Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Phase 3

Completed

• Conditions: Diabetes
• Interventions: Other: Regular Insulin (conventional treatment); Other: Regular insulin (intensive treatment)

• Registration Number: NCT01361594
• Lead Sponsor: Emory University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2011-02-03
• Study First Submitted QC: 2011-05-26
• Study First Posted: 2011-05-27
• Study Start: 2011-06
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2014-12
• Results First Submitted: 2014-12-18
• Results First Submitted QC: 2014-12-18
• Last Update Submitted: 2014-12-18
• Results First Posted: 2014-12-31
• Last Update Posted: 2014-12-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 338

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional insulin treatment	Regular Insulin (conventional treatment)	Conventional insulin treatment (BG target: 141-180 mg/dl)
Intensive insulin treatment	Regular insulin (intensive treatment)	Intensive insulin treatment (BG target: 100-140 mg/dL)

Primary Outcome Measures

Name	Time	Method
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.
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

Secondary Outcome Measures

Name	Time	Method
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	within 3 months after discharge	Superficial and deep sternal wound infection
Duration of Ventilatory Support and ICU Readmission	average 1 month during the hospitalization	Duration of ventilatory support and ICU readmission
Number of Hospital Readmissions and Emergency Room Visits	Within 30 days after discharge	Number of hospital readmissions and emergency room visits
Major Cardiovascular Events	within 3 months after discharge	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
Cerebrovascular Events	within 3 months after discharge	permanent stroke and reversible ischemic neurologic deficit
Measures of Inflammation	average 1 month during the hospitalization	Measures of inflammation (C-reactive protein, TNF-alpha; IL-6) and oxidative stress markers
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).
Thirty Day Mortality	within 30 days of discharge	Thirty day mortality
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
Pneumonia (CDC Criteria)	Within 3 months after discharge	Pneumonia (CDC criteria)
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

Trial Locations

Locations (1)

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States