Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery (CABG)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Other: Regular insulin (intensive treatment); Other: Regular Insulin (conventional treatment)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30326
      • Emory University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females between the ages of 18 and 80 years undergoing CABG +/- valve surgery.
2. Post surgical hyperglycemia (BG > 140 mg/dl).
3. Patients with and without a history of type 2 diabetes

Exclusion Criteria:

1. Patients requiring combination CABG with additional procedures such aorta replacement.
2. Patients with severely impaired renal function (serum creatinine ≥3.0 mg/dl or GFR < 30 ml/min) or clinically significant hepatic failure.
3. Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state.
4. Moribund patients and those at imminent risk of death (brain death or cardiac standstill).
5. 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.
6. Female subjects who are pregnant or breast-feeding at time of enrollment into the study.

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
Active Comparator: Intensive insulin treatment; Intensive insulin treatment (BG target: 100-140 mg/dL)	Other: Regular insulin (intensive treatment); Titration of the IV insulin rate for glucose goal 100-140 mg/dL
Active Comparator: Conventional insulin treatment; Conventional insulin treatment (BG target: 141-180 mg/dl)	Other: Regular Insulin (conventional treatment); Titration of the IV insulin rate for glucose goal 141-180 mg/dl

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: American Diabetes Association
• Investigators: Principal Investigator: Guillermo E Umpierrez, MD, Emory University

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: May 26, 2011
• First Posted (Estimate): May 27, 2011

Study Record Updates

• Last Update Posted (Estimate): December 31, 2014
• Last Update Submitted That Met QC Criteria: December 18, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Diabetes; Glycemic control; Coronary Artery Bypass Surgery; Insulin infusion
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: IRB00048356; 00048356-2010 (Other Identifier: Other)