Plain English Summary
Not provided at time of registration
Trial website
Contact information
Type
Scientific
Primary contact
Ms Deirdre van Imhoff
ORCID ID
Contact details
Beatrix Children's Hospital
University Medical Centre Groningen
Hanzeplein 1
P.O. Box 30001
Groningen
9700 RB
Netherlands
+31 (0)50 361 4215
d.e.van.imhoff@bkk.umcg.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR935
Study information
Scientific title
Acronym
BARTrial
Study hypothesis
Neonatal jaundice due to unconjugated hyperbilirubinemia occurs in almost all preterm infants and is potentially neurotoxic. The current treatment modalities (phototherapy and exchange transfusion) are based on Total Serum Bilirubin (TSB) levels, but are not evidence based.
TSB is an unreliable predictor of Bilirubin Induced Neurological Dysfunction (BIND). Because low albumin levels appear to potentiate BIND, the Bilirubin:Albumin (B:A) ratio is an interesting additional factor to assess in the management of preterm infants with hyperbilirubinemia.
Ethics approval
The Medical Ethics Review Committee (METC) of the University Medical Center Groningen (UMCG) reviewed and approved the study protocol on the 9th January 2007 (ref: ABR nr: NL 14811.042.06).
Study design
Randomised active-controlled parallel-group single-blinded multicentre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Hyperbilirubinemia, bilirubin induced neurological dysfunction
Intervention
Study group:
Hyperbilirubinemia is evaluated daily, in the first ten days of life using the B:A ratio together with TSB. Treatment guidelines (phototherapy and exchange transfusion limits) are based on B:A ratio and TSB (whichever comes first)
Control group:
Hyperbilirubinemia is evaluated daily, in the first ten days of life using TSB only (care as usual) versus only TSB. Treatment guidelines (phototherapy and exchange transfusion limits) are based on TSB only.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
Blinded assessment of the participants outcome is performed.
Primary outcome:
1. Neurodevelopmental outcome at the age of 18 to 24 months using standardised neurological examination will be measured from October 2008 till April 2010
2. Mental- and Psychomotor Developmental Index scores (MDI and PDI: Dutch version of Bayley scales of infant development II) will be measured from October 2008 till April 2010
Secondary outcome measures
Secondary outcomes:
1. Peak total serum bilirubin will be measured from April 2007 till January 2008
2. Duration of hyperbilirubinaemia will be measured from April 2007 till January 2008
3. Duration of phototherapy will be measured from April 2007 till January 2008
4. Number of exchange transfusions will be measured from April 2007 till January 2008
Other outcomes are complications of prematurity such as:
1. Mortality will be measured from April 2007 till the end of this study (April 2010)
2. Bronchopulmonary Dysplasia (BPD) will be measured from April 2007 till January 2008
3. Patent Ductus Arteriosus (PDA) will be measured from April 2007 till January 2008
4. Retinopathy of Prematurity (ROP) will be measured from April 2007 till January 2008
5. Necrotising Enterocolitis (NEC) will be measured from April 2007 till January 2008
6. Intraventricular Haemorrhage (IVH) etc., will be measured from April 2007 till January 2008
Other potential outcomes to be evaluated in parts of the study population are:
1. Maturation pattern of serial Auditory Brainstem Responses (ABR) in a part of the study populations that is treated in those Neonatal Intensive Care Units (NICUs) that are able to perform serial ABRs. This will be measured from April 2007 till January 2008
2. Free (unbound) unconjugated bilirubin will be measured in from January 2008 till October 2008
3. Lumirubin will be measured from April 2007 till January 2008
4. CFM (Cerebral Function Monitor) will be measured from April 2007 till January 2008
5. Movement score will be measured from April 2007 till January 2008
6. Transcutane bilirubin measurement will be measured from April 2007 till January 2008
Overall trial start date
01/04/2007
Overall trial end date
01/04/2010
Reason abandoned
Eligibility
Participant inclusion criteria
1. Preterm infants born at gestational age less than 32 weeks, either sex
2. Admittance in the first 24 hours of life to a neonatal intensive care unit care centre in the Netherlands
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
614
Participant exclusion criteria
Major congenital malformations, clinical syndromes and chromosomal abnormalities that affect neurodevelopmental outcome
Recruitment start date
01/04/2007
Recruitment end date
01/04/2010
Locations
Countries of recruitment
Netherlands
Trial participating centre
Beatrix Children's Hospital
Groningen
9700 RB
Netherlands
Sponsor information
Organisation
University Medical Centre Groningen (UMCG) (The Netherlands)
Sponsor details
Beatrix Children's Hospital
P.O. Box 30001
Groningen
9700 RB
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
The Netherlands Organisation for Health Research and Development (ZonMw) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
Meeting abstracts:
1. van Imhoff, DE; Dijk, PH; Bos, AF, et al. (2007) Dutch thresholds for unconjugated hyperbilirubinemia in preterm infants: when should treatment be started? ACTA PAEDIATRICA 96: 197-197
2. V W van den Belt, M van der Heide, D E van Imhoff, A F Bos, P H Dijk, C V Hulzebos, and Bart Studygroup (2008) IRRADIANCE LEVELS OF PHOTOTHERAPY IN JAUNDICED PRETERM INFANTS. Arch. Dis. Child. 93: p252
2008 results in: http://www.ncbi.nlm.nih.gov/pubmed/18450807
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24927259
Publication citations
-
Results
Hulzebos CV, van Imhoff DE, Bos AF, Ahlfors CE, Verkade HJ, Dijk PH, Usefulness of the bilirubin/albumin ratio for predicting bilirubin-induced neurotoxicity in premature infants., Arch. Dis. Child. Fetal Neonatal Ed., 2008, 93, 5, F384-8, doi: 10.1136/adc.2007.134056.
-
Results
Hulzebos CV, Dijk PH, van Imhoff DE, Bos AF, Lopriore E, Offringa M, Ruiter SA, van Braeckel KN, Krabbe PF, Quik EH, van Toledo-Eppinga L, Nuytemans DH, van Wassenaer-Leemhuis AG, Benders MJ, Korbeeck-van Hof KK, van Lingen RA, Groot Jebbink LJ, Liem D, Mansvelt P, Buijs J, Govaert P, van Vliet I, Mulder TL, Wolfs C, Fetter WP, Laarman C, , The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial., PLoS ONE, 2014, 9, 6, e99466, doi: 10.1371/journal.pone.0099466.