Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants: a protocol for the SafeBoosC randomised clinical phase III trial
Language English Country England, Great Britain Media electronic
Document type Clinical Trial Protocol, Journal Article
Grant support
18-3-0133
Elsass Fonden
N/A
Svend Andersen Fonden
PubMed
31888764
PubMed Central
PMC6937938
DOI
10.1186/s13063-019-3955-6
PII: 10.1186/s13063-019-3955-6
Knihovny.cz E-resources
- Keywords
- Near infrared spectroscopy, Preterm, Protocol, Randomised clinical trial,
- MeSH
- Spectroscopy, Near-Infrared * methods MeSH
- Gestational Age MeSH
- Clinical Trials, Phase III as Topic MeSH
- Humans MeSH
- Monitoring, Physiologic * methods MeSH
- Hypoxia, Brain * diagnostic imaging prevention & control MeSH
- Infant, Extremely Premature * MeSH
- Infant, Newborn MeSH
- Oximetry * methods MeSH
- Pragmatic Clinical Trials as Topic MeSH
- Cerebrum * diagnostic imaging MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial Protocol MeSH
BACKGROUND: Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants. METHODS/DESIGN: SafeBoosC III is an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28 weeks postmenstrual age and parental informed consent (unless the site is using 'opt-out' or deferred consent). Exclusion criteria will be no parental informed consent (or if 'opt-out' is used, lack of a record that clinical staff have explained the trial and the 'opt-out' consent process to parents and/or a record of the parents' decision to opt-out in the infant's clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 h after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 h of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36 weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36 weeks postmenstrual age. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants. DISCUSSION: Treatment guided by cerebral NIRS oximetry has the potential to decrease the risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03770741. Registered 10 December 2018.
Copenhagen Trial Unit Rigshospitalet Blegdamsvej 9 2100 Copenhagen Denmark
Department of Cardiology Holbæk Hospital Smedelundsgade 60 4300 Holbæk Denmark
Department of Intensive Care Rigshospitalet Blegdamsvej 9 2100 Copenhagen Denmark
Department of Neonatology Hospices Civil De Lyon 3 Quai des Célestins 69002 Lyon France
Department of Neonatology La Paz University Hospital Paseo De La Castellana 261 28046 Madrid Spain
Department of Neonatology Oslo University Hospital Kirkeveien 166 0450 Oslo Norway
Department of Neonatology Poznan University of Medical Sciences Polna 33 60 535 Poznań Poland
Department of Neonatology Rigshospitalet Blegdamsvej 9 2100 Copenhagen Denmark
Department of Neonatology Royal Hospital for Children 1345 Govan Rd Glasgow G51 4TF UK
Department of Neonatology University Hospital Leuven Herestraat 49 Leuven Belgium
Department of Neonatology University Hospital Motol 5 Uvalu 84 150 06 Prague 5 Czech Republic
Department of Neonatology Wilhelmina Children's Hospital Lundlaan 6 3584 EA Utrecht Netherlands
Department of Pediatrics Medical University of Graz Auenbruggerplatz 30 Graz Austria
NICU Department of Pediatrics University General Hospital of Patras 265 04 Patras Greece
See more in PubMed
Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller A-B, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012;379:2162–2172. doi: 10.1016/S0140-6736(12)60820-4. PubMed DOI
Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010;126:443–456. doi: 10.1542/peds.2009-2959. PubMed DOI PMC
Adams-Chapman I, Heyne RJ, DeMauro SB, Duncan AF, Hintz SR, Pappas A, et al. Neurodevelopmental impairment among extremely preterm infants in the Neonatal Research Network. Pediatrics. 2018;141:e20173091. doi: 10.1542/peds.2017-3091. PubMed DOI PMC
Volpe JJ. Brain injury in the premature infant: neuropathology, clinical aspects and pathogenesis. Semin Pediatr Neurol. 1998;5:135–151. doi: 10.1016/S1071-9091(98)80030-2. PubMed DOI
Ward RM, Beachy JC. Neonatal complications following preterm birth. BJOG An Int J Obstet Gynaecol. 2003;110:8–16. doi: 10.1046/j.1471-0528.2003.00012.x. PubMed DOI
Behrman R, Butler AS. Preterm birth: Causes, consequences and prevention. Institute of Medicine. Washington, D.C.: National Academies Press; 2007. PubMed
Stephens BE, Vohr BR. Neurodevelopmental outcome of the premature infant. Pediatr Clin N Am. 2009;56:631–646. doi: 10.1016/j.pcl.2009.03.005. PubMed DOI
Kluckow M. Low systemic blood flow and pathophysiology of the preterm transitional circulation. Early Hum Dev. 2005;81:429–437. doi: 10.1016/j.earlhumdev.2005.03.006. PubMed DOI
Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–534. doi: 10.1016/S0022-3476(78)80282-0. PubMed DOI
Guzzetta F, Shackelford GD, Volpe S, Perlman JM, Volpe JJ. Periventricular intraparenchymal echodensities in the premature newborn: critical determinant of neurologic outcome. Pediatrics. 1986;78:995–1006. PubMed
Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol. 2009;8:110–124. doi: 10.1016/S1474-4422(08)70294-1. PubMed DOI PMC
Cordeiro CN, Tsimis M, Burd I. Infections and brain development. Obstet Gynecol Surv. 2015;70:644–655. doi: 10.1097/OGX.0000000000000236. PubMed DOI PMC
Prado EL, Dewey KG. Nutrition and brain development in early life. Nutr Rev. 2014;72:267–284. doi: 10.1111/nure.12102. PubMed DOI
Perlman JM. White matter injury in the preterm infant: An important determination of abnormal neurodevelopment outcome. Early Hum Dev. 1998;53:99–120. doi: 10.1016/S0378-3782(98)00037-1. PubMed DOI
Greisen G, Vannucci RC. Is periventricular leucomalacia a result of hypoxic-ischaemic injury? Hypocapnia and the preterm brain. Biol Neonate. 2001;79:194–200. doi: 10.1159/000047090. PubMed DOI
Perlman M, Volpe J. Are venous circulatory abnormalities important in the pathogenesis of hemorrhagic and/or ischemic cerebral injury? Pediatrics. 1987;80:705–711. PubMed
Alderliesten T, Dix L, Baerts W, Caicedo A, van Huffel S, Naulaers G, et al. Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates. Pediatr Res. 2016;79:55–64. doi: 10.1038/pr.2015.186. PubMed DOI
Hyttel-Sorensen S, Austin T, van Bel F, Benders M, Claris O, Dempsey E, et al. 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 tria. Trials. 2013;14:120. doi: 10.1186/1745-6215-14-120. PubMed DOI PMC
Riera J, Hyttel-Sorensen S, Bravo MC, Cabañas F, López-Ortego P, Sanchez L, et al. The SafeBoosC phase II clinical trial: an analysis of the interventions related with the oximeter readings. Arch Dis Child Fetal Neonatal Ed. 2016;101:F333–F338. doi: 10.1136/archdischild-2015-308829. PubMed DOI PMC
European Medicines Agency, Committee for Human Medicinal Products . Guideline on Good Clinical Practice E6(R2) 2017.
Chan A-W, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586. doi: 10.1136/bmj.e7586. PubMed DOI PMC
Davidson JO, Wassink G, van den Heuij LG, Bennet L, Gunn AJ. Therapeutic hypothermia for neonatal hypoxic–ischemic encephalopathy – where to from here? Front Neurol. 2015;6:198. PubMed PMC
Hansen ML, Pellicer A, Gluud C, Dempsey E, Mintzer J, Hyttel-Sorensen S, et al. Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants. Trials. 2019;20:746. PubMed PMC
Pellicer A, Greisen G, Benders M, Claris O, Dempsey E, Fumagally M, et al. The SafeBoosC phase II randomised clinical trial: A treatment guideline for targeted near-infrared-derived cerebral tissue oxygenation versus standard treatment in extremely preterm infants. Neonatology. 2013;104:171–178. doi: 10.1159/000351346. PubMed DOI
Kleiser S, Ostojic D, Andresen B, Nasseri N, Isler H, Scholkmann F, et al. Comparison of tissue oximeters on a liquid phantom with adjustable optical properties: an extension. Biomed Opt Express. 2018;9:86. doi: 10.1364/BOE.9.000086. PubMed DOI PMC
Vermont Oxford Network . Manual of operations: Part 2 data definitions & infant data forms. 2018.
Hyttel-Sørensen S, Pellicer A, Alderliesten T, Austin T, Van Bel F, Benders M, et al. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ. 2015;350:1–11. doi: 10.1136/bmj.g7635. PubMed DOI PMC
Yelland LN, Sullivan TR, Collins CT, Price DJ, McPhee AJ, Lee KJ. Accounting for twin births in sample size calculations for randomised trials. Paediatr Perinat Epidemiol. 2018;32:380–387. doi: 10.1111/ppe.12471. PubMed DOI
Jakobsen JC, Gluud C, Winkel P, Lange T, Wetterslev J. The thresholds for statistical and clinical significance – a five-step procedure for evaluation of intervention effects in randomised clinical trials. BMC Med Res Methodol. 2014;14:34. doi: 10.1186/1471-2288-14-34. PubMed DOI PMC
Greisen G, van Bel F. Equipoise is necessary for randomising patients to clinical trials. Acta Paediatr Int J Paediatr. 2016;105:1259–1260. doi: 10.1111/apa.13549. PubMed DOI
Hyttel-Sørensen S, Greisen G, Als-Nielsen B, Gluud C. Cerebral near-infrared spectroscopy monitoring for prevention of brain injury in very preterm infants. Cochrane Database Syst Rev. 2017;9:CD011506. PubMed PMC
Hunter CL, Oei JL, Suzuki K, Lui K, Schindler T. Patterns of use of near-infrared spectroscopy in neonatal intensive care units: international usage survey. Acta Paediatr. 2018;107:1198–1204. doi: 10.1111/apa.14271. PubMed DOI
Bevan PJW. Should cerebral near-infrared spectroscopy be standard of care in adult cardiac surgery? Hear Lung Circ. 2015;24:544–550. doi: 10.1016/j.hlc.2015.01.011. PubMed DOI
Savović J, Turner RM, Mawdsley D, Jones HE, Beynon R, Higgins JPT, et al. Association between risk-of-bias assessments and results of randomized trials in Cochrane reviews: The ROBES Meta-Epidemiologic Study. Am J Epidemiol. 2018;187:1113–1122. doi: 10.1093/aje/kwx344. PubMed DOI PMC
Hrobjartsson A, Thomsen ASS, Emanuelsson F, Tendal B, Hilden J, Boutron I, et al. Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors. Can Med Assoc J. 2013;185:E201–E211. doi: 10.1503/cmaj.120744. PubMed DOI PMC
Hróbjartsson A, Thomsen ASS, Emanuelsson F, Tendal B, Rasmussen JV, Hilden J, et al. Observer bias in randomized clinical trials with time-to-event outcomes: systematic review of trials with both blinded and non-blinded outcome assessors. Int J Epidemiol. 2014;43:937–948. doi: 10.1093/ije/dyt270. PubMed DOI
Hróbjartsson A, Emanuelsson F, Skou Thomsen AS, Hilden J, Brorson S. Bias due to lack of patient blinding in clinical trials. A systematic review of trials randomizing patients to blind and nonblind sub-studies. Int J Epidemiol. 2014;43:1272–1283. doi: 10.1093/ije/dyu115. PubMed DOI PMC
Anthon CT, Granholm A, Perner A, Laake JH, Møller MH. No firm evidence that lack of blinding affects estimates of mortality in randomized clinical trials of intensive care interventions: a systematic review and meta-analysis. J Clin Epidemiol. 2018;100:71–81. doi: 10.1016/j.jclinepi.2018.04.016. PubMed DOI
Hintz SR, Slovis T, Bulas D, Van Meurs KP. Interobserver reliability and accuracy of cranial ultrasound interpretation in premature infants. J Pediatr. 2007;150:592–596. doi: 10.1016/j.jpeds.2007.02.012. PubMed DOI PMC
Campbell M. Framework for design and evaluation of complex interventions to improve health. BMJ. 2000;321:694–696. doi: 10.1136/bmj.321.7262.694. PubMed DOI PMC
Zwarenstein M, Treweek S, Gagnier JJ, Altman DG, Tunis S, Haynes B, et al. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ. 2008;337:a2390. doi: 10.1136/bmj.a2390. PubMed DOI PMC
Boutron I, Altman DG, Moher D, Schulz KF, Ravaud P. CONSORT statement for randomized trials of nonpharmacologic treatments: A 2017 update and a CONSORT extension for nonpharmacologic trial abstracts. Ann Intern Med. 2017;167:40. doi: 10.7326/M17-0046. PubMed DOI
Brierley J, Larcher V. Emergency research in children: options for ethical recruitment. J Med Ethics. 2011;37:429–432. doi: 10.1136/jme.2010.040667. PubMed DOI
Beauchamp TL, Childress JF, Press. OU . Principles of biomedical ethics. 7. Oxford: Oxford University Press; 2012.
Mason SA, Allmark PJ. Obtaining informed consent to neonatal randomised controlled trials: interviews with parents and clinicians in the Euricon study. Lancet. 2000;356:2045–2051. doi: 10.1016/S0140-6736(00)03401-2. PubMed DOI
Gale C, Juszczak E. A paediatrician’s guide to clinical trials units. Arch Dis Child Educ Pract Ed. 2016;101:265–267. doi: 10.1136/archdischild-2015-310036. PubMed DOI PMC
Gale C, Hyde MJ, Modi N. Research ethics committee decision-making in relation to an efficient neonatal trial. Arch Dis Child Fetal Neonatal Ed. 2017;102:F291–F298. doi: 10.1136/archdischild-2016-310935. PubMed DOI PMC
Hafström M, Källén K, Serenius F, Maršál K, Rehn E, Drake H, et al. Cerebral palsy in extremely preterm infants. Pediatrics. 2018;141:e20171433. doi: 10.1542/peds.2017-1433. PubMed DOI
Roberts G, Anderson PJ, De Luca C, Doyle LW. Changes in neurodevelopmental outcome at age eight in geographic cohorts of children born at 22-27 weeks’ gestational age during the 1990s. Arch Dis Child Fetal Neonatal Ed. 2010;95:F90–F94. doi: 10.1136/adc.2009.165480. PubMed DOI
Stanley F, Blair E, Alberman E. Cerebral palsies: epidemiology and casual pathways. Cambridge: Cambridge University Press; 2000.
Machine Learning Detects Intraventricular Haemorrhage in Extremely Preterm Infants
Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants
Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown
ClinicalTrials.gov
NCT03770741
