None listed
Conditions
Brief summary
High blood sugar levels are common in patients who are critically ill even if they do not have a history of diabetes. Glucagon-like-peptide-1 (GLP-1) is thought to be an alternative treatment to control high blood sugar levels in intensive care patients as it has the advantage of not causing low blood sugar levels. The purpose of this study is to compare glycaemic control between exogenous intravenous glucagon-like peptide-1 (GLP-1) and insulin for the management of stress-induced hyperglycaemia in critically ill patients. The study is a randomised, double-blind, double-dummy, parallel study comparing GLP-1 and insulin intravenous infusions over 48 hours in critically ill patients. It is hypothesised that there will be no difference in the time outside target glucose range (4.0 – 10.0 mmol/L) between exogenous intravenous GLP-1 and insulin infusions.
Interventions
The CONTROL study aims to compare glycaemic control between exogenous intravenous glucagon-like peptide-1 (GLP-1) and insulin infusions for the management of stress-induced hyperglycaemia in critically ill patients.
A total of 40 sedated and mechanically ventilated critically ill patients with stress hyperglycaemia will be recruited from the Intensive Care Unit at the Royal Adelaide Hospital (RAH). Participants will be randomised and blinded to the intervention or control arm and commenced on e
The CONTROL study aims to compare glycaemic control between exogenous intravenous glucagon-like peptide-1 (GLP-1) and insulin infusions for the management of stress-induced hyperglycaemia in critically ill patients. A total of 40 sedated and mechanically ventilated critically ill patients with stress hyperglycaemia will be recruited from the Intensive Care Unit at the Royal Adelaide Hospital (RAH). Participants will be randomised and blinded to the intervention or control arm and commenced on either therapy over a 48-hour period. GLP-1 and Placebo: - Synthetic GLP-1 will be reconstituted by the Royal Adelaide Hospital Department of Pharmacy as a solution in 4% albumin and presented in an opaque syringe for intravenous infusion. - The placebo will be 4% albumin presented in an opaque syringe and indistinguishable from the active drug (GLP-1). Insulin and Placebo: - Insulin will be diluted by pharmacy with 0.9% saline to 1 Unit per mL and presented in an opaque syringe for intravenous infusion. This is the standard of care insulin brand and concentration used in the RAH ICU. - Placebo will be 0.9% saline presented in an opaque syringe and indistinguishable from the active drug (insulin). Intervention arm: Intravenous GLP-1 at an initial dose of 1.2 pmol/kg/min (10 mL/hr). ‘Placebo insulin’ (0.9% saline) titrated accordingly. Following consent, a subcutaneous continuous glucose monitor (CGM) will be placed on the abdomen of the patient. Glucose concentrations will be recorded at 5 minute intervals with results blinded to the bedside clinical staff and study investigators. Blood glucose concentrations will also be measured hourly using a portable glucose meter and eight hourly using arterial blood gas measurements (as per standard care). 4 hours before study commencement, nasogastric feeds will be held. Prior to the study commencing, the nasogastric tube will be aspirated and the volume recorded and discarded. Glucose absorption will be assessed using 3-O-methyl-D-gluco-pyranose (3-OMG). Nasogastric feeds will be recommenced at T = 0 with a bolus of 3 g of 3-OMG dissolved in 50 mL of enteral formula and then a continuous rate determined by the treating physician. Blood samples of 5 mL will be collected every 30 minutes until T = 360 min (total of 13 samples = 65 mL of blood) and gastric residual volume will be measured 6-hourly by nasogastric aspirates throughout the study period. Blood samples will be analysed for plasma 3-OMG concentration using High Performance Liquid Chromatography (HPLC). The rate of glucose absorption is indicated by the area under the 3-OMG concentration curve, peak 3-OMG concentration and the time to peak concentration. Blood samples will be taken to quantify plasma concentrations of C-peptide, glucagon, GLP-1 and GIP. 3mL blood samples will be taken at study commencement and subsequently at T = 30, 60, 90, 120, 150, 180,210, 240, 270, 300, 330, 360 minutes and at study completion (T = 48 hours). The study will be censored at T = 48 hours and patients returned to usual care.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
All mechanically ventilated critically ill patients admitted to the Royal Adelaide Hospital Intensive Care Unit are eligible if: • Aged equal to or between 18 and 80 years old • Stress hyperglycaemia with a blood glucose of greater than or equal to 11.1 mmol/L • About to commence or commenced intravenous insulin • Expected to be in ICU until the end of the next calendar day
Exclusion criteria
• History of type 1 or type 2 diabetes mellitus • Glycated haemoglobin (HbA1c) is greater than or equal to 6.5% • Contraindication to enteral nutrition • Expected to be eating orally before the end of the next calendar day • Pregnancy (a ßHCG will be performed on all women of child-bearing age) • Haemoglobin is less than 80 g/L • Patients with traumatic brain injury (albumin contraindicated) • Previous surgery on the oesophagus, stomach or small intestine • History of pancreatitis • Death during ICU is deemed inevitable Withdrawal criteria is classified as: • BGL is greater than 12 mmol/L for more than 10 hours despite maximal insulin or GLP-1 therapy. • BGL is greater than 16 mmol/L after 6 hours of study commencement (i.e. T is greater than 6 hours) • BGL is greater than 20 mmol/L at any time point • BGL is less than 2.2 mmol/L at any point. • Two or more episodes of vomiting or overt regurgitation within a 12-hour period. • Next of kin may withdraw consent at any time.
Outcome results
None listed