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Intravenous Exenatide in Patients With Acute Brain Injury

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ClinicalTrials.gov Identifier: NCT02058940
Recruitment Status : Completed
First Posted : February 10, 2014
Results First Posted : July 12, 2018
Last Update Posted : July 12, 2018
Sponsor:
Collaborators:
AstraZeneca
Medtronic
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Tracking Information
First Submitted Date  ICMJE February 6, 2014
First Posted Date  ICMJE February 10, 2014
Results First Submitted Date  ICMJE June 1, 2018
Results First Posted Date  ICMJE July 12, 2018
Last Update Posted Date July 12, 2018
Study Start Date  ICMJE August 2015
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2018)
Percentage of Critically Ill Patients With Acute Brain Injury Achieving Pre-specified Feasibility Criteria [ Time Frame: Over 48 hours from infusion initiation ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 6, 2014)
Feasibility defined as the proportion 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 [ Time Frame: Over 48 hours from infusion initiation ]
Change History Complete list of historical versions of study NCT02058940 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2018)
  • Median Glucose Concentration During Exenatide Infusion [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Percentage of Glucose Measurements Within Goal Range [ Time Frame: Over 48 hours from infusion initiation ]
    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) [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Glycemic Variability [ Time Frame: Over 48 hours from infusion initiation ]
    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 [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from number of insulin units administered over 48 hours starting at infusion initiation
  • Percentage of Patients Requiring Rescue Insulin Infusion Protocol [ Time Frame: Over 48 hours from infusion initiation ]
    Defined as the percentage of patients requiring an insulin infusion to control glucose concentrations during exenatide treatment
  • Percentage of Hypoglycemic Episodes (<80 mg/dL) [ Time Frame: Over 48 hours from infusion initiation ]
    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) [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Percentage of Patients Experiencing Metabolic Crisis [ Time Frame: Over 48 hours from infusion initiation ]
    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 [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly measurements starting at infusion initiation over 48 hours
  • Median Daily Cerebral Perfusion Pressure [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly measurements starting at infusion initiation over 48 hours
  • Percentage of Hypotensive Episodes (SBP<100 mmHg) [ Time Frame: Over 48 hours from infusion initiation ]
    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) [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from blood pressure measurements starting at infusion initiation over 48 hours
  • Correlation of Exenatide Concentrations With Creatinine Clearance [ Time Frame: Over 48 hours from infusion initiation ]
    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 [ Time Frame: 24 hours ]
  • Exenatide Area Under the Concentration-time Curve After Discontinuation of Infusion [ Time Frame: 24 hours ]
  • Median Intensive Care Unit Length of Stay [ Time Frame: From enrollment to 30 days post study drug discontinuation ]
    Defined as the number of days admitted to the Intensive Care Unit
  • Median Hospital Length of Stay [ Time Frame: From enrollment to 30 days post study drug discontinuation ]
    Defined as the number of days admitted to the hospital
Original Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2014)
  • Mean glucose concentration during exenatide infusion [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Number of glucose measurements within goal (110-180 mg/dL)/total number of glucose measurements [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Mean time to reach glucose measurements within goal (110-180 mg/dL) [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Glycemic variability defined as the standard deviation of glucose [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Mean insulin use (units/kg body weight) [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from number of insulin units administered over 48 hours starting at infusion initiation
  • Proportion of subjects requiring rescue insulin infusion protocol [ Time Frame: Over 48 hours from infusion initiation ]
  • Number of hypoglycemic episodes (<80 mg/dL)/total number of glucose measurements [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Number of subjects with >1 episode of hypoglycemia (<80 mg/dL)/total number of subjects [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours
  • Proportion of patients experiencing metabolic crisis defined as cerebral microdialysate glucose concentration <0.7 mmol/L in combination with lactate pyruvate ratio >40 [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly microdialysis samples starting at infusion initiation over 48 hours
  • Mean daily intracranial and cerebral perfusion pressures [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly measurements starting at infusion initiation over 48 hours
  • Number of hypotensive episodes (SBP<100 mmHg)/total number of blood pressure measurements [ Time Frame: Over 48 hours from infusion initiation ]
    Calculated from hourly measurements starting at infusion initiation over 48 hours
  • Proportion of patients experiencing serious adverse events [ Time Frame: 30 days ]
    death, life-threatening event, prolonged hospitalization, disability or incapacity, congenital anomaly or birth defect, or important non-life threatening medical event
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravenous Exenatide in Patients With Acute Brain Injury
Official Title  ICMJE Intravenous Exenatide Infusion in Critically Ill Patients With Acute Brain Injury
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Injuries
Intervention  ICMJE Drug: Exenatide
50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Study Arms  ICMJE Experimental: Exenatide
Intervention: Drug: Exenatide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 6, 2014)
8
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2017
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02058940
Other Study ID Numbers  ICMJE 13-1391
Astra Zeneca Pharmaceuticals ( Other Grant/Funding Number: D5550L00025/ISSEXEN0038 )
Medtronic MiniMed, Inc ( Other Grant/Funding Number: NERP14-008 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE
  • AstraZeneca
  • Medtronic
Investigators  ICMJE
Principal Investigator: Nicole R. Pinelli, PharmD University of North Carolina, Chapel Hill
PRS Account University of North Carolina, Chapel Hill
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP