Trial Outcomes & Findings for Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients (NCT NCT03743025)

NCT ID: NCT03743025

Last Updated: 2024-05-30

Results Overview

Stress-hyperglycemia is defined as any post-CABG hospital-obtained blood glucose (BG) levels \>140 milligrams per deciliter (mg/dL). Information on BG measurements was collected both at bedside by glucose meter and by hospital laboratory. BG was measured every 1-2 hours during continuous insulin infusion (CII) in the ICU, and before meals and at bedtime after transition to regular wards.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 28 participants
• Primary outcome timeframe: During the hospital stay (up to 12 days postoperatively)
• Results posted on: 2024-05-30

Participant Flow

Participants were recruited from Grady Memorial Hospital, Emory University Hospital Midtown, and Emory University Hospital in Atlanta, Georgia, USA. Participant enrollment began March 8, 2019 and the final study assessment occurred on May 2, 2023.

Participant milestones

Measure	Dulaglutide Participants without a history of diabetes mellitus (DM) who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to elective coronary artery bypass graft (CABG) surgery.	Placebo Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to elective CABG surgery.
Overall Study STARTED	14	14
Overall Study COMPLETED	12	13
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	Dulaglutide Participants without a history of diabetes mellitus (DM) who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to elective coronary artery bypass graft (CABG) surgery.	Placebo Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to elective CABG surgery.
Overall Study Surgery was cancelled	2	1

Baseline Characteristics

Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients

Baseline characteristics by cohort

Measure	Dulaglutide n=14 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=14 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.	Total n=28 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
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	58.00 years STANDARD_DEVIATION 11.62 • n=5 Participants	61.50 years STANDARD_DEVIATION 10.86 • n=7 Participants	59.40 years STANDARD_DEVIATION 10.87 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

Stress-hyperglycemia is defined as any post-CABG hospital-obtained blood glucose (BG) levels >140 milligrams per deciliter (mg/dL). Information on BG measurements was collected both at bedside by glucose meter and by hospital laboratory. BG was measured every 1-2 hours during continuous insulin infusion (CII) in the ICU, and before meals and at bedtime after transition to regular wards.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of Participants With Blood Glucose Levels (BG) > 140 mg/dl During Post Operative Period	11 Participants	13 Participants

SECONDARY outcome

Timeframe: During the ICU stay (up to 7 days postoperatively)

Population: This analysis includes participants who completed the study.

To measure glucose control, the mean blood glucose levels in mg/dL were measured during the postoperative Intensive Care Unit (ICU) stay. Information on BG measurements was collected both at bedside by glucose meter and by hospital laboratory. BG was measured every 1-2 hours during continuous insulin infusion (CII) in the ICU, and before meals and at bedtime after transition to regular wards.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Mean Blood Glucose Levels During the Intensive Care Unit (ICU) Stay Postoperatively	134.11 mg/dL Standard Deviation 14.00	129.79 mg/dL Standard Deviation 11.42

SECONDARY outcome

Timeframe: During the ICU stay (up to 7 days postoperatively)

Population: This analysis includes participants who completed the study.

Patients with two consecutive BG >180 mg/dl, or average daily BG >180 mg/dl were started on rescue therapy with subcutaneous basal insulin (glargine or levemir) once daily. Information on BG measurements was collected both at bedside by glucose meter and by hospital laboratory. BG was measured every 1-2 hours during continuous insulin infusion (CII) in the ICU, and before meals and at bedtime after transition to regular wards. The number of participants needing CII while in the ICU postoperatively was compared between patients randomized to dulaglutide or placebo study arms.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of Participants Needing CII Treatment in the ICU	11 Participants	12 Participants

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who required CII while in the ICU.

Patients with two consecutive BG >180 mg/dl, or an average daily BG >180 mg/dl were started on rescue therapy with subcutaneous basal insulin (glargine or levemir) once daily. Information on BG measurements was collected both at bedside by glucose meter and by hospital laboratory. BG was measured every 1-2 hours during continuous insulin infusion (CII) in the ICU, and before meals and at bedtime after transition to regular wards. The number of participants in need of rescue therapy with subcutaneous insulin postoperatively, after CII was discontinued, was compared between study arms.

Outcome measures

Measure	Dulaglutide n=11 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=12 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of Participants With Stress-hyperglycemia Requiring Rescue Therapy With Subcutaneous Insulin After Discontinuation of CII	6 Participants	4 Participants

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

To measure glucose control, the mean blood glucose levels in mg/dL during the non-ICU hospital stay postoperatively were measured. Information on BG measurements was collected both at bedside by glucose meter and by hospital laboratory. BG was measured every 1-2 hours during continuous insulin infusion (CII) in the ICU, and before meals and at bedtime after transition to regular wards.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Mean Blood Glucose Levels During the Hospital Stay	119.69 mg/dL Standard Deviation 23.50	117.69 mg/dL Standard Deviation 20.59

SECONDARY outcome

Timeframe: During the ICU stay (up to 7 days postoperatively)

Population: This analysis includes participants who required CII while in the ICU.

The mean insulin dose during the time that participants were in the ICU is assessed as insulin infusion units per hour.

Outcome measures

Measure	Dulaglutide n=11 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=12 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Mean Units Per Hour of Insulin While in the ICU	2.89 insulin units/hour Standard Deviation 2.60	2.01 insulin units/hour Standard Deviation 0.98

SECONDARY outcome

Timeframe: During the ICU stay (up to 7 days postoperatively)

Population: This analysis includes participants who required CII while in the ICU.

The mean insulin dose during the time that participants were in the ICU is assessed as insulin units per day.

Outcome measures

Measure	Dulaglutide n=11 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=12 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Mean Insulin Dose Per Day While in the ICU	61.15 insulin units/day Standard Deviation 66.84	33.01 insulin units/day Standard Deviation 20.19

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who required CII while in the ICU.

The duration of continuous insulin infusion (CII) is assessed in hours.

Outcome measures

Measure	Dulaglutide n=11 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=12 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Duration of Continuous Insulin Infusion (CII)	18.90 hours Standard Deviation 5.60	16.69 hours Standard Deviation 6.31

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who required CII while in the ICU and subsequent SC after discontinuation of CII.

Subcutaneous (SC) insulin use after continuous insulin infusion (CII) is discontinued is assessed as the number of days that SC insulin was required.

Outcome measures

Measure	Dulaglutide n=6 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=4 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Days of Subcutaneous (SC) Insulin After Discontinuation of CII	2.00 days Standard Deviation 1.09	3.50 days Standard Deviation 2.08

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who required CII while in the ICU and subsequent SC after discontinuation of CII.

The amount of subcutaneous (SC) insulin administered during the ICU and non-ICU hospital stay, among participants requiring SC insulin after discontinuing CII.

Outcome measures

Measure	Dulaglutide n=6 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=4 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Amount of SC Insulin Administered	8.25 units of insulin Standard Deviation 14.28	10.92 units of insulin Standard Deviation 10.44

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

Hyperglycemic events are defined as BG > 200 mg/dl, during ICU and non-ICU hospital stay.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of Participants Experiencing Hyperglycemic Events	1 Participants	2 Participants

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

Hypoglycemic events are defined as BG <70, < 54, and <40 mg/dl occurring during ICU and non-ICU hospital stay.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of Participants Experiencing Hypoglycemic Events BG <70 mg/dL	0 Participants	0 Participants
Number of Participants Experiencing Hypoglycemic Events BG <54 mg/dL	0 Participants	0 Participants
Number of Participants Experiencing Hypoglycemic Events BG <40 mg/dL	0 Participants	0 Participants

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

The number of participants experiencing a composite of mortality and complications. Complications include sternal wound infection, bacteremia, pneumonia, acute kidney injury, and acute myocardial infarction.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of Participants Experiencing Mortality and Complications	2 Participants	1 Participants

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

The number participants who experienced gastrointestinal adverse events of nausea, vomiting, ileus, pancreatitis.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of Participants Experiencing Gastrointestinal Adverse Events	3 Participants	1 Participants

SECONDARY outcome

Timeframe: During the ICU stay (up to 7 days postoperatively)

Population: This analysis includes participants who completed the study.

ICU length of stay is assessed as the mean number of days participants in each study arm spent in the ICU.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
ICU Length of Stay	2.19 days Standard Deviation 1.45	2.76 days Standard Deviation 1.59

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

Hospital length of stay is assessed as the mean number of days participants in each study arm spent in the hospital.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Hospital Length of Stay	7.25 days Standard Deviation 2.92	8.92 days Standard Deviation 3.72

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

The number of readmissions to the ICU.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of ICU Readmissions	0 ICU readmissions	0 ICU readmissions

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

The number of cerebrovascular events.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Number of Cerebrovascular Events	0 cerebrovascular events	0 cerebrovascular events

SECONDARY outcome

Timeframe: During the hospital stay (up to 12 days postoperatively)

Population: This analysis includes participants who completed the study.

The number of participant deaths while in the ICU and hospital.

Outcome measures

Measure	Dulaglutide n=12 Participants Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 Participants Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Participant Mortality ICU deaths	0 Participants	0 Participants
Participant Mortality Non-ICU hospital deaths	0 Participants	0 Participants

Adverse Events

Dulaglutide

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dulaglutide n=12 participants at risk Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 participants at risk Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Renal and urinary disorders Hospital readmission due to nausea and vomitting, acute kidney injury, and dehydration	8.3% 1/12 • Information on adverse events was collected among participants who had elective CABG surgery, beginning at the time of consent and continued through the final assessment occurring 30 days after discharge from the hospital, up to 42 days postoperatively. Information was collected for the following specific adverse events:sternal wound infection, bacteremia, pneumonia, acute kidney injury, acute myocardial infarction, nausea, vomiting, ileus, and pancreatitis.	0.00% 0/13 • Information on adverse events was collected among participants who had elective CABG surgery, beginning at the time of consent and continued through the final assessment occurring 30 days after discharge from the hospital, up to 42 days postoperatively. Information was collected for the following specific adverse events:sternal wound infection, bacteremia, pneumonia, acute kidney injury, acute myocardial infarction, nausea, vomiting, ileus, and pancreatitis.

Other adverse events

Measure	Dulaglutide n=12 participants at risk Participants without a history of DM who were randomized to receive a single injection of dulaglutide (0.75 mg/0.5 mL solution in a single-dose pen) one to three days prior to surgery.	Placebo n=13 participants at risk Participants without a history of DM who were randomized to receive a single injection of a placebo (saline injection of 0.5 mL pre-drawn solution) one to three days prior to surgery.
Gastrointestinal disorders Nausea	16.7% 2/12 • Information on adverse events was collected among participants who had elective CABG surgery, beginning at the time of consent and continued through the final assessment occurring 30 days after discharge from the hospital, up to 42 days postoperatively. Information was collected for the following specific adverse events:sternal wound infection, bacteremia, pneumonia, acute kidney injury, acute myocardial infarction, nausea, vomiting, ileus, and pancreatitis.	7.7% 1/13 • Information on adverse events was collected among participants who had elective CABG surgery, beginning at the time of consent and continued through the final assessment occurring 30 days after discharge from the hospital, up to 42 days postoperatively. Information was collected for the following specific adverse events:sternal wound infection, bacteremia, pneumonia, acute kidney injury, acute myocardial infarction, nausea, vomiting, ileus, and pancreatitis.
Renal and urinary disorders Acute kidney injury	16.7% 2/12 • Information on adverse events was collected among participants who had elective CABG surgery, beginning at the time of consent and continued through the final assessment occurring 30 days after discharge from the hospital, up to 42 days postoperatively. Information was collected for the following specific adverse events:sternal wound infection, bacteremia, pneumonia, acute kidney injury, acute myocardial infarction, nausea, vomiting, ileus, and pancreatitis.	7.7% 1/13 • Information on adverse events was collected among participants who had elective CABG surgery, beginning at the time of consent and continued through the final assessment occurring 30 days after discharge from the hospital, up to 42 days postoperatively. Information was collected for the following specific adverse events:sternal wound infection, bacteremia, pneumonia, acute kidney injury, acute myocardial infarction, nausea, vomiting, ileus, and pancreatitis.

Additional Information

Dr. Francisco J. Pasquel

Emory University

Phone: 404-778-1695

Email: fpasque@emory.edu

Results disclosure agreements

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