Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients

Phase 4

Terminated

• Conditions: Stress Hyperglycemia
• Interventions: Drug: Dulaglutide Injection; Other: Saline Injection

• Registration Number: NCT03743025
• Lead Sponsor: Emory University

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-11-14
• Study First Submitted QC: 2018-11-14
• Study First Posted: 2018-11-15
• Study Start: 2019-03-08
• Primary Completion: 2023-05-02
• Study Completion: 2023-05-02
• Status Verified: 2024-05
• Results First Submitted: 2024-05-02
• Results First Submitted QC: 2024-05-02
• Last Update Submitted: 2024-05-02
• Results First Posted: 2024-05-30
• Last Update Posted: 2024-05-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 28

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dulaglutide Arm	Dulaglutide Injection	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.
Placebo Arm	Saline Injection	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Grady Memorial Hospital; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

Emory Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States