Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients

Study Overview
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Brief Summary
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The 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
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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 the study are to examine baseline and postoperative metabolic profiles of non-diabetic CABG patients with stress hyperglycemia and to study the effect of a long-acting GLP-1 RA on the prevention of stress-hyperglycemia and modulation of metabolic stress during cardiac surgery. The Study will be conducted in 2 Parts. The First part of the study aims to provide new insights into the mechanisms underlying the metabolic and inflammatory responses to surgical stress The first part is a nested case control study.The Second part of the study will examine whether exposure to a long acting glucagon like peptide-1 receptor agonist (GLP-1 RA), dulaglutide can improve glycemic control and ameliorate the inflammatory response to acute surgical stress. This study is a randomized study with assignment to either dulaglutide or placebo two to three days prior to surgery in non-Diabetes Mellitus obese patients (BG<126 mg/dL, HbA1c <6.5%, BMI >25, age> 40 years) undergoing CABG surgery.The study ultimately wants to provide evidence to support the use of novel therapies to prevent and manage stress hyperglycemia in the inpatient setting.

Official Title
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Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients

Conditions
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Stress Hyperglycemia

Intervention / Treatment
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* Drug: Dulaglutide Injection
* Other: Saline Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between the ages of 40 and 80 years and BMI ≥25mg/kg2 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; subjects with 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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective Placebo controlled randomized study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dulaglutide Arm<br>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 | Drug: Dulaglutide Injection<br>* 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<br>* Other names: Trulicity;|
| Placebo Comparator: Placebo Arm<br>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: Saline Injection<br>* 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<br>* Other names: Sodium Chloride Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Blood Glucose levels (BG) > 140 mg/dl during post operative period between patients randomized to dulaglutide or placebo arms | Stress-hyperglycemia is defined as Blood Glucose levels >140 mg/dl and requiring insulin therapy during the postoperative period. To to determine if dulaglutide can prevent stress-hyperglycemia, number of Blood Glucose levels (BG) > 140 mg/dl during post operative period between patients randomized to dulaglutide or placebo arms are recorded and compared. Information on BG measurements both at bedside by glucose meter and by hospital laboratory will be collected. BG will be measured every 1-2 hour during continuous insulin infusion (CII) in the ICU, and before meals and at bedtime after transition to regular wards. | Up to 7 days postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean blood glucose levels in mg/dL during the Intensive Care Unit (ICU) stay post operatively between patients randomized to dulaglutide or placebo arms | To measure glucose control the mean blood glucose levels in mg/dL during the Intensive Care Unit (ICU) stay post operatively are measured between patients randomized to dulaglutide or placebo arms. Information on BG measurements both at bedside by glucose meter and by hospital laboratory will be collected. BG will be measured every 1-2 hour 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 5 days postoperatively) | 
| Mean blood glucose levels in mg/dL during the hospital stay post operatively between patients randomized to dulaglutide or placebo arms | To measure glucose control the mean blood glucose levels in mg/dL during the hospital stay post operatively are measured between patients randomized to dulaglutide or placebo arms. Information on BG measurements both at bedside by glucose meter and by hospital laboratory will be collected. BG will be measured every 1-2 hour 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 7 days postoperatively) | 
| Frequency of rescue therapy with subcutaneous insulin after transition to regular floor post operatively between patients randomized to dulaglutide or placebo arms | Patients with 2 consecutive BG >180 mg/dl, or average daily BG >180 mg/dl will be started on rescue therapy with subcutaneous basal insulin (glargine or levemir) once daily. Information on BG measurements both at bedside by glucose meter and by hospital laboratory will be collected. BG will be measured every 1-2 hour during continuous insulin infusion (CII) in the ICU, and before meals and at bedtime after transition to regular wards.The Frequency of rescue therapy with subcutaneous insulin after transition to regular floor post operatively between patients randomized to dulaglutide or placebo arms is recorded and compared | During the hospital stay (Up to 7 days postoperatively) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Bypass Surgery (CABG), Post Operative, Obesity