Clinical trial NCT01361594: Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery
Official title: Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Keywords: Diabetes
Coronary Artery Bypass Surgery
Glycemic control
Insulin infusion
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
First posted: 2011-05-27
Enrollment: 338
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects That Were Diagnosed for Peri-operative Complications
timeFrame: Within 6 months of hospitalization
measure: Hospital Mortality
timeFrame: average 1 month during the hospitalization
Secondary outcomes:
measure: Glycemic Control
timeFrame: average 1 month during the hospitalization
measure: Major Cardiovascular Events
timeFrame: average 1 month during the hospitalization
measure: Acute Renal Failure
timeFrame: average 1 month during the hospitalization
measure: Respiratory Failure, Defined as PaO2 Value < 60 mm Hg While Breathing Air or a PaCO2 > 50 mm Hg.
timeFrame: average 1 month during the hospitalization
measure: ICU and Hospital Length of Stay, and ICU Readmissions
timeFrame: average 1 month during the hospitalization
measure: Surgical Wound Infection
timeFrame: average 1 month during the hospitalization
measure: Pneumonia (CDC Criteria)
timeFrame: average 1 month during the hospitalization
measure: Cerebrovascular Events
timeFrame: average 1 month during the hospitalization
measure: Duration of Ventilatory Support and ICU Readmission
timeFrame: average 1 month during the hospitalization
measure: Thirty Day Mortality
timeFrame: within 30 days of discharge
measure: Number of Hospital Readmissions and Emergency Room Visits
timeFrame: Within 30 days after discharge
measure: Incidence of Organ Failures Assessed by the Daily SOFA Score
timeFrame: average 1 month during the hospitalization
measure: Measures of Inflammation
timeFrame: average 1 month during the hospitalization
measure: Major Cardiovascular Events
timeFrame: within 3 months after discharge
measure: Surgical Wound Infection
timeFrame: within 3 months after discharge
measure: Pneumonia (CDC Criteria)
timeFrame: Within 3 months after discharge
measure: Cerebrovascular Events
timeFrame: within 3 months after discharge
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Guillermo E Umpierrez, MD
role: PRINCIPAL_INVESTIGATOR
References: