Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients

This study is a prospective randomized study to examine the effects of exposure to dulaglutide on the prevention of stress-hyperglycemia and the metabolic inflammatory response in the perioperative period.

Study Overview

• Status: Terminated
• Conditions: Stress Hyperglycemia
• Intervention / Treatment: Drug: Dulaglutide Injection; Other: Saline Injection

Detailed Description

Stress hyperglycemia is common in the perioperative period and is associated with increased risk of death postoperatively. Counterregulatory hormones and inflammatory mediators appear to modulate the acute biological response to stress, however, the pathophysiological pathways that result in stress hyperglycemia and its link to poor clinical outcomes are not well understood. At least half of non-diabetes mellitus (DM) patients undergoing cardiac surgery develop stress hyperglycemia shown to be an independent risk factor of morbidity and mortality. The current approach to treat hyperglycemia with insulin has major limitations including high resource utilization and high risk of hypoglycemia. The main goals of this study are to examine baseline and postoperative metabolic profiles of non-diabetic, coronary artery bypass grafting (CABG) patients with stress hyperglycemia and to study the effect of a long-acting glucagon-like peptide-1 receptor agonists (GLP-1 RA) on the prevention of stress-hyperglycemia and modulation of metabolic stress during cardiac surgery.

To examine whether exposure to dulaglutide, a GLP-1 RA, can improve glycemic control and ameliorate the inflammatory response to acute surgical stress, obese patients without diabetes mellitus undergoing CABG surgery will be randomized to receive either dulaglutide or placebo two to three days prior to surgery. The researchers of this study ultimately want to provide evidence to support the use of novel therapies to prevent and manage stress hyperglycemia in the inpatient setting.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Atlanta, Georgia, United States, 30308
      • Emory Hospital Midtown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males or females between the ages of 40 and 80 years
• Body mass index (BMI) ≥25
• Undergoing elective CABG surgery
• No previous history of diabetes or hyperglycemia

Exclusion Criteria:

• Hyperglycemia (BG>125 mg/dl or HbA1c > 6.5%) or previous treatment with antidiabetic agents
• Impaired renal function (GFR < 30 ml/min) or clinically significant hepatic failure
• Gastrointestinal obstruction expected to require gastrointestinal suction
• Patients with clinically relevant pancreatic or gallbladder disease
• Treatment with oral or injectable corticosteroid
• Mental condition rendering the subject unable to understand the possible consequences of the study
• Pregnancy or breastfeeding at time of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dulaglutide Arm; Participants without a history of DM who are 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.	Drug: Dulaglutide Injection; Participants randomized at pre-surgery/anesthesia visit and without a history of DM will receive a single injection of Dulaglutide injection: 0.75 mg/0.5 mL solution in a single-dose pen 1 to 3 days prior to surgery; Other Names: Trulicity
Placebo Comparator: Placebo Arm; Participants without a history of DM who are 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.	Other: Saline Injection; Participants randomized at pre-surgery/anesthesia visit and without a history of DM will receive a single injection of Saline injection/0.5 mL pre-drawn solution 1 to 3 days prior to surgery; Other Names: Sodium Chloride Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Blood Glucose Levels (BG) > 140 mg/dl During Post Operative Period	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.	During the hospital stay (up to 12 days postoperatively)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Blood Glucose Levels During the Intensive Care Unit (ICU) Stay Postoperatively	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.	During the ICU stay (up to 7 days postoperatively)
Number of Participants Needing CII Treatment in the ICU	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.	During the ICU stay (up to 7 days postoperatively)
Number of Participants With Stress-hyperglycemia Requiring Rescue Therapy With Subcutaneous Insulin After Discontinuation of CII	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.	During the hospital stay (up to 12 days postoperatively)
Mean Blood Glucose Levels During the Hospital Stay	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.	During the hospital stay (up to 12 days postoperatively)
Mean Units Per Hour of Insulin 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.	During the ICU stay (up to 7 days postoperatively)
Mean Insulin Dose Per Day While in the ICU	The mean insulin dose during the time that participants were in the ICU is assessed as insulin units per day.	During the ICU stay (up to 7 days postoperatively)
Duration of Continuous Insulin Infusion (CII)	The duration of continuous insulin infusion (CII) is assessed in hours.	During the hospital stay (up to 12 days postoperatively)
Days of Subcutaneous (SC) Insulin 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.	During the hospital stay (up to 12 days postoperatively)
Amount of SC Insulin Administered	The amount of subcutaneous (SC) insulin administered during the ICU and non-ICU hospital stay, among participants requiring SC insulin after discontinuing CII.	During the hospital stay (up to 12 days postoperatively)
Number of Participants Experiencing Hyperglycemic Events	Hyperglycemic events are defined as BG > 200 mg/dl, during ICU and non-ICU hospital stay.	During the hospital stay (up to 12 days postoperatively)
Number of Participants Experiencing Hypoglycemic Events	Hypoglycemic events are defined as BG <70, < 54, and <40 mg/dl occurring during ICU and non-ICU hospital stay.	During the hospital stay (up to 12 days postoperatively)
Number of Participants Experiencing Mortality and Complications	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.	During the hospital stay (up to 12 days postoperatively)
Number of Participants Experiencing Gastrointestinal Adverse Events	The number participants who experienced gastrointestinal adverse events of nausea, vomiting, ileus, pancreatitis.	During the hospital stay (up to 12 days postoperatively)
ICU Length of Stay	ICU length of stay is assessed as the mean number of days participants in each study arm spent in the ICU.	During the ICU stay (up to 7 days postoperatively)
Hospital Length of Stay	Hospital length of stay is assessed as the mean number of days participants in each study arm spent in the hospital.	During the hospital stay (up to 12 days postoperatively)
Number of ICU Readmissions	The number of readmissions to the ICU.	During the hospital stay (up to 12 days postoperatively)
Number of Cerebrovascular Events	The number of cerebrovascular events.	During the hospital stay (up to 12 days postoperatively)
Participant Mortality	The number of participant deaths while in the ICU and hospital.	During the hospital stay (up to 12 days postoperatively)

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Francisco Pasquel, MD, MPH, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2019
• Primary Completion (Actual): May 2, 2023
• Study Completion (Actual): May 2, 2023

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 15, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Post Operative; Coronary Artery Bypass Surgery (CABG)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Dulaglutide
• Other Study ID Numbers: IRB00097963; 1K23GM128221-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes