Intravenous Exenatide (Byetta®) Versus Insulin for Perioperative Glycemic Control in Cardiac Surgery: the Open-labeled Randomized Phase II/III ExStress Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Exenatide (Drug)
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.
干预措施: Insulin (Drug)
结局指标
主要结局
Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl)
时间窗: 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.
次要结局
- Mean difference between each blood glucose measurement and 120 mg/dl(48 hours)
- Perioperative non cardiac mortality(Day 30)
- Severe hypoglycemia(48 hours)
- The coefficient of variability (GluCV) of blood glucose level(48 hours)
- Mean number of blood glucose measured(48 hours)
- Length of stay in intensive care unit(Day 30)
- Hypoglycemia(48 hours)
- Number of patients needing rescue to insulin therapy protocol(48 hours)
- Perioperative cardiac mortality(Day 30)
- Mortality(Day 30)
- The mean (GluAve) and standard deviation (GluSD) of blood glucose(48 hours)
- Number of adverse events occuring in the exenatide group(Day 30)
- Postoperative morbidity(Day 30)