KCE-181144: A pragmatic, open label, multinational randomized phase III clinical trial evaluating treatment based on near-infrared spectroscopy monitoring versus treatment as usual in premature infants - SAFEBOOSC III

Summary (French or Dutch)

Each year, 50,000 extremely preterm infants are born in high-income countries with access to neonatal intensive care. Of these, 10,000 will die and a further 10,000 will suffer cerebral disability. Time spent outside normal cerebral oxygenation ranges is associated with poor neurological outcome in children and adults. Monitoring of cerebral oxygenation may reduce the risk of cerebral complications.

The objective of the SafeBoosC-III trial is to investigate the benefit and harms of measuring the level of oxygen in the brain based on near-infrared spectroscopy (NIRS) monitoring to compared with treatment as usual. The hypothesis is that measuring the oxygen level in the brain in extremely preterm infants during the first 72 hours of life may result in a reduction in severe brain injury or death at 36 weeks postmenstrual age.

Eligible infants will be born before 28 weeks of postmenstrual age; with the decision made to provide full life support and cerebral (NIRS) oximeter can be placed within 6 hours after birth.

Participants in the experimental group will be monitored during the first 72 hours of life with a cerebral (NIRS) oximeter. Participants in the control group will not undergo cerebral oxygenation monitoring and will be treated as usual. Each participant will be followed up at 36 weeks postmenstrual age.

Trial Description
Title

An investigator-initiated, pragmatic, open label, multinational randomized phase III clinical trial evaluating treatment based on near-infrared spectroscopy monitoring versus treatment as usual in premature infants

Participants (P)

Eligible infants will be born before 28 weeks of postmenstrual age; decision is made to provide full life support; signed informed consent (unless the NICU has chosen to use ‘opt-out’ or deferred consent as consent method); and cerebral NIRS oximeter placed within 6 hours after birth.

Intervention (I)

Participants in the experimental group will be monitored during the first 72 hours of life with a cerebral NIRS oximeter, placed within six hours after birth, and treated according to an evidence-based treatment guideline.

Control (C)

Participants in the control group will not undergo cerebral oxygenation monitoring and will be treated as usual. Each participant will be followed up at 36 weeks postmenstrual age.

Outcome (O)

The primary outcome will be a composite of severe brain injury (cerebral haemorrhage grade III or IV, cystic periventricular leukomalacia, cerebellar haemorrhage, post-haemorrhagic ventricular dilatation or cerebral atrophy) detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to that age or death until 36 weeks of postmenstrual age.

Trial Design

The SafeBoosC-III trial will be an investigator-initiated, randomized, multinational, pragmatic phase-III clinically open trial with a two-parallel group design. Sixteen-hundred extremely preterm infants will be included within 24 months at 50 neonatal intensive care units (NICUs) across 20 countries (less than two children per month per unit). Data management and statistical analysis will be blinded.

Participating countries: Austria, Denmark, Czech Republic, France, Germany, Greece, Ireland, Italy, The Netherlands, Norway, Poland, Portugal, Spain, Switzerland, Turkey, UK, USA, India, China.

Sample Size

Sample size was calculated based on the primary outcome with an alpha of 5%, a power of 90%, and a ratio of 1:1 between intervention groups. In the SafeBoosC-II trial, the proportion of trial participants in the control group with death or severe brain injury was approximately 34%. Assuming the same proportion in the SafeBoosC phase III trial control group and using 22% relative risk reduction as anticipated intervention effect, we will need to randomise a total of 1,600 participants

Belgian centres are planned to recruit 100 patients

Trial duration

39 months

Budget

€600 000. General project management and data management by the sponsor team in Denmark. Local project management and monitoring by the Belgian Coordinating Centre

Status

Open

 

Trial team

Sponsor

International Sponsor: Rigshospitalet , Copenhagen – Denmark

Belgian Coordinating Center: UZ Leuven

Chief Investigator

 

Prof. Gunnar Naulaers

 

Sites

  1. UZ Leuven
  2. AZ Brugge
  3. TIVOLI ( La Louvière)
  4. CHU Liège
  5. Grand Hôpital de Charleroi
  6.  Clinique St Vincent (Rocourt, Liège)
Documents
Protocol  
Report

Q4/2022

Publication

 

References

Clinicaltrials.gov: pending

Webpage: 

Funding scheme

2018 Investigator led