Intravenous Exenatide (Byetta) During Surgery

Hyperglycemia Clinical Trial

Official title:

Intravenous Exenatide (Byetta) for the Treatment of Perioperative Hyperglycemia: Rollover Phase I/II Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00882050
• Other study ID #: 808104
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2009
• Est. completion date: April 2016

Study information

• Verified date: December 2021
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

• Renal

• Preoperative serum Creatinine > 2.0 mg/dL

• Hepatic

• History of abnormal hepatic function in the past

• Hematologic

• Preoperative hematocrit (HCT) < 30%

• Platelet count < 100,000/mm3

• History of bleeding or clotting disorder

Related Conditions & MeSH terms

• Euglycemia
• Hyperglycemia
• Hypoglycemia

Intervention

Drug:
• Exenatide 0.27 ng/kg/min
Exenatide to be infused intravenously at 0.27 ng/kg/min (0.066 pmol/kg/min) for a duration of 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).
• Exenatide 0.41 ng/kg/min
Exenatide to be infused intravenously 0.41 ng/kg/min (0.099 pmol/kg/min) for a duration of 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).
• Placebo
Intravenous Placebo of NSS infused at same rate as drug 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).

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Thomas Jefferson University	Amylin Pharmaceuticals, LLC., Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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,	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.	Baseline and 90 minutes after starting infusion;