Condition category
Nervous System Diseases
Date applied
11/04/2007
Date assigned
11/04/2007
Last edited
16/06/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.neonatologiestudies.nl

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

http://www.umcg.nl/azg/nl/english/azg/

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

  1. 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.

  2. 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.

Additional files

Editorial Notes