Details of HTA project in progress
Last updated: 1 February 2012 - Next update due: 8 February 2012
Research type: |
Primary Research (e.g. trial) |
Project title: |
Control of Hyperglycaemia in Paediatric intensive care trial (the CHIP trial) |
Project ref: |
05/506/03 |
Cost: |
£1,609,887 |
Chief Investigator : |
Dr Duncan Macrae, Director, Paediatric Intensive Care Unit, Royal Brompton Hospital |
Start Date: |
February 2007 |
Estimated date of publication in HTA journal series: |
Mid 2013. This date takes account of time for report preparation and printing based on current average times for these activities. |
Plain English Summary |
When children are severely ill or recovering from major surgery they often require treatment in specialist children's intensive care units. It is frequently observed that under such circumstances, children's blood sugar levels rise. Traditionally this has been dismissed as unimportant. Recently research in the laboratory and adults has questioned this view. A large study randomly assigned adults in intensive care to conventional treatment (allowing blood sugar to rise) or to receive a drug, insulin, which was used to maintain blood sugar levels strictly within normal limits. There were 43% fewer deaths and similar reductions in serious complications in the adults receiving the insulin treatment. Babies and children are not small adults, and it cannot be assumed that the benefits seen in adults will occur in children. As we do not know whether the new blood sugar management will help children, we plan to conduct a clinical trial comparing conventional versus strict control of blood sugar in babies and children undergoing intensive care. This will be undertaken in specialist children's intensive care units across the UK. Parents or guardians will be approached, given information about the study and asked if they agree to their child's participation. For planned surgery, older children may also be asked directly. It is planned to allocate half of the children to conventional care and half of the children to the new 'strict blood sugar control' treatment. We hope to find out whether strict control of blood sugar by using insulin leads to fewer deaths, fewer complications and faster recovery of children in intensive care. To do this we have calculated we need to recruit 1500 children over a period of 2 years. We believe the risks of the research to the child will be minimal. The researchers are from the major paediatric intensive care units in the UK and the London School of Hygiene and Tropical Medicine. They have wide experience of conducting clinical trials in neonatal and paediatric intensive care, and of using insulin to control blood sugar. Parents whose children have experienced intensive care are represented on the trial Steering Committee. Claire Snowdon, a member of the Steering Committee, has conducted research on the experiences of parents whose children have been involved in similar research projects. Part of the cost of the support requested relates to research nurses. We believe their role to be central to ensuring effective communication with parents during recruitment, and ensuring high standards of training about the intervention to staff in regional PICUs. |
Project Abstract: |
Design: Primary Research: Pragmatic randomised controlled clinical trial. Setting: 10 Regional Paediatric Intensive Care Units in the UK Target population: Children aged to 16 years undergoing intensive care treatment who are receiving mechanical ventilation and inotropic support drugs and in whom it is anticipated that such treatment will continue for at least 12 hours. Children born preterm (< 36 weeks gestation), those with diabetes mellitus (Type 1) or for whom treatment withdrawal or limitation of intensive care treatment is being considered will be excluded. Health technology being assessed: Elevated blood glucose levels frequently occur following injury, major surgery or in association with major illness in children. Conventional management is to intervene to lower glucose levels with an intravenous infusion of insulin only if the glucose level exceeds approximately 12 mmol/l (Personal communication, K. Morris, UK Survey, 2006). An alternative strategy, tight glycaemic control using insulin to maintain blood glucose strictly within normal limits of 5-7 mmol/l may improve outcomes in critically ill and stressed children, as it has been shown to do in adult patients. It is not possible to blind the administration of insulin, as its impact on blood glucose levels must be closely monitored and adjustments made. Measurement of costs and outcomes: Following the influential ARDSNET study (NEJM 2000: 342;1301) we will use as the primary outcome the number of days alive and free from mechanical ventilation (VFDs) 30 days after trial entry. Death is an important outcome and is unlikely to be influenced by investigator bias. The clinical investigators consider that mechanical ventilation 'defines' need for complex intensive care and that its discontinuation will be the result of application of standard clinical care protocols rather than trial-driven bias. Secondary measurement of outcomes are: death in hospital, no. days in ICU; no. patients >4 days in ICU ; duration of mechanical ventilation; duration of inotropic drug usage; renal impairment (creatinine > 100 mol/l; need for renal replacement therapy; blood stream infection; use of antibiotics >10 days; hypoglycaemic episodes; seizures; and a measure of multi-organ dysfunction using PELOD. A full cost and cost-effectiveness analysis will be undertaken to assess whether the costs of achieving tight blood glucose control are justified by subsequent reductions in hospitalisation costs and/or by improvements in patient outcomes. Information will be collected on the resources required under both policies. Unit costs for hospital services and community care costs will be taken from appropriate reference costs databases, with some more detailed unit costs if required. Total costs will be estimated by valuing each resource use item by the appropriate unit cost. The analysis will also combine the clinical and cost data in a cost-effectiveness analysis, and report cost per death averted and cost per adverse event averted. Sensitivity analysis will be conducted to test how robust the conclusions are to assumptions made in the analysis. Based on information from PICANet, the target sample size is 1500 patients. This has over 90% power to detect an effect size of 2 VFDs within the first 30 days post-randomisation. This size not only allows for random error in the estimate of the standard deviation (assumed as 7 VFds), and for non-compliance (some patients allocated to tight control not receiving this, and some allocated to usual care being managed with tight control), but also crucially has 80% power to test for interaction between the effect of the tight glucose control and key prognostic factors (such as whether the child is a cardiac or non-cardiac patient). |
NRR* number, if applicable: |
N0484190624 (*National Research Register). The National Research Register was a public database of ongoing and recently completed research projects funded by, or of interest to, the United Kingdom's National Health Service (NHS). It is now an archive of projects from early 2000 to September 2007. Search the NRR archive. |
ISRCTN* number: | ISRCTN 61735247 (*International Standard Randomised Controlled Trial Number) URL of this project on the Controlled Trials Website: http://www.controlled-trials.com/ISRCTN61735247 |
Project Protocol: |
Project protocol (pdf format, 256 kbytes) |
URL of this page: |
http://www.hta.ac.uk/1533 |
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