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| Name | Class |
|---|---|
| Amylin Pharmaceuticals, LLC. | INDUSTRY |
| Eli Lilly and Company | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exentatide 0.27 ng/kg/min | Experimental | Exenatide to be infused by intravenous method at 0.27 ng/kg/min (0.066 pmol/kg/min) over 3-6 hours.
|
|
| Exentatide 0.41 ng/kg/min | Experimental | 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.
|
|
| Placebo IV NSS | Placebo Comparator | Placebo of IV normal saline solution as comparator.
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exenatide 0.27 ng/kg/min | Drug | Exenatide to be infused intravenously at 0.27 ng/kg/min (0.066 pmol/kg/min) for a duration of 3 to 6 hours.
|
| Measure | Description | Time Frame |
|---|---|---|
| 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; |
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Inclusion Criteria:
Exclusion Criteria:
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
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
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| Name | Affiliation | Role |
|---|---|---|
| Benjamin A. Kohl, MD | University of Pennsylvania | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
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Screening started in the appropriate surgical clinic on 3/29/2009 and continued until 5/14/2012 when Dr. Ben Kohl was recruited away from Penn. Recruitment resumed with Dr. Prakash Patel on 9/22/14 and ended 3/20/2015. During active enrollment 104 subjects were enrolled and an additional 96 potential subjects failed screening or declined.
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| ID | Title | Description |
|---|---|---|
| FG000 | Exentatide 0.27 ng/kg/Min | Exenatide IV 0.27 ng/kg/min (0.066 pmol/kg/min) over 3-6 hours. Induction of anesthesia will be equal to intubation time and drug will start (+ or-3 min).
|
| FG001 | 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.
|
| FG002 | Placebo IV NSS | Placebo of IV normal saline solution as comparator.
|
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Exentatide 0.27 ng/kg/Min | Demographics Exen 0.27 ng/kg/min Sex: Female 9 Male 23 Age , mean (SD) 64.1 (13.41) Race: African American: 2 Caucasian: 30 Ethnicity: Non-Hispanic 32 |
| BG001 | Exentatide 0.41 ng/kg/Min |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 104 subjects were enrolled. 39 subjects randomized to placebo, 32 in 0.27 ng/kg/min, and 33 to 41 ng/kg/minute. One subject was removed from the study at the request of the surgeon. No intraoperative blinded infusions (study drug) were discontinued in any other case. | Posted | Mean | Standard Deviation | mlg/dL | Baseline and 90 minutes after starting infusion; |
|
AEs were collected on each subject from time of signed consent until 24 hours post surgery. This time frame was approximately one month.
Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Minimum 90 minutes post infusion. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ischemia | Cardiac disorders | MedDRA (10.0) | Systematic Assessment | Study drug had infused about 1 hour when surgery was stopped due to concern of ischemia on telemetry (prior history). Subject was ruled out for myocardial infarction (3 sets cardiac enzymes negative). Released next day. Not related to study drug. |
Change in PI during the trial led to intermittent study activitity and a delay in enrollment which prolonged the study and final data entry.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kim Lacy, RN BSN | University of Pennsylvania | 215-893-7234 | kim.lacy@uphs.upenn.edu |
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| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| D006943 | Hyperglycemia |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077270 | Exenatide |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
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|
|
|
| Exenatide 0.41 ng/kg/min | Drug | 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).
|
|
|
| Placebo | Drug | 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).
|
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Table 1: Demographics Exen 0.41 ng/kg/min
Sex: Female 13 Male 20 Age , mean (SD) 67.4 (11.98) Race: African American: 2 Caucasian: 31 Ethnicity: Non-Hispanic 33
| BG002 | Placebo of IV NSS | Table 1: Demographics placebo Sex: Female 11 Male 28 Age, mean (SD) 66.2 (13.56) Race: African American: 5 Caucasian: 34 Ethnicity: Non-Hispanic 39 |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Experimental: IV Exenatide to be infused by intravenous method at 0.27 ng/kg/min (0.099 pmol/kg/min) over 3 to 6 hours. Minimum time of infusion 90 minutes. |
| OG001 | Exenatide 0.41ng/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. Minimum time of infusion 90 minutes. |
| OG002 | Placebo IV NSS | Placebo: IV NSS to be infused by intravenous method at rate for experimental drug over 3 to 6 hours. Minimum 90 minutes. |
|
|
|
| 0 |
| 32 |
| 0 |
| 32 |
| 2 |
| 32 |
| EG001 | Exenatide 0.41ng/kg/Min | Exenatide to be infused by intravenous method at 0.41 ng/kg/min (0.066 pmol/kg/min) over 3-6 hours. Minimum 90 minutes post infusion. | 0 | 33 | 0 | 33 | 0 | 33 |
| EG002 | Placebo IV NSS | Placebo IV NSS to be at the rate of the experimental groups over 3-6 hours. Minimum 90 minutes post infusion. | 0 | 39 | 0 | 39 | 0 | 39 |
|
| Left sided weakness | Vascular disorders | MedDRA (10.0) | Systematic Assessment | Left sided weakness 30 hrs post op (AVR). Had CT scan & neurology consult. Probable subacute infarct in right frontal lobe. No significant mass effect, no hemorrhage. Subject monitored, recovered fully prior to discharge. Not related to study drug. |
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| D014118 |
| Toxins, Biological |
| D001685 | Biological Factors |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |