A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe)

A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4–8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth.Current Controlled Trials ISRCTN78428828. EUDRACT Number 2004-002170-34Perinatal survival in very low birth weight infants (less than 1.5 kg) has increased markedly over the last twenty years with improvements in neonatal intensive care [1]. However mortality rates are as high as 20% in those born less than 1 kg, death may be related to either infection or necrotising enterocolitis. Reducing mortality is an important goal of therapy but it is essential that this be achieved without increasing long term morbidity. Post-natal growth may be sub-optimal particularly with regard to head circumference [2] and this can be associated with neuro-psychological problems particularly in the very low birth weight infant [3], and retinopathy of prematurity is still a major problem [4].Studies of adult intensive care patients have highlighted the importance of blood glucose control on rates of sepsis and survival [5]. In the study reported by Van den Berg, where insulin was used to tightly control blood glucose a reduction in intensive care mortality of 32% (p < 0.04), a reduction in mean ICU stay by 22% (p = 0.005) and a halving of the incidence of bacteraemia (p = 0.00