title: Computer-determined dosage of insulin in the management of neonatal hyperglycaemia (HINT2): protocol of a randomised controlled trial.
abstract: Neonatal hyperglycaemia is frequently treated with insulin, which may increase the risk of hypoglycaemia. Computer-determined dosage of insulin (CDD) with the STAR-GRYPHON program uses a computer model to predict an effective dose of insulin to treat hyperglycaemia while minimising the risk of hypoglycaemia. However, CDD models can require more frequent blood glucose testing than common clinical protocols. The aim of this trial is to determine if CDD using STAR-GRYPHON reduces hypoglycaemia in hyperglycaemic preterm babies treated with insulin independent of the frequency of blood glucose testing.
  
  
  
  Design: Multicentre, non-blinded, randomised controlled trial.
  
  
  
  Neonatal intensive care units in New Zealand and Australia.
  
  
  
  138 preterm babies ≤30 weeks' gestation or ≤1500 g at birth who develop hyperglycaemia (two consecutive blood glucose concentrations ≥10 mmol/L, at least 4 hours apart) will be randomised to one of three groups: (1) CDD using the STAR-GRYPHON model-based decision support system: insulin dose and frequency of blood glucose testing advised by STAR-GRYPHON, with a maximum testing interval of 4 hours; (2) bedside titration: insulin dose determined by medical staff, maximum blood glucose testing interval of 4 hours; (3) standard care: insulin dose and frequency of blood glucose testing determined by medical staff. The target range for blood glucose concentrations is 5-8 mmol/L in all groups. A subset of babies will have masked continuous glucose monitoring.
  
  
  
  is the number of babies with one or more episodes of hypoglycaemia (blood glucose concentration <2.6 mmol/L), during treatment with insulin.
  
  
  
  This protocol has been approved by New Zealand's Health and Disability Ethics Committee: 14/STH/26. A data safety monitoring committee has been appointed to oversee the trial. Findings will be disseminated to participants and carers, peer-reviewed journals, guideline developers and the public.
  
  
  
  12614000492651.
authors.affiliation: Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand.
authors.forename: Jane
authors.initials: J
authors.lastname: Alsweiler
authors.affiliation: Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Williamson
authors.affiliation: Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Frank
authors.initials: F
authors.lastname: Bloomfield
authors.affiliation: Mechanical Engineering Department, University of Canterbury, Christchurch, New Zealand.
authors.forename: Geoffrey
authors.identifier: 0000-0001-9989-4849
authors.initials: G
authors.lastname: Chase
authors.affiliation: Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Jane
authors.identifier: 0000-0003-2697-1422
authors.initials: J
authors.lastname: Harding
mesh_terms: D003658:Decision Making, Computer-Assisted; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007003:Hypoglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases; D007328:Insulin / Q000627:therapeutic use*; D012107:Research Design
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Biological model; Blood glucose; Clinical decision support system; Hypoglycaemia; Preterm Infant