Exenatide for Stress Hyperglycemia (ExSTRESS)

Centre Hospitalier Universitaire de Besancon

Status and phase: Completed; Phase 3; Phase 2

Conditions: Stress Hyperglycemia

Treatments: Drug: Insulin; Drug: Exenatide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01969149

API/2009/10

Details and patient eligibility

About

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.

Full 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.

Enrollment: 110 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 2 patient groups

Exenatide group

Experimental group

Description:

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.

Treatment:

Drug: Exenatide

Insulin group

Active Comparator group

Description:

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.

Treatment:

Drug: Insulin