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

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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:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
The Cleveland Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Hyperglycemia
Aortic Valve Replacement
Aortic Stenosis
Cardiac Surgery
Interventions Other: hyperinsulinemic normoglycemic clamp (HNC)
Other: control group
Enrollment 100
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Hide Arm/Group Description

Patients will be randomized to receive treatment with HNC during cardiac surgery.

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.

Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.

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.

Period Title: Overall Study
Started 50 50
Completed 49 48
Not Completed 1 2
Arm/Group Title Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management Total
Hide Arm/Group Description

Patients will be randomized to receive treatment with HNC during cardiac surgery.

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.

Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.

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.

Total of all reporting groups
Overall Number of Baseline Participants 49 48 97
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants 48 participants 97 participants
70  (9) 70  (11) 70  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 48 participants 97 participants
Female
13
  26.5%
17
  35.4%
30
  30.9%
Male
36
  73.5%
31
  64.6%
67
  69.1%
1.Primary Outcome
Title Myocardial Function: Left Ventricular Global Longitudinal Strain (%)
Hide Description

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.

Time Frame end of surgery (closure), an average of 5 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
some patient's echocardiography were low quality and can not be used
Arm/Group Title Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Hide Arm/Group Description:

Patients will be randomized to receive treatment with HNC during cardiac surgery.

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.

Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.

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.

Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: percentage of myocardial shortening
-16.8  (4.6) -15.9  (4.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic Normoglycemic Clamp (HNC), Standard Glucose Management
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.2
Confidence Interval (2-Sided) 97.5%
-2.87 to 0.48
Estimation Comments [Not Specified]
2.Primary Outcome
Title Intraoperative Left Ventricular (LV) Global Longitudinal Strain Rate
Hide Description

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

Time Frame end of surgery (closure) an average of 5 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
some patient's echocardiography were low quality and can not be used
Arm/Group Title Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Hide Arm/Group Description:

Patients will be randomized to receive treatment with HNC during cardiac surgery.

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.

Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.

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.

Overall Number of Participants Analyzed 33 34
Mean (Standard Deviation)
Unit of Measure: Percent / sec
-1.1  (0.3) -1.0  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic Normoglycemic Clamp (HNC), Standard Glucose Management
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method t-test, 2 sided
Comments paired t-test
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 97.5%
-0.3 to -0.01
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain
Hide Description

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.

Time Frame end of surgery (closure) an average of 5 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
some patient's echocardiography were low quality and can not be used
Arm/Group Title Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Hide Arm/Group Description:

Patients will be randomized to receive treatment with HNC during cardiac surgery.

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.

Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.

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.

Overall Number of Participants Analyzed 26 28
Mean (Standard Deviation)
Unit of Measure: percentage of myocardial shortening
-17.2  (4.3) -17.3  (3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic Normoglycemic Clamp (HNC), Standard Glucose Management
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-2.6 to 1.5
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain Rate
Hide Description

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

Time Frame end of surgery (closure) an average of 5 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
some patient's echocardiography were low quality and can not be used
Arm/Group Title Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Hide Arm/Group Description:

Patients will be randomized to receive treatment with HNC during cardiac surgery.

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.

Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.

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.

Overall Number of Participants Analyzed 26 28
Mean (Standard Deviation)
Unit of Measure: Percent / sec
-1.1  (0.3) -1.1  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic Normoglycemic Clamp (HNC), Standard Glucose Management
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Hide Arm/Group Description

Patients will be randomized to receive treatment with HNC during cardiac surgery.

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.

Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.

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.

All-Cause Mortality
Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Affected / at Risk (%) Affected / at Risk (%)
Total   0/49 (0.00%)   0/48 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Affected / at Risk (%) Affected / at Risk (%)
Total   0/49 (0.00%)   0/48 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Hyperinsulinemic Normoglycemic Clamp (HNC) Standard Glucose Management
Affected / at Risk (%) Affected / at Risk (%)
Total   0/49 (0.00%)   0/48 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Andra E. Duncan, M.D
Organization: Cleveland Clinic
Phone: 216-445-2372
Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01187329     History of Changes
Other Study ID Numbers: 10-526
First Submitted: August 19, 2010
First Posted: August 24, 2010
Results First Submitted: June 4, 2018
Results First Posted: August 23, 2018
Last Update Posted: November 20, 2018