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The objective of the SafeBoosC-IIIv trial is to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. The hypothesis is that 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.

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

Conditions
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Hypoxia, Infant, Newborn, Diseases

Intervention / Treatment
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* Device: Cerebral oximetry monitoring device
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age more than 28+0 weeks Postnatal age less than 28 days Expected to receive mechanical ventilation for at least 24 hours, as judged by the physician intending to randomise Equipoise as regards the need for cerebral oximetry Parental informed consent unless the centre has chosen to use 'opt-out' or deferred consent as consent method. Exclusion Criteria: No signed parental informed consent (if prior consent is used), or lack of a record that the clinician has explained the trial to the parents and the parents agreed (if 'opt-out' is used,) Suspicion of or confirmed brain injury or disorder (e.g. perinatal asphyxia, cerebral haemorrhage, cerebral malformation, genetic or metabolic disease) A cerebral oximeter is not available Newborns with congenital heart malformations who is likely to need surgery.

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cerebral oximetry + usual care<br> | Device: Cerebral oximetry monitoring device<br>* The experimental group will receive cerebral oximetry added to usual care, if possible before or, as soon as possible and within six hours after mechanical ventilation has been initiated, and continuing until the cardio-pulmonary function has been stabilised as indicated by the need for respiratory and circulatory support and evaluated by the responsible physician, until 28 days after birth, or until death. The devices used are approved for clinical use in newborns and will be used according to the user manuals provided by the manufacturers. Furthermore, all clinical staff will be offered web-based training and certification that covers the principles of cerebral oximetry, practical application, as well as pathophysiology, and relevant interventions in the case of low cerebral oxygenation.<br>Other: Usual care<br>* Usual care offered to newborns in the control group will be offered equally in the experimental group (e.g. antibiotics; nutrition; etc.). There will be no attempt to standardize 'usual care' among centres.<br>|
| Other: Usual care<br>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<br>* Usual care offered to newborns in the control group will be offered equally in the experimental group (e.g. antibiotics; nutrition; etc.). There will be no attempt to standardize 'usual care' among centres.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite of death from any cause or moderate to severe neurodevelopmental disability | There will be two co-primary outcomes, a composite dichotomized outcome and a continuous outcome: 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 | 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 |
| --- | --- | --- |
| Serious adverse events | One or more Serious Adverse Events after randomisation and within the 28 first days of life, i.e. one or more of the following Death from any cause Any brain injury diagnosed by imaging Seizures treated with antiepileptic medicine Necrotising enterocolitis (NEC) Bells grade 2 or more Sepsis (confirmed or suspected infection treated with antibiotics for 5 days or more) Extra Corporal Membrane Oxygenation (ECMO) Renal replacement therapy Use of vasopressor/inotropes Nitric Oxygen treatment On mechanical ventilation at 28 days of life | 28 days | 
| Days alive without mechanical ventilation |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Near-infrared spectroscopy, Randomised clinical trial, Mechanical ventilation