Outcomes Study of Hyperinsulinemic Glucose Control in Cardiac Surgery

The Effect of Hyperinsulinemic Glucose Control on Outcomes Following Cardiac Surgery

Patients undergoing cardiac surgery will be randomized into one of two groups. Group A will be administered insulin using the hyperinsulinemic-normoglycemic clamp to normalize blood glucose levels intra-operatively. Group B will be administered insulin at the standard of care levels established by the participating institution. Patients will be followed at 10 days, 15 days and one year post-operatively.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery
• Intervention / Treatment: Other: Hyperinsulinemic-normoglycemic clamp; Other: insulin at the standard of care levels

Detailed Description

Using a randomized, controlled design, we propose to test the primary hypothesis that normalization of blood glucose using a hyperinsulinemic-normoglycemic clamp technique reduces the risk of a composite outcome (one or more) of 30-day postoperative mortality and serious postoperative cardiac, renal, neurologic, and infectious postoperative complications in patients undergoing cardiac surgery.

Our secondary hypothesis is that hyperinsulinemic normoglycemic therapy will reduce length of stay in intensive care unit, atrial dysrhythmias, creatinine elevation, hospital readmission, all-cause and cardiac one-year mortality.

• Study Type: Interventional
• Enrollment (Actual): 1439
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital
• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-90 years old
• Scheduled for cardiac surgery requiring cardiopulmonary bypass

Exclusion Criteria:

• Off-pump surgical procedures
• Anticipated deep hypothermic circulatory arrest
• In available, baseline cardiac troponin I (>0.5 ng/L) or troponin T (> 0.1 ng/mL) levels (at RVH or CC, respectively)
• Any contraindications to the proposed interventions
• Active infection, including patients with endocarditis or infected pacemaker leads.
• Any infection requiring long- term antibiotics ( > 14 days)
• kidney disease requiring renal replacement therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperinsulinemic-normoglycemic clamp; Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.	Other: Hyperinsulinemic-normoglycemic clamp; Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.; Other Names: clamp; Hyperinsulinemic
Other: Insulin at the standard of care levels; Group B will be administered insulin at the standard of care levels established by the participating institution.	Other: insulin at the standard of care levels; Subjects will be administered insulin at the standard of care levels established by the participating institution.; Other Names: insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any Major Morbidity/30-day Mortality	a composite (any versus none) of the following major postoperative complications occurring: all-cause postoperative mortality; failure to wean from cardiopulmonary bypass or postoperative low cardiac index requiring mechanical circulatory support with intraaortic balloon counterpulsation, ventricular assist device, and/or extracorporeal mechanical oxygenation; serious postoperative infection; acute postoperative kidney injury requiring renal replacement therapy;; new postoperative focal or global neurologic deficit.	within 30 days post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Operative Atrial Fibrillation	Evidence suggests that maintaining intra-operative normoglycemia during cardiac surgery while providing exogenous glucose and high-dose insulin may decrease post-operative morbidity or mortality. Using a randomized, controlled design, we propose to test the primary hypothesis that normalization of blood glucose using a hyperinsulinemic-normoglycemic clamp technique reduces the risk of a composite of serious adverse outcomes in patients undergoing cardiac surgery	15 - 30 days post operative
Duration of Hospitalization	Days from date of surgery to hospital discharge	starting post operative day one to discharge from hospital, on an average of 8 days
Duration of Intensive Care Stay	Hours from date of surgery to discharge from intensive care unit	ICU stay hours during hospital stay after surgery, on average of 25 hours
All-cause Mortality	All-cause mortality identified during one-year follow-up.	one year post operative
a Composite of Minor Postoperative Complications	a composite of minor postoperative complications, which includes: a) prolonged mechanical ventilation, b) low cardiac index, c) acute kidney injury, d) prolonged hospitalization, and 3) all-cause hospital readmission within 30 days.	within 30 days after surgery

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Study Director: Daniel I Sessler, M.D., The Cleveland Clinic; Principal Investigator: Andra I Duncan, M.D., The Cleveland Clinic; Principal Investigator: Thomas Schricker, MD, Royal Victoria Hospital, Montreal, Canada; Principal Investigator: George Carvalho, MD, Royal Victoria Hospital, Montreal, Canada

Publications and helpful links

General Publications

• Albacker TB, Carvalho G, Schricker T, Lachapelle K. Myocardial protection during elective coronary artery bypass grafting using high-dose insulin therapy. Ann Thorac Surg. 2007 Dec;84(6):1920-7; discussion 1920-7. doi: 10.1016/j.athoracsur.2007.07.001.
• Duncan AE, Kateby Kashy B, Sarwar S, Singh A, Stenina-Adognravi O, Christoffersen S, Alfirevic A, Sale S, Yang D, Thomas JD, Gillinov M, Sessler DI. Hyperinsulinemic Normoglycemia Does Not Meaningfully Improve Myocardial Performance during Cardiac Surgery: A Randomized Trial. Anesthesiology. 2015 Aug;123(2):272-87. doi: 10.1097/ALN.0000000000000723.
• Schricker T, Sato H, Beaudry T, Codere T, Hatzakorzian R, Pruessner JC. Intraoperative maintenance of normoglycemia with insulin and glucose preserves verbal learning after cardiac surgery. PLoS One. 2014 Jun 18;9(6):e99661. doi: 10.1371/journal.pone.0099661. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2007
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: August 31, 2007
• First Submitted That Met QC Criteria: August 31, 2007
• First Posted (Estimate): September 3, 2007

Study Record Updates

• Last Update Posted (Actual): October 26, 2018
• Last Update Submitted That Met QC Criteria: February 7, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: cardiac surgery; Outcome; Hyperinsulinemic glucose control
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 07-470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO