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

This study is currently recruiting participants.
Verified August 2012 by Emory University
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Guillermo Umpierrez, Emory University
ClinicalTrials.gov Identifier:
NCT01361594
First received: February 3, 2011
Last updated: August 6, 2012
Last verified: August 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Diabetes
 Other: Regular insulin (intensive treatment)
Other: Regular Insulin (conventional treatment)
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:
  • To determine differences between intensive and conventional glucose control on a composite of hospital mortality and perioperative complications. [ Time Frame: within 3 months of hospialization ] [ Designated as safety issue: No ]
    The primary outcome of this trial is to compare the rate of mortality and perioperative complications including sternal wound infection (deep and superficial), bacteremia, respiratory failure, pneumonia, acute renal failure, and major cardiovascular events (acute myocardial infarction, congestive heart failure, and cardiac arrhythmias in intensive glucose control group (BG goal 100-140) with that of the conventional control (BG goal141-180) . This evaluates the efficacy of different blood glucose goals in reducing mortality and perioperative complications in CABG patients.


Secondary Outcome Measures:
  • Glycemic control [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    1. Hyperglycemic events (BG > 200 mg/dL) in ICU and non-ICU
    2. Hypoglycemic events (BG < 70 mg/dl; severe hypoglycemia (BG < 40 mg/dl).

  • Major cardiovascular events [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    1. 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).
    2. Congestive heart failure
    3. Cardiac arrhythmias: malignant arrhythmia

  • Acute renal failure [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    new-onset abnormal renal function: serum creatinine > 2.0 mg/dL or an increment level > 50% from baseline

  • Respiratory failure, defined as PaO2 value < 60 mm Hg while breathing air or a PaCO2 > 50 mm Hg. [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    Respiratory failure, defined as PaO2 value < 60 mm Hg while breathing air or a PaCO2 > 50 mm Hg.

  • ICU and hospital length of stay, and ICU readmissions [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    ICU and hospital length of stay, and ICU readmissions

  • Surgical wound infection [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    superficial and deep sternal wound infection

  • Pneumonia (CDC criteria) [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    Pneumonia (CDC criteria)

  • Cerebrovascular events [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    permanent stroke and reversible ischemic neurologic deficit.

  • ICU and hospital mortality. [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    Mortality is defined as death occurring during admission, either during ICU or after transition to non-ICU admission.

  • Duration of ventilatory support and ICU readmission [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    Duration of ventilatory support and ICU readmission

  • Thirty day mortality [ Time Frame: within 30 days of discharge ] [ Designated as safety issue: Yes ]
    Thirty day mortality

  • Number of hospital readmissions and emergency room visits [ Time Frame: Within 30 days after discharge ] [ Designated as safety issue: Yes ]
    Number of hospital readmissions and emergency room visits

  • Incidence of organ failures assessed by the daily SOFA score [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: Yes ]
    Incidence of organ failures assessed by the daily SOFA score

  • Measures of inflammation [ Time Frame: average 1 month during the hospitalization ] [ Designated as safety issue: No ]
    Measures of inflammation (C-reactive protein, TNF-alpha; IL-6) and oxidative stress markers

  • Major cardiovascular events [ Time Frame: within 3 months after discharge ] [ Designated as safety issue: Yes ]
    1. 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).
    2. Congestive heart failure
    3. Cardiac arrhythmias: malignant arrhythmia

  • Surgical wound infection [ Time Frame: within 3 months after discharge ] [ Designated as safety issue: Yes ]
    Superficial and deep sternal wound infection

  • Pneumonia (CDC criteria) [ Time Frame: Within 3 months after discharge ] [ Designated as safety issue: Yes ]
    Pneumonia (CDC criteria)

  • Cerebrovascular events [ Time Frame: within 3 months after discharge ] [ Designated as safety issue: Yes ]
    permanent stroke and reversible ischemic neurologic deficit


Estimated Enrollment: 326
Study Start Date: June 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intensive insulin treatment
Intensive insulin treatment (BG target: 100-140 mg/dL, n=163)
 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, n=163)
 Other: Regular Insulin (conventional treatment)
Titration of the IV insulin rate for glucose goal 141-180 mg/dl

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females between the ages of 18 and 80 years undergoing primary, elective and isolated CABG.
  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 as valve surgery or 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01361594

Contacts
Contact: Dawn D Smiley, MD 404-778-1664 dsmiley@emory.edu
Contact: Farnoosh Farrokhi, MD farnoosh.farrokhi@emory.edu

Locations
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30326
Contact: Farnoosh Farrokhi, MD     404-778-1687        
Contact: Dawn Smiley, MD     4047781687        
Emory Midtown Hospital Recruiting
Atlanta, Georgia, United States, 30308
Contact: Farnoosh Farrokhi, MD     404-778-1687        
Grady Memorial Hospital Recruiting
Atlanta, Georgia, United States, 30303
Contact: Farnoosh Farrokhi, MD     404-778-1687        
Sponsors and Collaborators
Emory University
American Diabetes Association
Investigators
Principal Investigator: Guillermo E Umpierrez, MD Emory University
  More Information

No publications provided

Responsible Party: Guillermo Umpierrez, Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT01361594     History of Changes
Other Study ID Numbers: 00048356-2010
Study First Received: February 3, 2011
Last Updated: August 6, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Diabetes
Coronary Artery Bypass Surgery
Glycemic control
Insulin infusion

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
 Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013