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Outcomes Study of Hyperinsulinemic Glucose Control in Cardiac Surgery

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ClinicalTrials.gov Identifier: NCT00524472
Recruitment Status : Completed
First Posted : September 3, 2007
Results First Posted : October 26, 2018
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Prevention
Condition Cardiac Surgery
Interventions Other: Hyperinsulinemic-normoglycemic clamp
Other: insulin at the standard of care levels
Enrollment 1439

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Hide Arm/Group Description

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

Period Title: Overall Study
Started 709 730
Completed 709 730
Not Completed 0 0
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels Total
Hide Arm/Group Description

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

Total of all reporting groups
Overall Number of Baseline Participants 709 730 1439
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 709 participants 730 participants 1439 participants
66  (11) 66  (11) 66  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 709 participants 730 participants 1439 participants
Female
189
  26.7%
184
  25.2%
373
  25.9%
Male
520
  73.3%
546
  74.8%
1066
  74.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 709 participants 730 participants 1439 participants
Canada
457
  64.5%
464
  63.6%
921
  64.0%
United States
252
  35.5%
266
  36.4%
518
  36.0%
1.Primary Outcome
Title Any Major Morbidity/30-day Mortality
Hide Description

a composite (any versus none) of the following major postoperative complications occurring:

  1. all-cause postoperative mortality
  2. 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
  3. serious postoperative infection
  4. acute postoperative kidney injury requiring renal replacement therapy;
  5. new postoperative focal or global neurologic deficit.
Time Frame within 30 days post surgery
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Hide Arm/Group Description:

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

Overall Number of Participants Analyzed 709 730
Measure Type: Count of Participants
Unit of Measure: Participants
46
   6.5%
82
  11.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic-normoglycemic Clamp, Insulin at the Standard of Care Levels
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0043
Comments

P-values for combined sites: significant if P < 0.0085 for efficacy. Adjusted for interim analysis.

Confidence intervals adjusted for interim analysis.

Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.39 to 0.97
Estimation Comments Hyperinsulinemic-normoglycemic clamp
2.Secondary Outcome
Title Post Operative Atrial Fibrillation
Hide Description 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
Time Frame 15 - 30 days post operative
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Hide Arm/Group Description:

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

Overall Number of Participants Analyzed 709 730
Measure Type: Count of Participants
Unit of Measure: Participants
209
  29.5%
235
  32.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic-normoglycemic Clamp, Insulin at the Standard of Care Levels
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.29
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.75 to 1.13
Estimation Comments HN vs. standard
3.Secondary Outcome
Title Duration of Hospitalization
Hide Description Days from date of surgery to hospital discharge
Time Frame starting post operative day one to discharge from hospital, on an average of 8 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Hide Arm/Group Description:

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

Overall Number of Participants Analyzed 686 713
Median (95% Confidence Interval)
Unit of Measure: days
8
(6 to 12)
8
(6 to 12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic-normoglycemic Clamp, Insulin at the Standard of Care Levels
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.91 to 1.21
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of Intensive Care Stay
Hide Description Hours from date of surgery to discharge from intensive care unit
Time Frame ICU stay hours during hospital stay after surgery, on average of 25 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Hide Arm/Group Description:

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

Overall Number of Participants Analyzed 649 671
Median (95% Confidence Interval)
Unit of Measure: hours
25
(24.9 to 26.3)
27
(25.2 to 27.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic-normoglycemic Clamp, Insulin at the Standard of Care Levels
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.98 to 1.31
Estimation Comments HN vs. Standard
5.Secondary Outcome
Title All-cause Mortality
Hide Description All-cause mortality identified during one-year follow-up.
Time Frame one year post operative
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Hide Arm/Group Description:

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

Overall Number of Participants Analyzed 653 682
Measure Type: Count of Participants
Unit of Measure: Participants
32
   4.9%
22
   3.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic-normoglycemic Clamp, Insulin at the Standard of Care Levels
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
0.74 to 3.11
Estimation Comments HN vs. standard
6.Secondary Outcome
Title a Composite of Minor Postoperative Complications
Hide Description 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.
Time Frame within 30 days after surgery
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Hide Arm/Group Description:

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

Overall Number of Participants Analyzed 709 730
Measure Type: Count of Participants
Unit of Measure: Participants
200
  28.2%
237
  32.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hyperinsulinemic-normoglycemic Clamp, Insulin at the Standard of Care Levels
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.085
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.72 to 1.07
Estimation Comments HN vs. Standard
Time Frame One Year Post-opeperative follow-up for All-Cause Mortality; 1 month Post-opeperative follow-up for Serious Adverse Events and Other (Not Including Serious) Adverse Events
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Hide Arm/Group Description

Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Hyperinsulinemic-normoglycemic clamp: Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.

Group B will be administered insulin at the standard of care levels established by the participating institution.

insulin at the standard of care levels: Subjects will be administered insulin at the standard of care levels established by the participating institution.

All-Cause Mortality
Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Affected / at Risk (%) Affected / at Risk (%)
Total   32/709 (4.51%)      22/730 (3.01%)    
Show Serious Adverse Events Hide Serious Adverse Events
Hyperinsulinemic-normoglycemic Clamp Insulin at the Standard of Care Levels
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/709 (2.54%)      27/730 (3.70%)    
Surgical and medical procedures     
sae  [1]  18/709 (2.54%)  18 27/730 (3.70%)  27
Indicates events were collected by systematic assessment
[1]
Adverse Events were monitored/assessed without regard to the specific Adverse Event Term
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 Insulin at the Standard of Care Levels
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/709 (0.00%)      0/730 (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 Duncan, MD
Organization: Cleveland Clinic
Phone: 216 445-2372
Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00524472     History of Changes
Other Study ID Numbers: 07-470
First Submitted: August 31, 2007
First Posted: September 3, 2007
Results First Submitted: March 7, 2017
Results First Posted: October 26, 2018
Last Update Posted: October 26, 2018