Hypoxia, Infant, Newborn, Diseases
Conditions
Keywords
Near-infrared spectroscopy, Randomised clinical trial, Mechanical ventilation
Brief summary
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.
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).
Interventions
DEVICECerebral 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.
OTHERUsual care
Treatment as usual
Sponsors
Copenhagen Trial Unit, Center for Clinical Intervention Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Step one: The primary outcome will be assessed by a blinded investigator. The principal investigator from each centre must develop a local blinding procedure, describing how blinding is achieved. To support the principal investigators in this work, a Standard Operation Procedure with suggestions for blinding procedures will be developed. Data managers, statisticians, and conclusion drawers will be blinded. Step two: Due to the nature of the experimental intervention, clinical staff and the parents will not be blinded to group allocation. Thus, the primary outcome will not be blinded in cases when it relies on parental reporting. If there is no contact with the parents, or if they do not return the questionnaire, data will be collected from health care records. Investigators reviewing the health care records will, if possible, be blinded to the allocated intervention. Data managers, statisticians, and conclusion drawers will be blinded.
Intervention model description
The trial will recruit 1610 babies in step one. Randomisation will continue until 3000 babies are recruited in step two.
Eligibility
Sex/Gender
ALL
Age
0 Days to 28 Days
Healthy volunteers
No
Inclusion criteria
* Gestational age more than or equal to 28+0 * Postnatal age less than 28 days * Expected to receive invasive mechanical ventilation (intubation) 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 * 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. severe hypoxic-ischemic encephalopathy, intraventricular haemorrhage grade 3 or 4, cerebral malformation, genetic or metabolic disease) * Suspicion or diagnosis of congenital heart malformations likely to require surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital-free days within 90 days of randomisation | 90 days | Primary outcome for step one |
| A composite of death from any cause or moderate to severe neurodevelopmental disability | 2 years | 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 1. cerebral palsy with Global Motor Function Classification System level 2 or higher; 2. 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); 3. hearing loss corrected with aids or worse; or 4. 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. |
| Parental questionnaires | 18-30 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with a serious adverse event | 90 days | 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 |
| Invasive mechanical ventilation-free days within 90 days of randomisation | 90 days | Secondary outcome for step one |
Other
| Measure | Time frame | Description |
|---|---|---|
| Late onset sepsis | 90 days | Exploratory outcome for step one |
| Use of daily medication | 2 years | Exploratory outcome for step two: Use of medication during the last two months, at two years of corrected age. |
| Invasive mechanical ventilation-related infection | 90 days | Exploratory outcome for step one |
| Cerebral palsy | 2 years | Exploratory outcome for step two: defined as Global Motor Function Classification System level 2 or above, at two years of corrected age. |
| Sensory deficit | 2 years | exploratory outcome for step two: defined as any degree of vision or hearing impairment, at two years of corrected age. |
| All-cause mortality | 2 years | Exploratory outcome for step two: Mortality at two years of corrected age. |
Countries
Spain
Contacts
Primary ContactCaroline Kamp, PhD
Backup ContactJohanne Juul Petersen
Outcome results
None listed