title: A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO2.
  
  
  METHODS
  SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO2 values outside the target ranges of 55% to 85%, that is, the 'burden of hypoxia and hyperoxia' expressed in '%hours'. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events.
  
  
  CONCLUSIONS
  Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia.
  
  
  BACKGROUND
  ClinicalTrial.gov, NCT01590316.
authors.affiliation: Department of Neonatology, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark. simonhyttelsrensen@me.com
authors.forename: Simon
authors.initials: S
authors.lastname: Hyttel-Sorensen
authors.forename: Topun
authors.initials: T
authors.lastname: Austin
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Manon
authors.initials: M
authors.lastname: Benders
authors.forename: Olivier
authors.initials: O
authors.lastname: Claris
authors.forename: Eugene
authors.initials: E
authors.lastname: Dempsey
authors.forename: Monica
authors.initials: M
authors.lastname: Fumagalli
authors.forename: Gorm
authors.initials: G
authors.lastname: Greisen
authors.forename: Berit
authors.initials: B
authors.lastname: Grevstad
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hagmann
authors.forename: Lena
authors.initials: L
authors.lastname: Hellström-Westas
authors.forename: Petra
authors.initials: P
authors.lastname: Lemmers
authors.forename: Jane
authors.initials: J
authors.lastname: Lindschou
authors.forename: Gunnar
authors.initials: G
authors.lastname: Naulaers
authors.forename: Wim
authors.initials: W
authors.lastname: van Oeveren
authors.forename: Adelina
authors.initials: A
authors.lastname: Pellicer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pichler
authors.forename: Claudia
authors.initials: C
authors.lastname: Roll
authors.forename: Maria
authors.initials: M
authors.lastname: Skoog
authors.forename: Per
authors.initials: P
authors.lastname: Winkel
authors.forename: Martin
authors.initials: M
authors.lastname: Wolf
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
mesh_terms: D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000098:blood supply* / Q000254:growth & development / Q000378:metabolism; D002560:Cerebrovascular Circulation; D002657:Child Development; D002985:Clinical Protocols; D004569:Electroencephalography; D005060:Europe; D005865:Gestational Age; D019983:Guideline Adherence; D006801:Humans; D018496:Hyperoxia / Q000209:etiology / Q000517:prevention & control; D000860:Hypoxia / Q000209:etiology / Q000517:prevention & control; D007226:Infant Mortality; D062071:Infant, Extremely Premature / Q000097:blood*; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D015931:Intensive Care, Neonatal / Q000379:methods* / Q000592:standards; D008279:Magnetic Resonance Imaging; D008991:Monitoring, Physiologic / Q000379:methods* / Q000592:standards; D010092:Oximetry / Q000592:standards; D010100:Oxygen / Q000097:blood; D010102:Oxygen Inhalation Therapy / Q000009:adverse effects / Q000592:standards; D017410:Practice Guidelines as Topic; D012107:Research Design; D019265:Spectroscopy, Near-Infrared / Q000592:standards; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010100:Oxygen