Plain English Summary
Background and study aims
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, the aim of this study is to compare conventional versus strict control of blood sugar in babies and children undergoing intensive care.
Who can participate?
Children from birth to 16 years of age who are undergoing intensive care treatment.
What does the study involve?
Participants are randomly allocated to receive either conventional care or the new strict blood sugar control treatment (insulin). 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.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Royal Brompton Hospital (UK)
When is the study starting and how long is it expected to run for?
February 2007 to April 2011
Who is funding the study?
Health Technology Assessment Programme (UK)
Who is the main contact?
Dr Duncan Macrae
d.macrae@rbht.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Duncan Macrae
ORCID ID
Contact details
Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom
-
d.macrae@rbht.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HTA 05/506/03; 2006PC008B
Study information
Scientific title
Control of Hyperglycaemia In Paediatric intensive care
Acronym
CHIP
Study hypothesis
Main hypothesis:
For children aged from birth to 16 years on ventilatory support, tight glucose control (TGC) will increase the numbers of days alive and free of mechanical ventilation at 30 days.
Secondary hypotheses:
That TGC will lead to improvement in a range of non-fatal complications associated with intensive care treatment and be cost effective.
More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/0550603
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0018/51228/PRO-05-506-03.pdf
Ethics approval
Brighton East REC, 01/06/2007, ref: 07/Q1907/24
Study design
Randomised controlled interventional trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
http://chip.lshtm.ac.uk/information.html
Condition
Hyperglycaemia
Intervention
Group 1 - Standard treatment
Children in this group will be treated according to a standard, current, approach to blood glucose (BG) management. Insulin will be given by intravenous infusion in this group only if BG levels exceed 12mmol/l on two blood samples taken at least 30 minutes apart and will be discontinued once BG falls to =< 10 mmol/l.
Group 2 - Tight Glycaemic Control
Children in this group will receive insulin by intravenous infusion titrated to maintain a BG between the limits of 4 and 7.0 mmol/l.
Intervention type
Drug
Phase
Not Applicable
Drug names
Insulin
Primary outcome measure
The number of days alive and free from mechanical ventilation within the 30 days after trial entry. Death is obviously an important outcome. Mechanical ventilation can be seen as a measure of disease severity, defining the need for complex intensive care. The concept of ventilator free days (Vedas) brings together these two outcomes. Schoenfeld et al define ventilator free days (VFDs) as: VFD=0 if the child dies before 30 days; VDF=(30-x) if the child is successfully weaned from ventilator within 30 days (where x is the no. of days on ventilator); or VFD=0 if the child is ventilated for 30 days or more. The use of organ failure free days to determine patient-related morbidity surrogate end-points in paediatric trials has been supported by influential paediatric trialists in the current low mortality paediatric critical care environment.
Secondary outcome measures
1. Death within 30 days after trial entry (or before discharge from hospital if duration is greater than 30 days)
2. Death within 12 months of trial entry
3. Number of days in ICU
4. Duration of mechanical ventilation
5. Duration of vasoactive drug usage (adrenaline, noradrenaline, dopamine, dobutamine, or phosphodiesterase type III [PDE-III] inhibitors or vasopressors)
6. Need for renal replacement therapy
7. Blood stream infection (positive cultures associated with two or more features of systemic inflammation or any positive blood culture for fungus)
8. Use of antibiotics >10 days
9. Number of red cell transfusions
10. Number of hypoglycaemic episodes moderate (less than 2.5 mmol/L), severe (less than 2.0 mmol/L)
11. Occurrence of seizures (clinical seizures requiring anticonvulsant therapy)
12. Organ dysfunction score (Pediatric Logistic Organ Dysfunction [PELOD])
13. Hospital length of stay
14. Number of children readmitted within 30 days of trial entry
15. Cost and cost-effectiveness measures:
15.1. Hospital costs within 30 days of trial entry
15.2. Cost per life year (based on 30 days costs and survival)
15.3. Hospital and community health service costs within 12 months of trial entry
15.4. Cost per life year (based on 12 month costs and survival for all cases)
15.5. Cost per disability-free survivor (based on 12 month cost and outcome data for sub group with brain injury)
Overall trial start date
01/02/2007
Overall trial end date
30/04/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Children from birth to 16 years who are undergoing intensive care treatment with an arterial line in-situ and receiving both mechanical ventilation and vasoactive support drugs following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours.
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
1,500
Participant exclusion criteria
1. Children born pre-term and who are < 36 weeks corrected gestation
2. Children with diabetes mellitus
3. Children with an established or suspected diagnosis of an inborn error of metabolism
4. Children for whom treatment withdrawal or limitation of intensive care treatment is being considered
5. Children who have been in a PICU for more than 5 days in succession
6. Children admitted to a PICU who have already participated in the CHIP study during a previous PICU admission
Recruitment start date
01/02/2007
Recruitment end date
30/04/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Brompton Hospital
London
SW3 6NP
United Kingdom
Sponsor information
Organisation
Royal Brompton & Harefiled NHS Trust (UK)
Sponsor details
Sydney Street
London
SW3 6NP
United Kingdom
-
m.cross@rbht.nhs.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2010 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/20137090
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24401049
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24780450
Publication citations
-
Protocol
Macrae D, Pappachan J, Grieve R, Parslow R, Nadel S, Schindler M, Baines P, Fortune PM, Slavik Z, Goldman A, Truesdale A, Betts H, Allen E, Snowdon C, Percy D, Broadhead M, Quick T, Peters M, Morris K, Tasker R, Elbourne D, Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol., BMC Pediatr, 2010, 10, 5, doi: 10.1186/1471-2431-10-5.
-
Results
Macrae D, Grieve R, Allen E, Sadique Z, Morris K, Pappachan J, Parslow R, Tasker RC, Elbourne D, , A randomized trial of hyperglycemic control in pediatric intensive care., N. Engl. J. Med., 2014, 370, 2, 107-118, doi: 10.1056/NEJMoa1302564.
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Results
Macrae D, Grieve R, Allen E, Sadique Z, Betts H, Morris K, Pappachan VJ, Parslow R, Tasker RC, Baines P, Broadhead M, Duthie ML, Fortune PM, Inwald D, McMaster P, Peters MJ, Schindler M, Guerriero C, Piercy D, Slavik Z, Snowdon C, Van Dyck L, Elbourne D, A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial., Health Technol Assess, 2014, 18, 26, 1-210, doi: 10.3310/hta18260.