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Intravenous Exenatide (Byetta) During Surgery

Primary Purpose

Euglycemia, Hypoglycemia, Hyperglycemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Exenatide 0.27 ng/kg/min

Exenatide 0.41 ng/kg/min

Placebo

About this trial

This is an interventional treatment trial for Euglycemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Exentatide 0.27 ng/kg/min

Exentatide 0.41 ng/kg/min

Placebo IV NSS

Arm Description

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).

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00882050

First Posted

April 15, 2009

Last Updated

December 21, 2021

Sponsor

Thomas Jefferson University

Collaborators

Amylin Pharmaceuticals, LLC., Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00882050

Brief Title

Intravenous Exenatide (Byetta) During Surgery

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

March 2009 (undefined)

Primary Completion Date

April 2016 (Actual)

Study Completion Date

April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Thomas Jefferson University

Collaborators

Amylin Pharmaceuticals, LLC., Eli Lilly and Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Euglycemia, Hypoglycemia, Hyperglycemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

104 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Exentatide 0.27 ng/kg/min

Arm Type

Experimental

Arm Description

Arm Title

Exentatide 0.41 ng/kg/min

Arm Type

Experimental

Arm Description

Arm Title

Placebo IV NSS

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Exenatide 0.27 ng/kg/min

Other Intervention Name(s)

Byetta

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Exenatide 0.41 ng/kg/min

Other Intervention Name(s)

Byetta

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Normal Saline Solution

Intervention Description

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).

Primary Outcome Measure Information:

Title

Description

Time Frame

Baseline and 90 minutes after starting infusion;

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benjamin A. Kohl, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Study Director

Facility Information:

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

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Intravenous Exenatide (Byetta) During Surgery

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