Trial Outcomes & Findings for Intravenous Exenatide (Byetta) During Surgery (NCT NCT00882050)
NCT ID: NCT00882050
Last Updated: 2022-01-21
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
104 participants
Primary outcome timeframe
Baseline and 90 minutes after starting infusion;
Results posted on
2022-01-21
Participant Flow
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.
Participant milestones
| Measure |
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).
* Blood will be collected prior to intubation and then 10 and 30 min after drug initiation and every 30 min (+or-2 min) until the IV is stopped and/or at extubation. Sample collection every 30 min post extubation for 2 hours, and once at 24 hours after extubation.
* Analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA) will be conducted.
|
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).
|
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).
|
|---|---|---|---|
|
Overall Study
STARTED
|
32
|
33
|
39
|
|
Overall Study
COMPLETED
|
31
|
33
|
39
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
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).
* Blood will be collected prior to intubation and then 10 and 30 min after drug initiation and every 30 min (+or-2 min) until the IV is stopped and/or at extubation. Sample collection every 30 min post extubation for 2 hours, and once at 24 hours after extubation.
* Analysis of GLP-1, Glucose, Potassium, Insulin, Glucagon, Epinephrine, Norepinephrine, Cortisol, and free fatty acids (FFA) will be conducted.
|
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).
|
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).
|
|---|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
Baseline Characteristics
Intravenous Exenatide (Byetta) During Surgery
Baseline characteristics by cohort
| Measure |
Exentatide 0.27 ng/kg/Min
n=32 Participants
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
|
Exentatide 0.41 ng/kg/Min
n=33 Participants
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
|
Placebo of IV NSS
n=39 Participants
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
|
Total
n=104 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
44 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
18 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
60 Participants
n=4 Participants
|
|
Age, Continuous
|
64.1 years
n=5 Participants
|
67.4 years
n=7 Participants
|
66.2 years
n=5 Participants
|
65.9 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
71 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
30 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
95 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
32 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
104 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and 90 minutes after starting infusion;Population: 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.
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.
Outcome measures
| Measure |
Exentatide 0.27 ng/kg/Min
n=32 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.
|
Exenatide 0.41ng/kg/Min
n=33 Participants
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.
|
Placebo IV NSS
n=39 Participants
Placebo: IV NSS to be infused by intravenous method at rate for experimental drug over 3 to 6 hours. Minimum 90 minutes.
|
|---|---|---|---|
|
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,
Pre glucose levels
|
112.3 mlg/dL
Standard Deviation 24.1
|
108.1 mlg/dL
Standard Deviation 27.8
|
110.4 mlg/dL
Standard Deviation 17.3
|
|
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,
at 90 minutes post infusion glucose levels
|
120.3 mlg/dL
Standard Deviation 36.3
|
125.0 mlg/dL
Standard Deviation 22.9
|
120.8 mlg/dL
Standard Deviation 29.7
|
Adverse Events
Exentatide 0.27 ng/kg/Min
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Exenatide 0.41ng/kg/Min
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo IV NSS
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Exentatide 0.27 ng/kg/Min
n=32 participants at risk
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.
|
Exenatide 0.41ng/kg/Min
n=33 participants at risk
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.
|
Placebo IV NSS
n=39 participants at risk
Placebo IV NSS to be at the rate of the experimental groups over 3-6 hours. Minimum 90 minutes post infusion.
|
|---|---|---|---|
|
Cardiac disorders
Ischemia
|
3.1%
1/32 • Number of events 1 • 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.
|
0.00%
0/33 • 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.
|
0.00%
0/39 • 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.
|
|
Vascular disorders
Left sided weakness
|
3.1%
1/32 • Number of events 1 • 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.
|
0.00%
0/33 • 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.
|
0.00%
0/39 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place