Trial Outcomes & Findings for Intravenous Exenatide in Patients With Acute Brain Injury (NCT NCT02058940)

NCT ID: NCT02058940

Last Updated: 2018-07-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 8 participants
• Primary outcome timeframe: Over 48 hours from infusion initiation
• Results posted on: 2018-07-12

Participant Flow

Participant milestones

Measure	Exenatide Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Overall Study STARTED	8
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Exenatide Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Overall Study Discharged from Critical Care Unit	1

Baseline Characteristics

Hunt and Hess Grade is only reported for patients with an admitting diagnosis of Subarachnoid Hemorrhage

Baseline characteristics by cohort

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Age, Continuous	64.0 years n=8 Participants
Sex: Female, Male Female	1 Participants n=8 Participants
Sex: Female, Male Male	7 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	3 Participants n=8 Participants
Race (NIH/OMB) White	4 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=8 Participants
Region of Enrollment United States	8 Participants n=8 Participants
Primary Admitting Diagnosis Intracerebral Hemorrhage	3 Participants n=8 Participants
Primary Admitting Diagnosis Acute Ischemic Stroke	3 Participants n=8 Participants
Primary Admitting Diagnosis Subarachnoid Hemorrhage	1 Participants n=8 Participants
Primary Admitting Diagnosis Subdural Hematoma	1 Participants n=8 Participants
Glasgow Coma Scale (GCS)	10.5 units on a scale n=8 Participants
Sequential Organ Failure Assessment (SOFA)	2.0 units on a scale n=8 Participants
Hunt and Hess Scale	2.0 units on a scale n=1 Participants • Hunt and Hess Grade is only reported for patients with an admitting diagnosis of Subarachnoid Hemorrhage
Modified Fisher Grade	3.0 units on a scale n=1 Participants • Modified Fisher Grade is only reported for patients with an admitting diagnosis of Subarachnoid Hemorrhage
Past Medical History Diabetes	4 Participants n=8 Participants
Past Medical History Hypertension	6 Participants n=8 Participants
Past Medical History Hyperlipidemia	4 Participants n=8 Participants
Past Medical History Cardiovascular Disease	5 Participants n=8 Participants
Past Medical History Chronic Kidney Disease	3 Participants n=8 Participants
Past Medical History Heart Failure	1 Participants n=8 Participants
Hemoglobin A1c (%)	6.5 percent n=8 Participants
Glucose	191.0 mg/dL n=8 Participants
Intensive Care Unit (ICU) Day of Study Drug Administration Day 1	4 Participants n=8 Participants
Intensive Care Unit (ICU) Day of Study Drug Administration Day 2	4 Participants n=8 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Percentage of Critically Ill Patients With Acute Brain Injury Achieving Pre-specified Feasibility Criteria Percentage Experiencing Severe Hypoglycemia	0 percentage of patients
Percentage of Critically Ill Patients With Acute Brain Injury Achieving Pre-specified Feasibility Criteria Percentage Achieving Glucose within Goal	87.5 percentage of patients
Percentage of Critically Ill Patients With Acute Brain Injury Achieving Pre-specified Feasibility Criteria Percentage with Nausea Requiring Discontinuation	0 percentage of patients

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Median Glucose Concentration During Exenatide Infusion	137.0 mg/dL Interval 118.0 to 164.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Percentage of Glucose Measurements Within Goal Range	69.6 percentage of measurements

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Median Time to Reach Glucose Measurements Within Goal Range (110-180 mg/dL)	200.0 minutes Interval 72.5 to 270.5

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Glycemic Variability	22.2 mg/dL Interval 15.0 to 36.3

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Calculated from number of insulin units administered over 48 hours starting at infusion initiation

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Median Insulin Use	0.03 units/kg Interval 0.0 to 0.3

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Defined as the percentage of patients requiring an insulin infusion to control glucose concentrations during exenatide treatment

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Percentage of Patients Requiring Rescue Insulin Infusion Protocol	0 percentage of patients

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Percentage of Hypoglycemic Episodes (<80 mg/dL)	1.2 percentage of measurements

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Calculated from hourly blood glucose samples starting at infusion initiation over 48 hours

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Percentage of Patients With >1 Episode of Hypoglycemia (<80 mg/dL)	12.5 percentage of patients

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Population: No patients received invasive intracranial multimodal monitoring as a part of their standard of care, as such, these endpoints were not collected.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Population: No patients with an admitting diagnosis of Subarachnoid Hemorrhage received ICP or CPP monitoring as part of standard of care and therefore data is not reported.

Calculated from hourly measurements starting at infusion initiation over 48 hours

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Population: No patients with an admitting diagnosis of Subarachnoid Hemorrhage received ICP or CPP monitoring as part of standard of care and therefore data is not reported.

Calculated from hourly measurements starting at infusion initiation over 48 hours

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Percentage of Hypotensive Episodes (SBP<100 mmHg)	1.2 percentage of measurements

SECONDARY outcome

Timeframe: Over 48 hours from infusion initiation

Calculated from blood pressure measurements starting at infusion initiation over 48 hours

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Percentage of Patients With >1 Episode of Hypotensive Episode (SBP<100 mmHg)	12.5 percentage of patients

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Exenatide n=7 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Correlation of Exenatide Concentrations With Creatinine Clearance	-0.2 correlation coefficient

SECONDARY outcome

Timeframe: 24 hours

Population: The institutional review board requested the study team limit exenatide concentration sampling to during the infusion. Samples were not collected after discontinuation of study drug. As such, this pharmacokinetic parameter is not reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours

Population: The institutional review board requested the study team limit exenatide concentration sampling to during the infusion. Samples were not collected after discontinuation of study drug. As such, this pharmacokinetic parameter is not reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From enrollment to 30 days post study drug discontinuation

Defined as the number of days admitted to the Intensive Care Unit

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Median Intensive Care Unit Length of Stay	9.0 days Interval 7.8 to 14.8

SECONDARY outcome

Timeframe: From enrollment to 30 days post study drug discontinuation

Defined as the number of days admitted to the hospital

Outcome measures

Measure	Exenatide n=8 Participants Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Median Hospital Length of Stay	12.5 days Interval 9.0 to 27.3

Adverse Events

Exenatide

Serious events: 3 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Measure	Exenatide n=8 participants at risk Exenatide: 50 ng/min IV for 30 minutes, then start 25 ng/min IV for a maximum duration of 48 hours
Nervous system disorders Death	37.5% 3/8 • From study enrollment to 30 days post discontinuation of Exenatide, up to 1 month

Other adverse events

Adverse event data not reported

Additional Information

Nicole R. Pinelli

The University of North Carolina at Chapel Hill

Phone: 919-962-1641

Email: nickipinelli@unc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place