Reducing bilirubin-induced neurological dysfunction in preterm infants: additional use of the Bilirubin:Albumin Ratio in the treatment of hyperbilirubinemia

ISRCTN	ISRCTN74465643
DOI	https://doi.org/10.1186/ISRCTN74465643
Secondary identifying numbers	NTR935

Submission date: 11/04/2007
Registration date: 11/04/2007
Last edited: 12/04/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Ms Deirdre van Imhoff
Scientific

Beatrix Children's Hospital
University Medical Centre Groningen
Hanzeplein 1
P.O. Box 30001
Groningen
9700 RB
Netherlands

Phone	+31 (0)50 361 4215
Email	d.e.van.imhoff@bkk.umcg.nl

Study information

Study design	Randomised active-controlled parallel-group single-blinded multicentre trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Reducing bilirubin-induced neurological dysfunction in preterm infants: additional use of the Bilirubin:Albumin Ratio in the treatment of hyperbilirubinemia
Study acronym	BARTrial
Study objectives	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(s)	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).
Health condition(s) or problem(s) studied	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
Primary outcome measure	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 study start date	01/04/2007
Completion date	01/04/2010

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	Both
Target number of participants	614
Key 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
Key exclusion criteria	Major congenital malformations, clinical syndromes and chromosomal abnormalities that affect neurodevelopmental outcome
Date of first enrolment	01/04/2007
Date of final enrolment	01/04/2010

Locations

Countries of recruitment

Netherlands

Study participating centre

Beatrix Children's Hospital

Groningen
9700 RB
Netherlands

Sponsor information

University Medical Centre Groningen (UMCG) (The Netherlands)
Hospital/treatment centre

Beatrix Children's Hospital
P.O. Box 30001
Groningen
9700 RB
Netherlands

Website	http://www.umcg.nl/azg/nl/english/azg/
"ROR"	https://ror.org/03cv38k47

Funders

Funder type

Research organisation

The Netherlands Organisation for Health Research and Development (ZonMw) (The Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2008		Yes	No
Results article	results	13/06/2014		Yes	No
Results article	hearing loss results	07/05/2013	12/04/2021	Yes	No

Editorial Notes

12/04/2021: Publication reference added.