ExSTRESS: Exenatide for Stress Hyperglycemia
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: Exenatide
Other Names:
|
| 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. |
Drug: Insulin
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl) [48 hours]
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.
Secondary Outcome Measures
- Hypoglycemia [48 hours]
Hypoglycemia is defined as blood glucose level less than 80 mg/dl.
- Severe hypoglycemia [48 hours]
Severe hypoglycemia is defined as blood glucose level less than 40 mg/dl.
- Number of patients needing rescue to insulin therapy protocol [48 hours]
- Number of adverse events occuring in the exenatide group [Day 30]
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 [Day 30]
- Postoperative morbidity [Day 30]
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 [48 hours]
- The coefficient of variability (GluCV) of blood glucose level [48 hours]
GluCV = GluSD*100/GluAve
- Mean number of blood glucose measured [48 hours]
- Mean difference between each blood glucose measurement and 120 mg/dl [48 hours]
- Perioperative cardiac mortality [Day 30]
- Perioperative non cardiac mortality [Day 30]
- Length of stay in intensive care unit [Day 30]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age over 18.
-
Patient consent.
-
Non insulin requiring type 2 diabetic patients.
-
Non diabetic patients.
-
Planned coronary artery bypass graft (CABG) surgery.
-
ASA (American Society of Anesthesiologists) score 1, 2, or 3.
Exclusion Criteria:
-
Pregnancy and breast feeding.
-
Pancreatectomy.
-
Acute pancreatitis.
-
Chronic pancreatitis.
-
Type 1 diabetic patients.
-
Insulin requiring type 2 patients.
-
HbA1c>8%
-
Ketoacidosis.
-
Hyperosmolar coma.
-
Preoperative blood glucose level above 300 mg/dl [21].
-
Insulin or exenatide contraindication.
-
History of renal transplantation or currently receiving renal dialysis or creatinine clearance below 60 ml/min.
-
Emergency surgery.
-
Planned non CABG cardiac surgery.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Post operative intensive care unit of the cardiac surgery department | Besançon | France | 25030 |
Sponsors and Collaborators
- Centre Hospitalier Universitaire de Besancon
- AstraZeneca
- Eli Lilly and Company
Investigators
- Principal Investigator: Guillaume Besch, MD, CHRU Besançon
- Study Director: Sébastien Pili-Floury, MD, PhD, CHRU Besançon
Study Documents (Full-Text)
None provided.More Information
Publications
- Galiatsatos P, Gibson BR, Rabiee A, Carlson O, Egan JM, Shannon RP, Andersen DK, Elahi D. The glucoregulatory benefits of glucagon-like peptide-1 (7-36) amide infusion during intensive insulin therapy in critically ill surgical patients: a pilot study. Crit Care Med. 2014 Mar;42(3):638-45. doi: 10.1097/CCM.0000000000000035.
- Goldberg PA, Sakharova OV, Barrett PW, Falko LN, Roussel MG, Bak L, Blake-Holmes D, Marieb NJ, Inzucchi SE. Improving glycemic control in the cardiothoracic intensive care unit: clinical experience in two hospital settings. J Cardiothorac Vasc Anesth. 2004 Dec;18(6):690-7.
- Studer C, Sankou W, Penfornis A, Pili-Floury S, Puyraveau M, Cordier A, Etievent JP, Samain E. Efficacy and safety of an insulin infusion protocol during and after cardiac surgery. Diabetes Metab. 2010 Feb;36(1):71-8. doi: 10.1016/j.diabet.2009.05.008. Epub 2010 Jan 25.
- API/2009/10