Clinical trial NCT01969149: Exenatide for Stress Hyperglycemia
Official title: Intravenous Exenatide (Byetta®) Versus Insulin for Perioperative Glycemic Control in Cardiac Surgery: the Open-labeled Randomized Phase II/III ExStress Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Stress Hyperglycemia
Keywords: Stress Hyperglycemia
Perioperative glycemic control
Cardiac surgery
Coronary artery bypass surgery
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Eli Lilly and Company
First posted: 2013-10-25
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl)
timeFrame: 48 hours
Secondary outcomes:
measure: Hypoglycemia
timeFrame: 48 hours
measure: Severe hypoglycemia
timeFrame: 48 hours
measure: Number of patients needing rescue to insulin therapy protocol
timeFrame: 48 hours
measure: Number of adverse events occuring in the exenatide group
timeFrame: Day 30
measure: Mortality
timeFrame: Day 30
measure: Postoperative morbidity
timeFrame: Day 30
measure: The mean (GluAve) and standard deviation (GluSD) of blood glucose
timeFrame: 48 hours
measure: The coefficient of variability (GluCV) of blood glucose level
timeFrame: 48 hours
measure: Mean number of blood glucose measured
timeFrame: 48 hours
measure: Mean difference between each blood glucose measurement and 120 mg/dl
timeFrame: 48 hours
measure: Perioperative cardiac mortality
timeFrame: Day 30
measure: Perioperative non cardiac mortality
timeFrame: Day 30
measure: Length of stay in intensive care unit
timeFrame: Day 30
Other outcomes:
Locations:
city: Besançon
country: France
facility: Post operative intensive care unit of the cardiac surgery department
Study officials:
affiliation: CHRU Besançon
name: Guillaume Besch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU Besançon
name: Sébastien Pili-Floury, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1053/j.jvca.2004.08.003.
citation: 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.
citation: 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.
citation: Besch G, Perrotti A, Salomon du Mont L, Puyraveau M, Ben-Said X, Baltres M, Barrucand B, Flicoteaux G, Vettoretti L, Samain E, Chocron S, Pili-Floury S. Impact of intravenous exenatide infusion for perioperative blood glucose control on myocardial ischemia-reperfusion injuries after coronary artery bypass graft surgery: sub study of the phase II/III ExSTRESS randomized trial. Cardiovasc Diabetol. 2018 Nov 1;17(1):140. doi: 10.1186/s12933-018-0784-y.