Diabetes
Conditions
Keywords
Diabetes, Coronary Artery Bypass Surgery, Glycemic control, Insulin infusion
Brief summary
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
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.
Interventions
OTHERRegular insulin (intensive treatment)
Titration of the IV insulin rate for glucose goal 100-140 mg/dL
OTHERRegular Insulin (conventional treatment)
Titration of the IV insulin rate for glucose goal 141-180 mg/dl
Sponsors
American Diabetes Association
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects That Were Diagnosed for Peri-operative Complications | Within 6 months of hospitalization | 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 |
| Hospital Mortality | average 1 month during the hospitalization | Mortality is defined as death occurring during admission, either during ICU or after transition to non-ICU admission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Renal Failure | average 1 month during the hospitalization | 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. | average 1 month during the hospitalization | 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 | average 1 month during the hospitalization | ICU and hospital length of stay, and ICU readmissions |
| Surgical Wound Infection | average 1 month during the hospitalization | superficial and deep sternal wound infection |
| Pneumonia (CDC Criteria) | average 1 month during the hospitalization | Pneumonia (CDC criteria) |
| Glycemic Control | average 1 month during the hospitalization | 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). |
| Duration of Ventilatory Support and ICU Readmission | average 1 month during the hospitalization | Duration of ventilatory support and ICU readmission |
| Thirty Day Mortality | within 30 days of discharge | Thirty day mortality |
| Number of Hospital Readmissions and Emergency Room Visits | Within 30 days after discharge | Number of hospital readmissions and emergency room visits |
| Incidence of Organ Failures Assessed by the Daily SOFA Score | average 1 month during the hospitalization | Incidence of organ failures assessed by the daily SOFA score |
| Measures of Inflammation | average 1 month during the hospitalization | Measures of inflammation (C-reactive protein, TNF-alpha; IL-6) and oxidative stress markers |
| Cerebrovascular Events | average 1 month during the hospitalization | permanent stroke and reversible ischemic neurologic deficit. |
| Major Cardiovascular Events | average 1 month during the hospitalization | 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 |
Countries
United States
Participant flow
Recruitment details
Emory University Hospital, Emory University Hospital - Midtown and Grady Hospital
Pre-assignment details
Patients undergoing coronary artery bypass surgery (CABG) that develop hyperglycemia (defined as a blood glucose \>140) intraoperatively or in an intenstive care unit (ICU) post-surgical procedure. 33 patients withdrawn prior to randomization, due to various reasons, including surgery cancellation, transportation to a different hospital, etc.
Participants by arm
| Arm | Count |
|---|---|
| Intensive Insulin Treatment Intensive insulin treatment (BG target: 100-140 mg/dL)
Regular insulin (intensive treatment): Titration of the IV insulin rate for glucose goal 100-140 mg/dL | 151 |
| Conventional Insulin Treatment Conventional insulin treatment (BG target: 141-180 mg/dl)
Regular Insulin (conventional treatment): Titration of the IV insulin rate for glucose goal 141-180 mg/dl | 151 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Intensive Insulin Treatment | Conventional Insulin Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 72 Participants | 71 Participants | 143 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 80 Participants | 159 Participants |
| Sex: Female, Male Female | 45 Participants | 39 Participants | 84 Participants |
| Sex: Female, Male Male | 106 Participants | 112 Participants | 218 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 151 | 50 / 151 |
| serious Total, serious adverse events | 63 / 151 | 78 / 151 |
Outcome results
Primary
Hospital Mortality
Mortality is defined as death occurring during admission, either during ICU or after transition to non-ICU admission.
Time frame: average 1 month during the hospitalization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Insulin Treatment | Hospital Mortality | 5 participants |
| Conventional Insulin Treatment | Hospital Mortality | 2 participants |
Primary
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
Time frame: Within 6 months of hospitalization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Insulin Treatment | Number of Subjects That Were Diagnosed for Peri-operative Complications | 58 participants |
| Conventional Insulin Treatment | Number of Subjects That Were Diagnosed for Peri-operative Complications | 70 participants |
Secondary
Acute Renal Failure
new-onset abnormal renal function: serum creatinine \> 2.0 mg/dL or an increment level \> 50% from baseline
Time frame: average 1 month during the hospitalization
Secondary
Cerebrovascular Events
permanent stroke and reversible ischemic neurologic deficit.
Time frame: average 1 month during the hospitalization
Secondary
Cerebrovascular Events
permanent stroke and reversible ischemic neurologic deficit
Time frame: within 3 months after discharge
Secondary
Duration of Ventilatory Support and ICU Readmission
Duration of ventilatory support and ICU readmission
Time frame: average 1 month during the hospitalization
Secondary
Glycemic Control
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).
Time frame: average 1 month during the hospitalization
Secondary
ICU and Hospital Length of Stay, and ICU Readmissions
ICU and hospital length of stay, and ICU readmissions
Time frame: average 1 month during the hospitalization
Secondary
Incidence of Organ Failures Assessed by the Daily SOFA Score
Incidence of organ failures assessed by the daily SOFA score
Time frame: average 1 month during the hospitalization
Secondary
Major Cardiovascular Events
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
Time frame: within 3 months after discharge
Secondary
Major Cardiovascular Events
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
Time frame: average 1 month during the hospitalization
Secondary
Measures of Inflammation
Measures of inflammation (C-reactive protein, TNF-alpha; IL-6) and oxidative stress markers
Time frame: average 1 month during the hospitalization
Secondary
Number of Hospital Readmissions and Emergency Room Visits
Number of hospital readmissions and emergency room visits
Time frame: Within 30 days after discharge
Secondary
Pneumonia (CDC Criteria)
Pneumonia (CDC criteria)
Time frame: Within 3 months after discharge
Secondary
Pneumonia (CDC Criteria)
Pneumonia (CDC criteria)
Time frame: average 1 month during the hospitalization
Secondary
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.
Time frame: average 1 month during the hospitalization
Secondary
Surgical Wound Infection
Superficial and deep sternal wound infection
Time frame: within 3 months after discharge
Secondary
Surgical Wound Infection
superficial and deep sternal wound infection
Time frame: average 1 month during the hospitalization
Secondary
Thirty Day Mortality
Thirty day mortality
Time frame: within 30 days of discharge