Exenatide for Stress Hyperglycemia (ExSTRESS)
Intravenous Exenatide (Byetta®) Versus Insulin for Perioperative Glycemic Control in Cardiac Surgery: the Open-labeled Randomized Phase II/III ExStress Study
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.
研究概览
详细说明
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.
研究类型
注册 (实际的)
阶段
- 阶段2
- 第三阶段
联系人和位置
学习地点
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Besançon、法国、25030
- Post operative intensive care unit of the cardiac surgery department
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：艾塞那肽组
艾塞那肽。 艾塞那肽：在治疗的第一个小时内推注 0.05 µg/min，然后连续输注 0.025 µg/min 直至治疗结束。 一旦测量到血糖水平高于 140 mg/dl，就会开始艾塞那肽治疗。 艾塞那肽将静脉注射。 治疗将在术后第一个 48 小时内在重症监护室进行，或者如果此事件发生得更早，直到重症监护室出院。 |
其他名称：
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有源比较器：胰岛素组
胰岛素：Humalog（赖脯胰岛素人类类似物）。 一旦测量到血糖水平高于 140 mg/dl，就会开始胰岛素治疗。 按照我们部门使用的胰岛素治疗方案，静脉输注的胰岛素剂量将根据血糖测量值进行调整。 我们部门使用的胰岛素治疗方案作为本研究的基准治疗，已在先前的研究中得到验证。 它源自 Goldberg 等人验证的协议。 |
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl)
大体时间：48 hours
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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
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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死亡
大体时间：第 30 天
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第 30 天
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Hypoglycemia
大体时间：48 hours
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Hypoglycemia is defined as blood glucose level less than 80 mg/dl.
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48 hours
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Severe hypoglycemia
大体时间：48 hours
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Severe hypoglycemia is defined as blood glucose level less than 40 mg/dl.
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48 hours
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Number of patients needing rescue to insulin therapy protocol
大体时间：48 hours
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48 hours
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Number of adverse events occuring in the exenatide group
大体时间：Day 30
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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).
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Day 30
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Postoperative morbidity
大体时间：Day 30
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Postoperative morbidity is defined as:
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Day 30
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The mean (GluAve) and standard deviation (GluSD) of blood glucose
大体时间：48 hours
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48 hours
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The coefficient of variability (GluCV) of blood glucose level
大体时间：48 hours
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GluCV = GluSD*100/GluAve
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48 hours
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Mean number of blood glucose measured
大体时间：48 hours
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48 hours
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Mean difference between each blood glucose measurement and 120 mg/dl
大体时间：48 hours
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48 hours
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Perioperative cardiac mortality
大体时间：Day 30
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Day 30
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Perioperative non cardiac mortality
大体时间：Day 30
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Day 30
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Length of stay in intensive care unit
大体时间：Day 30
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Day 30
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合作者和调查者
调查人员
- 首席研究员：Guillaume Besch, MD、CHRU Besançon
- 研究主任：Sébastien Pili-Floury, MD, PhD、CHRU Besançon
出版物和有用的链接
一般刊物
- 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.
- 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.
- 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.
- 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.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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