Back to resultsIntravenous Exenatide in Patients With Acute Brain Injury
Primary Purpose
Brain Injuries
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Exenatide
Sponsored by
About this trial
This is an interventional treatment trial for Brain Injuries
Eligibility Criteria
Inclusion Criteria:
- Adults ≥18 years
- Acute brain injury resulting in admission to the Neurosciences Intensive Care Unit for an anticipated length of stay >48 hours
- Two Blood glucose concentrations > 150 mg/dL and ≤300 mg/dL
- Informed consent obtained via proxy
Exclusion Criteria:
- Pregnant (verified by urine or serum pregnancy test within 24 hours of initiation of infusion) or lactating females
- Type 1 diabetes mellitus
- History of pancreatitis or risk factors for acute pancreatitis (i.e ethanol abuse, gall stones)
- Renal insufficiency defined as creatinine clearance (CrCL) < 45 mL/min
- Known history of gastroparesis
- History of surgery on stomach, esophagus or duodenum
- Diabetic Ketoacidosis or Hyperosmolar Hyperglycemic Nonketotic Syndrome
- Concurrent steroid use or planned post-operative steroid use
- History of organ transplantation
- Brain death or suspected imminent brain death within the next 72 hours
- Refractory intracranial hypertension defined as intracranial pressure (ICP) > 25 mmHg for greater than 15 minutes and refractory to medical intervention
- Currently enrolled in another investigational drug or device protocol
- Insulin infusion within 3 hours of study drug administration or confirmed long acting insulin or sulfonylurea use prior to admission within 24 hours of study drug administration
- Known allergy to exenatide
Sites / Locations
- University of North Carolina; UNC Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Exenatide
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Critically Ill Patients With Acute Brain Injury Achieving Pre-specified Feasibility Criteria
Feasibility is defined as the percentage of patients 1) experiencing severe hypoglycemia (<40 mg/dL); 2) achieving glucose measurements within goal (110-180 mg/dL); and 3) experiencing nausea requiring discontinuation of exenatide therapy. The pre-specified criteria for determining feasibility includes the following: 1) at least 75% of patients achieving glucose measurements within goal (110-180 mg/dL) and 2) no more than 25% of patients experiencing severe hypoglycemia (<40 mg/dL) or nausea requiring exenatide discontinuation.
Secondary Outcome Measures
Median Glucose Concentration During Exenatide Infusion
Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Percentage of Glucose Measurements Within Goal Range
Percentage of glucose measurements within goal range is calculated as the number of glucose measurements within goal range (110-180 mg/dL) for all patients/total number of glucose measurements collected for all patients.
Median Time to Reach Glucose Measurements Within Goal Range (110-180 mg/dL)
Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Glycemic Variability
Glycemic variability is defined as the standard deviation of glucose calculated from hourly glucose measurements starting at infusion initiation over 48 hours
Median Insulin Use
Calculated from number of insulin units administered over 48 hours starting at infusion initiation
Percentage of Patients Requiring Rescue Insulin Infusion Protocol
Defined as the percentage of patients requiring an insulin infusion to control glucose concentrations during exenatide treatment
Percentage of Hypoglycemic Episodes (<80 mg/dL)
Percentage of hypoglycemic episodes is calculated as the total number of glucose measurements <80 mg/dL for all patients/total number of glucose measurements collected for all patients.
Percentage of Patients With >1 Episode of Hypoglycemia (<80 mg/dL)
Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Percentage of Patients Experiencing Metabolic Crisis
Metabolic crisis is defined as cerebral microdialysate glucose concentration <0.7 mmol/L in combination with lactate pyruvate ratio >40. Calculated from hourly microdialysis samples starting at infusion initiation over 48 hours
Median Daily Intracranial Pressure
Calculated from hourly measurements starting at infusion initiation over 48 hours
Median Daily Cerebral Perfusion Pressure
Calculated from hourly measurements starting at infusion initiation over 48 hours
Percentage of Hypotensive Episodes (SBP<100 mmHg)
Defined as the number of hypotensive episodes (SBP<100 mmHg)for all patients/total number of blood pressure measurements collected for all patients.
Percentage of Patients With >1 Episode of Hypotensive Episode (SBP<100 mmHg)
Calculated from blood pressure measurements starting at infusion initiation over 48 hours
Correlation of Exenatide Concentrations With Creatinine Clearance
Spearman's correlation coefficient calculated from exenatide concentrations and urine creatinine measurements collected for all patients during the study period. A correlation coefficient is a numerical measure of some type of correlation, meaning a statistical relationship between two variables. Spearman's correlation coefficient assumes values in the range from -1 to +1, where +1 indicates the strongest possible agreement and -1 the strongest possible disagreement.
Exenatide Elimination Rate Constant After Discontinuation of Infusion
Exenatide Area Under the Concentration-time Curve After Discontinuation of Infusion
Median Intensive Care Unit Length of Stay
Defined as the number of days admitted to the Intensive Care Unit
Median Hospital Length of Stay
Defined as the number of days admitted to the hospital
Full Information
NCT ID
NCT02058940
First Posted
February 6, 2014
Last Updated
July 11, 2018
Sponsor
University of North Carolina, Chapel Hill
Collaborators
AstraZeneca, Medtronic
1. Study Identification
Unique Protocol Identification Number
NCT02058940
Brief Title
Intravenous Exenatide in Patients With Acute Brain Injury
Official Title
Intravenous Exenatide Infusion in Critically Ill Patients With Acute Brain Injury
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
August 2015 (undefined)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
August 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
AstraZeneca, Medtronic
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the feasibility of exenatide infusion for the treatment of high blood sugars following acute brain injury.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Injuries
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Exenatide
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Exenatide
Intervention Description
50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Primary Outcome Measure Information:
Title
Percentage of Critically Ill Patients With Acute Brain Injury Achieving Pre-specified Feasibility Criteria
Description
Feasibility is defined as the percentage of patients 1) experiencing severe hypoglycemia (<40 mg/dL); 2) achieving glucose measurements within goal (110-180 mg/dL); and 3) experiencing nausea requiring discontinuation of exenatide therapy. The pre-specified criteria for determining feasibility includes the following: 1) at least 75% of patients achieving glucose measurements within goal (110-180 mg/dL) and 2) no more than 25% of patients experiencing severe hypoglycemia (<40 mg/dL) or nausea requiring exenatide discontinuation.
Time Frame
Over 48 hours from infusion initiation
Secondary Outcome Measure Information:
Title
Median Glucose Concentration During Exenatide Infusion
Description
Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Time Frame
Over 48 hours from infusion initiation
Title
Percentage of Glucose Measurements Within Goal Range
Description
Percentage of glucose measurements within goal range is calculated as the number of glucose measurements within goal range (110-180 mg/dL) for all patients/total number of glucose measurements collected for all patients.
Time Frame
Over 48 hours from infusion initiation
Title
Median Time to Reach Glucose Measurements Within Goal Range (110-180 mg/dL)
Description
Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Time Frame
Over 48 hours from infusion initiation
Title
Glycemic Variability
Description
Glycemic variability is defined as the standard deviation of glucose calculated from hourly glucose measurements starting at infusion initiation over 48 hours
Time Frame
Over 48 hours from infusion initiation
Title
Median Insulin Use
Description
Calculated from number of insulin units administered over 48 hours starting at infusion initiation
Time Frame
Over 48 hours from infusion initiation
Title
Percentage of Patients Requiring Rescue Insulin Infusion Protocol
Description
Defined as the percentage of patients requiring an insulin infusion to control glucose concentrations during exenatide treatment
Time Frame
Over 48 hours from infusion initiation
Title
Percentage of Hypoglycemic Episodes (<80 mg/dL)
Description
Percentage of hypoglycemic episodes is calculated as the total number of glucose measurements <80 mg/dL for all patients/total number of glucose measurements collected for all patients.
Time Frame
Over 48 hours from infusion initiation
Title
Percentage of Patients With >1 Episode of Hypoglycemia (<80 mg/dL)
Description
Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
Time Frame
Over 48 hours from infusion initiation
Title
Percentage of Patients Experiencing Metabolic Crisis
Description
Metabolic crisis is defined as cerebral microdialysate glucose concentration <0.7 mmol/L in combination with lactate pyruvate ratio >40. Calculated from hourly microdialysis samples starting at infusion initiation over 48 hours
Time Frame
Over 48 hours from infusion initiation
Title
Median Daily Intracranial Pressure
Description
Calculated from hourly measurements starting at infusion initiation over 48 hours
Time Frame
Over 48 hours from infusion initiation
Title
Median Daily Cerebral Perfusion Pressure
Description
Calculated from hourly measurements starting at infusion initiation over 48 hours
Time Frame
Over 48 hours from infusion initiation
Title
Percentage of Hypotensive Episodes (SBP<100 mmHg)
Description
Defined as the number of hypotensive episodes (SBP<100 mmHg)for all patients/total number of blood pressure measurements collected for all patients.
Time Frame
Over 48 hours from infusion initiation
Title
Percentage of Patients With >1 Episode of Hypotensive Episode (SBP<100 mmHg)
Description
Calculated from blood pressure measurements starting at infusion initiation over 48 hours
Time Frame
Over 48 hours from infusion initiation
Title
Correlation of Exenatide Concentrations With Creatinine Clearance
Description
Spearman's correlation coefficient calculated from exenatide concentrations and urine creatinine measurements collected for all patients during the study period. A correlation coefficient is a numerical measure of some type of correlation, meaning a statistical relationship between two variables. Spearman's correlation coefficient assumes values in the range from -1 to +1, where +1 indicates the strongest possible agreement and -1 the strongest possible disagreement.
Time Frame
Over 48 hours from infusion initiation
Title
Exenatide Elimination Rate Constant After Discontinuation of Infusion
Time Frame
24 hours
Title
Exenatide Area Under the Concentration-time Curve After Discontinuation of Infusion
Time Frame
24 hours
Title
Median Intensive Care Unit Length of Stay
Description
Defined as the number of days admitted to the Intensive Care Unit
Time Frame
From enrollment to 30 days post study drug discontinuation
Title
Median Hospital Length of Stay
Description
Defined as the number of days admitted to the hospital
Time Frame
From enrollment to 30 days post study drug discontinuation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults ≥18 years
Acute brain injury resulting in admission to the Neurosciences Intensive Care Unit for an anticipated length of stay >48 hours
Two Blood glucose concentrations > 150 mg/dL and ≤300 mg/dL
Informed consent obtained via proxy
Exclusion Criteria:
Pregnant (verified by urine or serum pregnancy test within 24 hours of initiation of infusion) or lactating females
Type 1 diabetes mellitus
History of pancreatitis or risk factors for acute pancreatitis (i.e ethanol abuse, gall stones)
Renal insufficiency defined as creatinine clearance (CrCL) < 45 mL/min
Known history of gastroparesis
History of surgery on stomach, esophagus or duodenum
Diabetic Ketoacidosis or Hyperosmolar Hyperglycemic Nonketotic Syndrome
Concurrent steroid use or planned post-operative steroid use
History of organ transplantation
Brain death or suspected imminent brain death within the next 72 hours
Refractory intracranial hypertension defined as intracranial pressure (ICP) > 25 mmHg for greater than 15 minutes and refractory to medical intervention
Currently enrolled in another investigational drug or device protocol
Insulin infusion within 3 hours of study drug administration or confirmed long acting insulin or sulfonylurea use prior to admission within 24 hours of study drug administration
Known allergy to exenatide
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicole R. Pinelli, PharmD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina; UNC Medical Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
12. IPD Sharing Statement
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Intravenous Exenatide in Patients With Acute Brain Injury
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