Safeguarding the brain of our smallest children – a phase III randomised clinical trial on near-infrared spectroscopy monitoring combined with a treatment guideline in premature infants with clinically relevant outcomes

The aim is to conduct a large, pragmatic trial in extremely preterm babies to examine if cerebral oximetry combined with the treatment guideline can reduce the risk of death or severe brain injury at 36 weeks of age from 34% in the control group to 26% in the experimental group.

SafeBoosC-III will use any oximeter that is approved for clinical use that has been calibrated in the blood-lipid phantom to define the hypoxic threshold for clinical action. This makes it a trial of the generic principle of tissue oximetry-guided therapy.

In 2015 we formed a group of 93 neonatal units in 17 European countries and applied to the Horizon2020 research programme

In 2016 we formed a consortium with 10 national partners and applied to the Irish Heath Research Board in 2016 - we were not funded.
We then considered a cluster randomized design. The SafeBoosC intervention is complex: Monitoring of cerebral oxygenation as well as implementation of the treatment guideline 24/7. This means that many clinical staff members are involved and therefore a cluster design would be appropriate. But such a design would require the participation of approximately 140 NICUs. 
In 2017 we applied to the NovoNordicFoundation for a trial planning to involve 50 NICUs to enroll 1600 infants in a pragmatic, individually randomized clinical trial over a period of two years. This was not granted.
In April 2018 the initial trial center costs for a trial with this design were funded by ElsassFonden. Twenty national coordinators were identified and 125 NICUs from Europe, China and the US showed interest and in November we hosted investigators from 70 hospitals at hotel BellaSky in Copenhagen. 

In 2018 we also applied to the Medtronics Foundation, to cover local GCP expenses and insurance. This was not granted.  On the other hand, the industries EnginMed and OxyPrem contribute and many hospitals have obtained funding to cover local costs.
In 2019 we were granted 1,000,000 dkk from Svend Andersen Foundation and Aage and Johanne Louis-Hansen Foundation, respectively. This funding will cover expenses to Copenhagen Trial Unit, three additional investigator meetings and one year extra salary to the trial manager. 

In 2019 the protocol and statistical analysis plan was published in Trials Journal. We also opened the web-based systems for training and certification and randomised the first baby early summer 2019. 

In 2020 January, we held the second investigator meeting at Bella Sky in Copehagen with investigators from 60 hospitals participating. In February 2020, 26 hospitals have started randomising and more than 125 babies have been included. Furthermore, an additional 33 hospitals have ethics approval and are preparing for participation as well.

All materials are available at this website in public space.