Exenatide for Stress Hyperglycemia (ExSTRESS)
Stress hyperglycemia is a common phenomenon in cardiac surgery that concerns diabetic and non diabetic patients.
It has been shown that perioperative hyperglycemia is an independent risk factor of postoperative mortality and morbidity.
The Leuven et al.'s study suggested that strict glycemic perioperative control using an intensive insulin therapy could reduce mortality and morbidity in surgical intensive care's patients. This study included a majority of cardiac surgery patients. Others studies have suggested that the beneficial effect of insulin-based tight perioperative glycemic control might be hampered by iatrogenic hypoglycemia. Moreover, insulin therapy failed to obtain perioperative glycemic stability in most patients.
Exenatide (Byetta ®) is an incretin mimetic, characterized by an anti-hyperglycemic effect that depends on the blood glucose level.
We hypothesize that continuous intravenous infusion of exenatide could improve perioperative glycemic control and stability and could reduce the risk of iatrogenic hypoglycemia compared to a conventional insulin therapy during the perioperative period of cardiac surgery.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Intravenous Exenatide (Byetta®) Versus Insulin for Perioperative Glycemic Control in Cardiac Surgery: the Open-labeled Randomized Phase II/III ExStress Study|
- Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
The percentage of time spent achieving blood glucose control is defined as the ratio between the total time spent achieving blood glucose control and the total time under treatment.
Blood glucose measurement will be done hourly. Blood glucose control is considered to be achieved between 2 blood glucose measurements if the first blood glucose value measured belongs to blood glucose target interval, defined as blood glucose level between 100 mg/dl l and 140 mg/dl l.
- Hypoglycemia [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]Hypoglycemia is defined as blood glucose level less than 80 mg/dl.
- Severe hypoglycemia [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]Severe hypoglycemia is defined as blood glucose level less than 40 mg/dl.
- Number of patients needing rescue to insulin therapy protocol [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
- Number of adverse events occuring in the exenatide group [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]As the safety of exenatide has never been assessed in the perioperative period in cardiac surgery, all adverse events will be reported, in particular: known adverse events (diarrhea, nausea, vomiting) et severe adverse events (pancreatitis, acute renal failure, death, cardiac arrest).
- Mortality [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
- Postoperative morbidity [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
Postoperative morbidity is defined as:
- neurological complications: stroke.
- renal complication: acute renal failure requiring dialysis.
- cardiac complication: cardiogenic shock, arrhythmia, myocardial infarct.
- vasopressive drug support in postoperative intensive care unit.
- length of postoperative mechanical ventilation.
- infectious complication: deep sternal infection.
- The mean (GluAve) and standard deviation (GluSD) of blood glucose [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
- The coefficient of variability (GluCV) of blood glucose level [ Time Frame: 48 hours ] [ Designated as safety issue: No ]GluCV = GluSD*100/GluAve
- Mean number of blood glucose measured [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
- Mean difference between each blood glucose measurement and 120 mg/dl [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
- Perioperative cardiac mortality [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
- Perioperative non cardiac mortality [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
- Length of stay in intensive care unit [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
|Study Start Date:||January 2015|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Exenatide group
Exenatide. Exenatide: bolus of 0.05 µg/min infused during the 1st hour of treatment, followed by a continuous infusion of 0.025 µg/min until the end of treatment.
The exenatide therapy will begin as soon as a blood glucose level is above 140 mg/dl will be measured. A of exenatide will be intravenously .
The treatment will be administrated during the first postoperative 48 hours in the intensive care unit or until intensive care unit discharge if this event occurs earlier.
Active Comparator: Insulin group
Insulin: Humalog (insulin lispro human analog). The insulin therapy will begin as soon as a blood glucose level is above 140 mg/dl will be measured.
The dose of insulin intravenously infused will be adapted to blood glucose measurements, following the insulin therapy protocol used in our department.
The insulin therapy protocol used in our department and prescribed as the benchmark treatment in the present study has been validated in a previous study. It has been derived from the protocol validated by Goldberg et al.
Other Name: Humalog Insulin Lispro Human Analog
The phase II of the study will assess the safety and the efficacy of a continuous intravenous infusion of exenatide for the management of post operative stress hyperglycemia after planned coronary artery graft bypass (CABG) surgery.
A nested cohort study will concern the 24 first patients included in the study (12 patients/group) to assess the impact of a continuous intravenous infusion of exenatide on post operative glycemic variability after planned CABG surgery.
The aim of the phase III of the study will compare the efficacy of a continuous intravenous infusion of exenatide to the gold standard treatment, i.e the intravenous infusion of short-acting insulin, for the management of post operative stress hyperglycemia after planned CABG surgery.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01969149
|Contact: Guillaume BESCH, MDemail@example.com|
|Post operative intensive care unit of the cardiac surgery department||Recruiting|
|Besançon, France, 25030|
|Contact: Guillaume Besch, MD firstname.lastname@example.org|
|Principal Investigator:||Guillaume Besch, MD||CHRU Besançon|
|Study Director:||Sébastien Pili-Floury, MD, PhD||CHRU Besançon|