Impact of Perioperative Exenatide Infusion on Quality of Life in Cardiac Surgery Patients

Study Overview
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Brief Summary
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A diminution of quality of life is often reported by patients after coronary artery bypass graft (CABG) surgery. A part of this diminution could be explain by postoperative left ventricular (LV) dysfunction. Exenatide (Byetta®) is an incretin mimetic, characterized by an anti-hyperglycemic effect that depends on the blood glucose level. Recent data have suggested that exenatide could improve LV function by an inotropic effect in patients suffering from cardiogenic shock or from congestive heart failure. Moreover, patients suffering from congestive heart failure reported a better quality of life when they were treated with exenatide compared to placebo. The investigators hypothesize that perioperative exenatide infusion could improve postoperative quality of life in CABG surgery patients.

Detailed Description
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The ExeQOL study is an ancillary study of the ExSTRESS trial (www.clinicaltrials.gov identifier: NCT01969149). The ExSTRESS trial is a phase II/III randomized-controlled trial that aim at assessing intravenous exenatide versus insulin for perioperative glycemic control in CABG surgery. The phase II of the ExStress trial 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. The aim of the phase III of the ExSTRESS trial is to 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.

Official Title
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Impact of Intravenous Exenatide Versus Insulin on Quality of Life in Cardiac Surgery Patients: an Ancillary Study of the ExSTRESS Phase II/III Clinical Trial

Conditions
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Quality of Life

Intervention / Treatment
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* Drug: Exenatide
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide group<br>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<br>* 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.<br>* Other names: Incretin;|
| Active Comparator: Insulin group<br>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<br>* 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.<br>* Other names: Human Analog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of the SF-36 score value at 3-months | The SF-36 score is a self-administered questionnaire that assess both the physical and the psychosocial health-related quality of life. The use of the SF-36 score is recommended by the French Health Authority in coronary patients. The variation of the SF-36 score value at 3-months is defined as the difference between the SF36-score value at 3 months minus the preoperative SF-36 score value. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of the SF-36 score value at 1-month | The SF-36 score is a self-administered questionnaire that assess both the physical and the psychosocial health-related quality of life. The use of the SF-36 score is recommended by the French Health Authority in coronary patients. The variation of the SF-36 score value at 1-month is defined as the difference between the SF36-score value at 1 month minus the preoperative SF-36 score value. | 1 month | 
| Variation of the SF-36 score value at 6-months | The SF-36 score is a self-administered questionnaire that assess both the physical and the psychosocial health-related quality of life. The use of the SF-36 score is recommended by the French Health Authority in coronary patients. The variation of the SF-36 score value at 6-months is defined as the difference between the SF36-score value at 6 months minus the preoperative SF-36 score value. | 6 months | 
| Variation of the SF-36 score value at 12-months | The SF-36 score is a self-administered questionnaire that assess both the physical and the psychosocial health-related quality of life. The use of the SF-36 score is recommended by the French Health Authority in coronary patients. The variation of the SF-36 score value at 12-months is defined as the difference between the SF36-score value at 12 months minus the preoperative SF-36 score value. | 12 months | 
| 1-month mortality |  | 1 month | 
| 3-months mortality |  | 3 months | 
| 6-months mortality |  | 6 month | 
| 12-months mortality |  | 12 months | 
| Postoperative left ventricular function | Left ventricular function will be assessed during a transthoracic echocardiography performed at Day 7. Left ventricular ejection fraction and filling pressure will be measured during this procedure. | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Quality of Life, Cardiac Surgery, Coronary Artery Bypass Graft Surgery, Incretin mimetic, Exenatide