The Effect of the Hyperinsulinemic Normoglycemic Clamp on Myocardial Function and Utilization of Glucose

• ClinicalTrials.gov Identifier: NCT01187329
• Recruitment Status: Completed
• First Posted: August 24, 2010
• Results First Posted: August 23, 2018
• Last Update Posted: November 20, 2018
• Sponsor: The Cleveland Clinic
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): The Cleveland Clinic

Study Description

Brief Summary:

The overall research plan is to test the hypothesis that intraoperative treatment of hyperinsulinemic normoglycemic clamp (HNC) in cardiac surgical patients improves myocardial function and short-term outcomes compared with standard glucose management.

Condition or disease	Intervention/treatment	Phase
Hyperglycemia; Aortic Valve Replacement; Aortic Stenosis; Cardiac Surgery	Other: hyperinsulinemic normoglycemic clamp (HNC); Other: control group	Not Applicable

Detailed Description:

Specific Aim #1:To determine whether intraoperative use of HNC affords cardioprotective benefits measured by improved echocardiographic measures of myocardial function, serum markers of cardiomyocyte injury, and hemodynamic indices measured immediately (at end of surgery) and during the short-term (initial hospitalization).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of the Hyperinsulinemic Normoglycemic Clamp on Myocardial Function and Utilization of Glucose
• Study Start Date: October 2010
• Actual Primary Completion Date: August 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: hyperinsulinemic normoglycemic clamp (HNC); Patients will be randomized to receive treatment with HNC during cardiac surgery.	Other: hyperinsulinemic normoglycemic clamp (HNC); Prior to anesthetic induction, a baseline blood glucose value will be obtained, followed by an insulin infusion of 5 mU.Kg-1.min-1. When blood glucose is <110 mg/dL, a variable continuous infusion of glucose (dextrose 20%) supplemented with potassium (40 mEq/L) and phosphate (30 mmol/L) is administered to preserve normoglycemia (80-110 mg/dL). The glucose infusion is titrated to target glucose levels by checking blood glucose every 5 - 15 min with Accu-Check (Roche Diagnostics, Switzerland) glucose monitor. At sternal closure, insulin infusion is decreased to 1 mU/Kg/min. On admission to the ICU, insulin treatment follows the ICU protocol. The dextrose infusion is slowly weaned off over 2 - 4 hrs maintaining blood glucose > 80 mg/dL. Arterial blood glucose is measured every 30 - 60 min for 2 hrs, then, as stated in ICU protocol.
Placebo Comparator: standard glucose management; Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.	Other: control group; Baseline arterial blood glucose will be obtained before anesthetic induction. Repeat measurements are performed every 30-90 min. Glucose >150 on CPB will receive insulin according to intraoperative protocol. After surgery, insulin is given according to ICU protocol. Target glucose < 180 mg/dL.; Other Names: glucose; standard of care

Outcome Measures

Primary Outcome Measures :

1. Myocardial Function: Left Ventricular Global Longitudinal Strain (%) [ Time Frame: end of surgery (closure), an average of 5 minutes ]

   Left ventricular global longitudinal strain measured by intraoperative transesophageal echocardiography at end of surgery and assessed using off-line speckle-tracking echocardiography.

   higher values (%) mean a worse outcome.

2. Intraoperative Left Ventricular (LV) Global Longitudinal Strain Rate [ Time Frame: end of surgery (closure) an average of 5 minutes ]

   Left ventricular global longitudinal strain rate measured by intraoperative transesophageal echocardiography at end of surgery and assessed using off-line speckle-tracking echocardiography.

   higher values mean a worse outcome

Secondary Outcome Measures :

1. Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain [ Time Frame: end of surgery (closure) an average of 5 minutes ]

   Right ventricular global longitudinal strain measured by intraoperative transesophageal echocardiography at end of surgery and assessed using off-line speckle-tracking echocardiography.

   higher values mean a worse outcome.

2. Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain Rate [ Time Frame: end of surgery (closure) an average of 5 minutes ]

   Right ventricular global longitudinal strain rate measured by intraoperative transesophageal echocardiography at end of surgery and assessed using off-line speckle-tracking echocardiography.

   higher values mean a worse outcome

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 84 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 40 - 84 years old, Aortic stenosis, Scheduled for Aortic valve replacement.

Exclusion Criteria:

• Poor quality echocardiographic images unsuitable for analysis
• Off -pump surgical procedure
• Anticipated deep hypothermic circulatory arrest
• Any contraindications to transesophageal echocardiogram (TEE) or other proposed intervention
• Unable to give written informed consent (non-English speaking, vulnerable patients, etc.)

Contacts and Locations

Locations

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

The Cleveland Clinic

National Institutes of Health (NIH)

Investigators

• Principal Investigator: Andra Duncan, MD; The Cleveland Clinic

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zhang K, Sheu R, Zimmerman NM, Alfirevic A, Sale S, Gillinov AM, Duncan AE. A Comparison of Global Longitudinal, Circumferential, and Radial Strain to Predict Outcomes After Cardiac Surgery. J Cardiothorac Vasc Anesth. 2019 May;33(5):1315-1322. doi: 10.1053/j.jvca.2018.10.031. Epub 2018 Oct 24.

Sonny A, Alfirevic A, Sale S, Zimmerman NM, You J, Gillinov AM, Sessler DI, Duncan AE. Reduced Left Ventricular Global Longitudinal Strain Predicts Prolonged Hospitalization: A Cohort Analysis of Patients Having Aortic Valve Replacement Surgery. Anesth Analg. 2018 May;126(5):1484-1493. doi: 10.1213/ANE.0000000000002684.

Duncan AE, Sarwar S, Kateby Kashy B, Sonny A, Sale S, Alfirevic A, Yang D, Thomas JD, Gillinov M, Sessler DI. Early Left and Right Ventricular Response to Aortic Valve Replacement. Anesth Analg. 2017 Feb;124(2):406-418. doi: 10.1213/ANE.0000000000001108.

• Responsible Party: The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT01187329
• Other Study ID Numbers: 10-526
• First Posted: August 24, 2010
• Results First Posted: August 23, 2018
• Last Update Posted: November 20, 2018
• Last Verified: October 2018

Keywords provided by The Cleveland Clinic:

Hyperglycemia; open heart surgery; bypass

Additional relevant MeSH terms:

Aortic Valve Stenosis; Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction