Safeguarding the brain of our smallest children ;* an investigator-initiated randomised, blinded, multinational, phase II
feasibility clinical trial on near-infrared spectroscopy monitoring
combined with defined treatment guidelines versus
standard monitoring and treatment as usual in premature infants

25,000 infants are born extremely preterm every year in Europe. This group of
infants carries a high risk of death and subsequent cerebral impairment for the
infant, especially in the first 72 hours of life. Mortality is about 20%, and
about 25% of survivors live with either cerebral palsy or low intelligence
quotient. Preventative measures are keys to reducing mortality and morbidity in
this population. There is evidence that the cerebral oxygenation time spent out
of range (time with hypoxia or hyperoxia) is associated with poor outcome in
infants. Near-infrared spectroscopy (NIRS) has been used to monitor tissue
oxygenation since the mid-1980s, and quantification of oxygenation in a
percentage from 0 to 100% has been possible for 10 years. Still, there are no
clinical trials and thus no solid evidence of the clinical utility of NIRS in
preterm infants. Thus, research on the benefits and harms of cerebral
monitoring using NIRS as a part of clinical management of premature infants is
much needed. This study is , anticipatory on a large multi-center trial, a
feasability trail in which 150 patient from 12 European neonatal centers will
be included.

The primary objective of the SafeBoosC trial is to examine if it is possible to
stabilise the cerebral oxygenation of extremely preterm infants (gestational
age < 28 wks) during the first 72 hours of life through the application of
cerebral NIRS oximetry and implementation of a set of defined clinical
treatment guidelines (Appendix A protocol). We hypothesise that by using the
specified treatment guidelines to respond to cerebral monitoring readings
outside the target range, we would reduce the burden of hypo- and hyperoxia and
consequently reduce brain injury.

Preterm infants with a gestational age < 28 weeks will be randomised into one
of two groups (experimental or control) after parental informed consent. Common
is that both groups will have a cerebral oximeter monitoring device placed
within three hours after birth.In the experimental group, the cerebral
oxygenation reading is visible, and the infant will be treated accordingly
using a defined treatment guideline (Appendix A). In the control group, the
cerebral oxygenation reading is NOT visible, and the infant will be treated as
usual. 150 infants from 12 European neonatal units will be included in these
phase II feasibility trial.
Cerebral monitoring with NIRS (standard care on our unit) will start within
three hours of age and the study will last until 72 hours after birth, as these
are the most critical. Each neonate will be followed up until (regular cranial
ultrasound) and at the term equivalent age (advanced MRI) date (approximately
after 3 months) and 24 months after the term equivalent age (Bayley Scales of
Infant Development III (BSIDIII). During the first 72 hours of life also
amplitude integrated EEG (aEEG; standard care on our unit) and at 6 and 64
hours after birth 1ml of blood and urine will be collected for determing levels
of cerebral biomarkers (brain fatty acid binding protein; neurketal and
S100beta).

The premature infants will be randomised into one of two groups (experimental
or control). Common is that both groups will have a cerebral oximeter
monitoring device placed within three hours after birth. In the experimental
group, the cerebral oxygenation reading is visible, and the infant will be
treated accordingly using a defined treatment guideline (Appendix A protocol) .
In the control group, the cerebral oxygenation reading is NOT visible, and the
infant will be treated as usual.

The risks for participants are minimal; the monitoring, ultrasound
investigations, MRI and follow up are already standard care on our unit. The
blood sample on time point 6 and 64 hours after birth will be collected from an
arterial line (standard care) and the amount of blood is small compared with
the regular volumes of blood samples during the first days in these infants.