Open Access Study protocol

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

Simon Hyttel-Sorensen1*, Topun Austin2, Frank van Bel3, Manon Benders3, Olivier Claris4, Eugene Dempsey5, Monica Fumagalli6, Gorm Greisen1, Berit Grevstad7, Cornelia Hagmann8, Lena Hellström-Westas109, Petra Lemmers3, Jane Lindschou7, Gunnar Naulaers11, Wim van Oeveren12, Adelina Pellicer13, Gerhard Pichler14, Claudia Roll15, Maria Skoog7, Per Winkel7, Martin Wolf16 and Christian Gluud7

Author Affiliations

1 Department of Neonatology, Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark

2 Rosie Maternity Hospital Cambridge University Hospitals NHS Foundation Trust Hills Road, Cambridge, CB2 0SW, UK

3 Wilhelmina Children’s Hospital, Universitair Medisch Centrum Utrecht, KE 04.123.1, PO Box 85090, Utrecht, 3508 AB, The Netherlands

4 Department of Neonatology, Hopital Femme Mere Enfants, 59, Boulevard Pinel, Bron, 69500, France

5 Department of Paediatrics and Child Health, University College Cork, College Road, Cork, Ireland

6 NICU, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan, Via della Commenda 12, Milan, IT- 20122, Italy

7 Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark

8 Division of Neonatology, University of Zurich, Zurich, 8091, Switzerland

9 Department of Women’s and Children’s Health Uppsala Universitet, University Hospital, Uppsala, 751 85, Sweden

10 Department of Neonatology, University Hospital, Uppsala, 751 85, Sweden

11 Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium

12 Haemoscan B.V, Stavangerweg 23, Groningen, JC, 9723, The Netherlands

13 Department of Neonatology, La Paz University Hospital, Paseo de la Castellana 261, Madrid, 28046, Spain

14 Department of Pediatrics, Medical University of Graz, Auenbruggerplatz 30, Graz, Austria

15 Department of Neonatology and Paediatric Intensive Care, Vest Children’s Hospital Datteln, University Witten-Herdecke, Dr.-Friedrich-Steiner-Str. 5, Datteln, 45711, Germany

16 Biomedical Optics Research Laboratory, Division of Neonatology, University Hospital Zurich, Frauenklinikstr 10, Zurich, 8091, Switzerland

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Trials 2013, 14:120  doi:10.1186/1745-6215-14-120

Published: 1 May 2013

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/Design

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.

Discussion

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.

Trial registration

ClinicalTrial.gov, NCT01590316

Keywords:
Randomized clinical trial; Preterm; Near infrared spectroscopy; Protocol