Exenatide for Stress Hyperglycemia

Stress Hyperglycemia Clinical Trial

— ExSTRESS  

Official title:

Intravenous Exenatide (Byetta®) Versus Insulin for Perioperative Glycemic Control in Cardiac Surgery: the Open-labeled Randomized Phase II/III ExStress Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01969149
• Other study ID #: API/2009/10
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 15, 2013
• Last updated: October 5, 2017
• Start date: January 2015
• Est. completion date: December 2016

Study information

• Verified date: March 2016
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: December 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperglycemia
• Stress Hyperglycemia

Intervention

Drug:
• Exenatide

• Insulin

Locations

Country	Name	City	State
France	Post operative intensive care unit of the cardiac surgery department	Besançon

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon	AstraZeneca, Eli Lilly and Company

Country where clinical trial is conducted

France, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl)	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.	48 hours
Secondary	Hypoglycemia	Hypoglycemia is defined as blood glucose level less than 80 mg/dl.	48 hours
Secondary	Severe hypoglycemia	Severe hypoglycemia is defined as blood glucose level less than 40 mg/dl.	48 hours
Secondary	Number of patients needing rescue to insulin therapy protocol		48 hours
Secondary	Number of adverse events occuring in the exenatide group	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).	Day 30
Secondary	Mortality		Day 30
Secondary	Postoperative morbidity	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.	Day 30
Secondary	The mean (GluAve) and standard deviation (GluSD) of blood glucose		48 hours
Secondary	The coefficient of variability (GluCV) of blood glucose level	GluCV = GluSD*100/GluAve	48 hours
Secondary	Mean number of blood glucose measured		48 hours
Secondary	Mean difference between each blood glucose measurement and 120 mg/dl		48 hours
Secondary	Perioperative cardiac mortality		Day 30
Secondary	Perioperative non cardiac mortality		Day 30
Secondary	Length of stay in intensive care unit		Day 30