Intravenous Exenatide (Byetta) for the Treatment of Perioperative Hyperglycemia: Rollover Phase I/II Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- The Primary Objective is to Determine the Ability of Intravenous Exenatide to: Maintain Intraoperative Euglycemia in Subjects With Initial Blood Glucose < 126 mg/dL in Surgical Subjects as Compared to Placebo,
研究概览
简要总结
The purpose of this project is to study if intravenous Exenatide is effective at maintaining normal blood glucose levels and preventing low blood glucose levels during surgery.
详细描述
This is a single-center, block randomized, double-blind, placebo-controlled, dose-ranging study. Subjects will be randomized in equal proportions to one of three treatment arms: placebo of normal saline solution, 0.27 ng/kg/min (0.066 pmol/kg/min) IV Exenatide, and 0.41 ng/kg/min (0.099 pmol/kg/min) IV Exenatide. We will use a block number of 30 (please see power analysis) so that balance between each of the three groups will be maintained over the enrollment period. We will stratify the randomization scheme to ensure balance of diabetics and non-diabetics within the groups.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age (>18 years)
- •Weight of > 50 kg and < 150 kg
- •Ability to provide informed consent
- •Elective surgery including:
- •Cardiac surgery to include elective CABG with or without single or multivalve repair or replacement and/or single or multivalve repair/replacement requiring CPB and sternotomy (to include subjects who are undergoing first time or redo cardiac surgery)
- •Abdominal aortic aneurysm repair
- •Carotid endarterectomy
- •Esophagectomy
- •Cystectomy
- •Nephrectomy
- •If female, subject must be non-lactating, and, if of childbearing potential, must have a negative urine pregnancy test within 24 hours prior to receiving study drug
排除标准
- •Age (<18 years)
- •Inability to provide informed consent
- •History or risk of pancreatitis (e.g. ethanol abuse, gall stones)
- •Receipt of an investigational drug or device with 30 days prior to surgery
- •Use of any concomitant medication listed above on the day of surgery
- •Known allergy to Exenatide, fentanyl, midazolam, isoflurane, propofol, heparin or neuromuscular blockers
- •Known substance abuse
- •Surgical procedure other than:
- •Cardiac surgery to include elective CABG with or without single or multivalve repair or replacement and/or single or multivalve repair/ replacement requiring CPB and sternotomy (to include subjects who are undergoing first time or redo cardiac surgery)
- •Abdominal aortic aneurysm repair
- •Carotid endarterectomy
- •Esophagectomy
- •Cystectomy
- •Nephrectomy
- •Insulin dependent diabetes mellitis
- •Anticipated administration of intraoperative steroids
- •Major end organ dysfunction, defined as:
- •Current intravenous inotropic agents
- •Preoperative use of intra-aortic balloon pump (IABP), left ventricular assist device (LVAD), or extracorporeal membrane oxygenation (ECMO)
- •Preoperative serum Creatinine > 2.0 mg/dL
- •History of abnormal hepatic function in the past
- •Hematologic
- •Preoperative hematocrit (HCT) < 30%
- •Platelet count < 100,000/mm3
- •History of bleeding or clotting disorder
研究组 & 干预措施
Exentatide 0.27 ng/kg/min
Exenatide to be infused by intravenous method at 0.27 ng/kg/min (0.066 pmol/kg/min) over 3-6 hours.
- Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes).
- Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation.
- Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).
干预措施: Exenatide 0.27 ng/kg/min (Drug)
Exentatide 0.41 ng/kg/min
Experimental: IV Exenatide to be infused by intravenous method at 0.41 ng/kg/min (0.099 pmol/kg/min) over 3 to 6 hours.
- Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes).
- Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation.
- Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin,Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).
干预措施: Exenatide 0.41 ng/kg/min (Drug)
Placebo IV NSS
Placebo of IV normal saline solution as comparator.
- Induction of anesthesia will be equal to Intubation time. Infusion will begin at this time point (+ or - 3 minutes).
- Blood samples will be obtained prior to intubation and then 10 and 30 minutes after drug initiation and every 30 minutes (+ or - 2 minutes) thereafter until the infusion is stopped. The drug infusion will be stopped at extubation. Blood will then be sampled every 30 minutes (+ or - 2 minutes) post extubation for 2 hours, and once 24 hours after extubation.
- Blood plasma levels will be collected (8-10 mls) for analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA).
干预措施: Placebo (Drug)
结局指标
主要结局
The Primary Objective is to Determine the Ability of Intravenous Exenatide to: Maintain Intraoperative Euglycemia in Subjects With Initial Blood Glucose < 126 mg/dL in Surgical Subjects as Compared to Placebo,
时间窗: Baseline and 90 minutes after starting infusion;
Logistic regression analysis will be utizlized to determine maintenance of euglycemia (yes v no) for our primary analysis. A standard area under the curve (AUC) analysis will be performed for each time point to map out drug deposition. Assuming a standard 2 compartment model, 10 subjects per group is sufficient to accurately predict mean AUC. Our primary analysis should provide ample statistical power.
次要结局
未报告次要终点