Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Diabetes Clinical Trial

— CABG  

Official title:

Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01361594
• Other study ID #: IRB00048356
• Secondary ID: 00048356-2010
• Status: Completed
• Phase: Phase 3
• First received: February 3, 2011
• Last updated: December 18, 2014
• Start date: June 2011
• Est. completion date: December 2013

Study information

• Verified date: December 2014
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 338
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes

Intervention

Other:
• Regular insulin (intensive treatment)
Titration of the IV insulin rate for glucose goal 100-140 mg/dL
• Regular Insulin (conventional treatment)
Titration of the IV insulin rate for glucose goal 141-180 mg/dl

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	American Diabetes Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Within 6 months of hospitalization	No
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
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.	average 1 month during the hospitalization	Yes
Secondary	ICU and Hospital Length of Stay, and ICU Readmissions	ICU and hospital length of stay, and ICU readmissions	average 1 month during the hospitalization	Yes
Secondary	Surgical Wound Infection	superficial and deep sternal wound infection	average 1 month during the hospitalization	Yes
Secondary	Pneumonia (CDC Criteria)	Pneumonia (CDC criteria)	average 1 month during the hospitalization	Yes
Secondary	Cerebrovascular Events	permanent stroke and reversible ischemic neurologic deficit.	average 1 month during the hospitalization	Yes
Secondary	Duration of Ventilatory Support and ICU Readmission	Duration of ventilatory support and ICU readmission	average 1 month during the hospitalization	Yes
Secondary	Thirty Day Mortality	Thirty day mortality	within 30 days of discharge	Yes
Secondary	Number of Hospital Readmissions and Emergency Room Visits	Number of hospital readmissions and emergency room visits	Within 30 days after discharge	Yes
Secondary	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	Yes
Secondary	Measures of Inflammation	Measures of inflammation (C-reactive protein, TNF-alpha; IL-6) and oxidative stress markers	average 1 month during the hospitalization	No
Secondary	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	Yes
Secondary	Surgical Wound Infection	Superficial and deep sternal wound infection	within 3 months after discharge	Yes
Secondary	Pneumonia (CDC Criteria)	Pneumonia (CDC criteria)	Within 3 months after discharge	Yes
Secondary	Cerebrovascular Events	permanent stroke and reversible ischemic neurologic deficit	within 3 months after discharge	Yes