Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients

Stress Hyperglycemia Clinical Trial

Official title:

Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03743025
• Other study ID #: IRB00097963
• Secondary ID: 1K23GM128221-01A
• Status: Terminated
• Phase: Phase 4
• Start date: March 8, 2019
• Est. completion date: May 2, 2023

Study information

• Verified date: May 2024
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: May 2, 2023
• Est. primary completion date: May 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperglycemia
• Stress Hyperglycemia

Intervention

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:
• 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

Locations

Country	Name	City	State
United States	Emory Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Number of ICU Readmissions	The number of readmissions to the ICU.	During the hospital stay (up to 12 days postoperatively)
Secondary	Number of Cerebrovascular Events	The number of cerebrovascular events.	During the hospital stay (up to 12 days postoperatively)
Secondary	Participant Mortality	The number of participant deaths while in the ICU and hospital.	During the hospital stay (up to 12 days postoperatively)