Clinical Trial
Main Goals and Outcome Variables
The proposed observer-blinded randomized controlled trial was designed and will be powered to compare the effect of closed-loop automated control of FiO2 in addition to manual adjustments, in comparison with manual adjustments of FiO2 only, on death and severe complications of prematurity thought to be related to hypoxia/hyperoxia and neurodevelopmental impairment in ELGANs. It will also provide insight into the safety and efficacy of FiO2-C during mechanical ventilation and continuous positive airway pressure (CPAP).
For assessment of safety, the incidence of relevant complications of prematurity that are not evaluated as outcomes (patent ductus arteriosus, periventricular leukomalacia, sepsis, etc.) and of all adverse events will be monitored and reported during the study.
For asessment of efficacy, the primary outcome variable will be assessed as a composite of any of the following:
- Death
- Severe retinopathy of prematurity
- Chronic lung disease of prematurity (BPD)
- Necrotizing enterocolitis (NEC)
The co-primary outcome (evaluated according to a hierarchical test design) is a composite of death or neurodevelopmental impairment (motor disability (GMFCS 2-5), language or cognitive delay (language score < 85 or cognitive score < 85 on Bayley Scales of Infant Development, 3rd edition), or severe visual or hearing impairment (need for a hearing aid or cochlear implant)) at 24 months corrected age.
The Study Population
2340 Patients will be recruited in approximately 50-100 tertiary care neonatal centers in Germany and the European Union. It is estimated that the recruitment phase of the study will last for 36 months.
Inclusion criteria:
- GA at birth 23+0/7 to 27+6/7 weeks
Exclusion criteria:
- Decision not to provide full life support / decision for palliative care only before study entry
- Severe congenital abnormalities (particularly those affecting respiratory, cardiovascular, or gastrointestinal function or long-term neuro-cognitive development, whereas a patent ductus arteriosus or a PFO/ASDII is not considered a congenital anomaly in preterm infants)
- Postnatal age >48h
- Missing parental consent
- Lack of device enabling closed-loop automatic control of FiO2 before randomization