Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Study Overview
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Brief Summary
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High blood glucose levels (hyperglycemia) in cardiac surgery patients with diabetes are associated with increased risk of hospital complications. Blood sugar control with intravenous insulin may prevent such hospital complications. Many patients undergoing cardiac bypass surgery (CABG) develop high blood sugars and require insulin therapy (shortly before or after surgery). It is not clear what the best insulin regimen is or what is the best blood sugar target in these patients. Accordingly, this research study aims to determine optimal blood glucose levels during the in patients undergoing cardiac bypass surgery. Patients will be divided in two groups. The intensive insulin group will be maintained at blood glucose between 100-140 mg/dl and the conventional treatment group at a glucose level between 140-180 mg/dl. The insulins to be used in this trial (lantus, aspart and regular insulin) are approved for use in the treatment of patients with diabetes by the FDA (Food and Drug Administration). A total of 326 patients with high blood glucose after cardiac bypass surgery will be recruited in this study. Patients will be recruited at Emory University Hospital, Emory Midtown Hospital and Grady Memorial Hospital.

Detailed Description
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Several prospective cohort studies as well as randomized clinical trials (RCT) in cardiac surgery patients have shown that intensified insulin therapy (target BG: 110-140 mg/dl) results in a reduction in short- and long-term mortality compared with conventionally treated patients. The results of recent international trials in critically ill patients; however, have failed to show a significant improvement in mortality or have even shown increased mortality risk as well as increased number of hypoglycemic events with intensive compared to less intensive glycemic control. Based on the results of these ICU trials, new ADA and AACE guidelines recommended a glycemic target between 140 and 180 mg/dl in the ICU including cardiac surgery patients. There is concern that such high BG targets might increase the risk of hospital complications in cardiac surgical patients in whom intensive glucose control has consistently reduced infections, length of hospital stay, resource utilization, and cardiac-related mortality. The overall objective of this proposal is to conduct the first prospective RCT to determine the optimal BG target during the perioperative period in hyperglycemic subjects who undergo CABG in the United States. Subjects will be randomized to undergo intensive insulin therapy adjusted to maintain a BG between 100 mg/dl and 140 mg/dl or to a conventional glucose control with a target BG between 141 mg/dl and 200 mg/dl in the ICU. The central hypothesis of this proposal is that intensive insulin management will reduce perioperative complications compared to a conventional BG control in cardiac surgery patients.

Official Title
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Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Conditions
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Diabetes

Intervention / Treatment
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* Other: Regular insulin (intensive treatment)
* Other: Regular Insulin (conventional treatment)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between the ages of 18 and 80 years undergoing CABG +/- valve surgery. Post surgical hyperglycemia (BG > 140 mg/dl). Patients with and without a history of type 2 diabetes Exclusion Criteria: Patients requiring combination CABG with additional procedures such aorta replacement. Patients with severely impaired renal function (serum creatinine ≥3.0 mg/dl or GFR < 30 ml/min) or clinically significant hepatic failure. Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state. Moribund patients and those at imminent risk of death (brain death or cardiac standstill). Patients or next-to-kin with mental condition rendering the subject or family member unable to understand the nature, scope, and possible consequences of the study. Female subjects who are pregnant or breast-feeding at time of enrollment into the study.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intensive insulin treatment<br>Intensive insulin treatment (BG target: 100-140 mg/dL) | Other: Regular insulin (intensive treatment)<br>* Titration of the IV insulin rate for glucose goal 100-140 mg/dL<br>|
| Active Comparator: Conventional insulin treatment<br>Conventional insulin treatment (BG target: 141-180 mg/dl) | Other: Regular Insulin (conventional treatment)<br>* Titration of the IV insulin rate for glucose goal 141-180 mg/dl<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects That Were Diagnosed for Peri-operative Complications | Number of participants that presented at least 1 complications including sternal wound infection, bacteremia, acute renal failure, respiratory failure, and major cardiovascular events (MACE) during the current hospitalization and up to 6 months after hospitalization | Within 6 months of hospitalization | 
| Hospital Mortality | Mortality is defined as death occurring during admission, either during ICU or after transition to non-ICU admission. | average 1 month during the hospitalization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Control | Hyperglycemic events (BG > 200 mg/dL) in ICU and non-ICU Hypoglycemic events (BG < 70 mg/dl; severe hypoglycemia (BG < 40 mg/dl). | average 1 month during the hospitalization | 
| Major Cardiovascular Events | Acute myocardial infarction : (1) typical increase and gradual decrease (troponin) or (2) more rapid increase and decrease (creatine kinase MB) of biochemical markers of myocardial necrosis with at least one of the following: (a) ischemic symptoms, (b) development of pathologic Q waves on the electrocardiogram, (c) electrocardiographic changes indicative of ischemia (ST-segment elevation or depression), or (d) coronary artery intervention (e.g., coronary angioplasty). Congestive heart failure Cardiac arrhythmias: malignant arrhythmia | average 1 month during the hospitalization | 
| Acute Renal Failure | new-onset abnormal renal function: serum creatinine > 2.0 mg/dL or an increment level > 50% from baseline | average 1 month during the hospitalization | 
| Respiratory Failure, Defined as PaO2 Value < 60 mm Hg While Breathing Air or a PaCO2 > 50 mm Hg. | Respiratory failure, defined as PaO2 value < 60 mm Hg while breathing air or a PaCO2 > 50 mm Hg. | average 1 month during the hospitalization | 
| ICU and Hospital Length of Stay, and ICU Readmissions | ICU and hospital length of stay, and ICU readmissions | average 1 month during the hospitalization | 
| Surgical Wound Infection | superficial and deep sternal wound infection | average 1 month during the hospitalization | 
| Pneumonia (CDC Criteria) | Pneumonia (CDC criteria) | average 1 month during the hospitalization | 
| Cerebrovascular Events | permanent stroke and reversible ischemic neurologic deficit. | average 1 month during the hospitalization | 
| Duration of Ventilatory Support and ICU Readmission | Duration of ventilatory support and ICU readmission | average 1 month during the hospitalization | 
| Thirty Day Mortality | Thirty day mortality | within 30 days of discharge | 
| Number of Hospital Readmissions and Emergency Room Visits | Number of hospital readmissions and emergency room visits | Within 30 days after discharge | 
| Incidence of Organ Failures Assessed by the Daily SOFA Score | Incidence of organ failures assessed by the daily SOFA score | average 1 month during the hospitalization | 
| Measures of Inflammation | Measures of inflammation (C-reactive protein, TNF-alpha; IL-6) and oxidative stress markers | average 1 month during the hospitalization | 
| Major Cardiovascular Events | Acute myocardial infarction : (1) typical increase and gradual decrease (troponin) or (2) more rapid increase and decrease (creatine kinase MB) of biochemical markers of myocardial necrosis with at least one of the following: (a) ischemic symptoms, (b) development of pathologic Q waves on the electrocardiogram, (c) electrocardiographic changes indicative of ischemia (ST-segment elevation or depression), or (d) coronary artery intervention (e.g., coronary angioplasty). Congestive heart failure Cardiac arrhythmias: malignant arrhythmia | within 3 months after discharge | 
| Surgical Wound Infection | Superficial and deep sternal wound infection | within 3 months after discharge | 
| Pneumonia (CDC Criteria) | Pneumonia (CDC criteria) | Within 3 months after discharge | 
| Cerebrovascular Events | permanent stroke and reversible ischemic neurologic deficit | within 3 months after discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Coronary Artery Bypass Surgery, Glycemic control, Insulin infusion