Neonatal Insulin Replacement Therapy in Europe Study


Study Summary


What is the problem to be addressed?

The common problem of hyperglycaemia (high blood glucose levels) in the very low birth weight baby.



Study Aims

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.



Study Background

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.



Study Design

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.



Intervention

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 neonatal care.



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.


Data Collection

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 at discharge.



Outcome Measures

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).



Follow Up

Each baby is followed until it is discharged from neonatal intensive care. Further follow up will occur at ages 1 and 2 years.



External Committees

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.

Contact Details for Further Information
Clinical Trials Office
University Department of Paediatrics
Box 116, Addenbrooke's Hospital
Hills Road
Cambridge CB2 0QQ
United Kingdom
Tel.: +44 (0)1223 763130
Fax.: +44 (0)1223 336996

Direct email to the Nirture team