Cardiac Surgery
Conditions
Keywords
Hyperinsulinemic glucose control, cardiac surgery, Outcome
Brief summary
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.
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.
Interventions
OTHERHyperinsulinemic-normoglycemic clamp
Patients will be randomized to receive the hyperinsulinemic-normoglycemic clamp titrating the blood glucose to 80-110 mg/dL.
OTHERinsulin at the standard of care levels
Subjects will be administered insulin at the standard of care levels established by the participating institution.
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Any Major Morbidity/30-day Mortality | within 30 days post surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | one year post operative | All-cause mortality identified during one-year follow-up. |
| a Composite of Minor Postoperative Complications | within 30 days after surgery | 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. |
| Post Operative Atrial Fibrillation | 15 - 30 days post operative | 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 |
| Duration of Hospitalization | starting post operative day one to discharge from hospital, on an average of 8 days | Days from date of surgery to hospital discharge |
| Duration of Intensive Care Stay | ICU stay hours during hospital stay after surgery, on average of 25 hours | Hours from date of surgery to discharge from intensive care unit |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hyperinsulinemic-normoglycemic Clamp 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. | 709 |
| Insulin at the Standard of Care Levels 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. | 730 |
| Total | 1,439 |
Baseline characteristics
| Characteristic | Insulin at the Standard of Care Levels | Total | Hyperinsulinemic-normoglycemic Clamp |
|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 11 | 66 years STANDARD_DEVIATION 11 | 66 years STANDARD_DEVIATION 11 |
| Region of Enrollment Canada | 464 Participants | 921 Participants | 457 Participants |
| Region of Enrollment United States | 266 Participants | 518 Participants | 252 Participants |
| Sex: Female, Male Female | 184 Participants | 373 Participants | 189 Participants |
| Sex: Female, Male Male | 546 Participants | 1066 Participants | 520 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 709 | 22 / 730 |
| other Total, other adverse events | 0 / 709 | 0 / 730 |
| serious Total, serious adverse events | 18 / 709 | 27 / 730 |
Outcome results
Primary
Any Major Morbidity/30-day Mortality
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperinsulinemic-normoglycemic Clamp | Any Major Morbidity/30-day Mortality | 46 Participants |
| Insulin at the Standard of Care Levels | Any Major Morbidity/30-day Mortality | 82 Participants |
p-value: 0.004395% CI: [0.39, 0.97]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: within 30 days after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperinsulinemic-normoglycemic Clamp | a Composite of Minor Postoperative Complications | 200 Participants |
| Insulin at the Standard of Care Levels | a Composite of Minor Postoperative Complications | 237 Participants |
p-value: 0.08595% CI: [0.72, 1.07]Cochran-Mantel-Haenszel
Secondary
All-cause Mortality
All-cause mortality identified during one-year follow-up.
Time frame: one year post operative
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperinsulinemic-normoglycemic Clamp | All-cause Mortality | 32 Participants |
| Insulin at the Standard of Care Levels | All-cause Mortality | 22 Participants |
p-value: 0.1295% CI: [0.74, 3.11]Cochran-Mantel-Haenszel
Secondary
Duration of Hospitalization
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hyperinsulinemic-normoglycemic Clamp | Duration of Hospitalization | 8 days |
| Insulin at the Standard of Care Levels | Duration of Hospitalization | 8 days |
p-value: 0.9995% CI: [0.91, 1.21]Regression, Cox
Secondary
Duration of Intensive Care Stay
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hyperinsulinemic-normoglycemic Clamp | Duration of Intensive Care Stay | 25 hours |
| Insulin at the Standard of Care Levels | Duration of Intensive Care Stay | 27 hours |
p-value: 0.02595% CI: [0.98, 1.31]Regression, Cox
Secondary
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
Time frame: 15 - 30 days post operative
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperinsulinemic-normoglycemic Clamp | Post Operative Atrial Fibrillation | 209 Participants |
| Insulin at the Standard of Care Levels | Post Operative Atrial Fibrillation | 235 Participants |
p-value: 0.2995% CI: [0.75, 1.13]Cochran-Mantel-Haenszel