Insulin Replacement Therapy in Europe Study
What is the problem to be addressed?
The common problem of hyperglycaemia (high blood glucose levels) in the
very low birth weight baby.
The primary aim of the study is to investigate whether an early fixed
dose insulin infusion, combined with variable dextrose (glucose)
support to maintain normoglycaemia (normal blood glucose levels), will
reduce mortality in the very low birth weight baby.
In 2001 van den Berghe and colleagues reported their important
observations of the effects of intensive insulin therapy in critically
ill adult patients in intensive care (New
England Journal of Medicine 2001; 345:1359-1367). In that
study, where insulin was used to tightly control blood glucose levels
they observed a reduction in intensive care mortality of 32 %
(p<0.04), of mean length of intensive care stay of 22 %
(p=0.005) and a halving of the incidence of bacteraemia (the presence
of bacteria in the blood) (p=0.003).
Although the medical conditions encountered in adult intensive care are
not the same as those seen in neonatal units, there are many parallels
and the relationship between hyperglycaemia, morbidity and mortality
has already been suggested by previous studies in very low birth weight
(less than 1500 g) new born infants.
A European multi-centre, randomised controlled trial of the effect of
early continuous insulin replacement, titrated with 20% dextrose to
maintain normoglycaemia for 7 days in the very low birth weight infant,
on the outcomes of mortality, morbidity and cost-effectiveness.
500 babies will be recruited from 10 centres over 2 years.
Babies will be randomised to receive either a continuous infusion of
insulin (0.05 units/kg/hr) from within 24 hours of birth and for the
first 7 days of life, or to act as controls and receive standard
Monitoring of Glucose Control
All babies will have Continuous Glucose Monitors fitted.
What Are The Planned Inclusion Criteria?
1. the baby's birth weight is less than 1500 g.
2. the baby requires intensive care.
3. the baby is less than 24 hours old.
Case Report Forms will be complete on each baby for weeks 1-4, at the
equivalent of 36 weeks of gestation, at expected dates of delivery and
The primary outcome is mortality on or before the expected dates of
delivery. Secondary outcomes include growth, sepsis, number of days in
neonatal intensive care, total costs per patient, incremental cost and
presence of complications related to very low birth weight (necrotising
enterocolitis, retinopathy of prematurity, intracranial haemorrhage,
chronic lung disease).
Each baby is followed until it is discharged from neonatal intensive
care. Further follow up will occur at ages 1 and 2 years.
The Nirture study has two external committees overseeing it, the Trial
Steering Committee (chaired by Professor Kate Costeloe) and the Data
Monitoring Committee (chaired by Professor Mike Preece). Both
committees meet every 6 months.
Details for Further Information
Clinical Trials Office
University Department of Paediatrics
Box 116, Addenbrooke's Hospital
Cambridge CB2 0QQ
Tel.: +44 (0)1223 763130
Fax.: +44 (0)1223 336996
email to the Nirture team