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The purpose of this study is to compare sitagliptin and placebo for the prevention of high blood glucose during surgery.
About 80% of patients develop high glucose after cardiac surgery. High glucose is linked to an increased risk of hospital complications. High glucose increases the risk of wound infection, kidney failure and death. Patients with high glucose are treated with insulin given through an arm vein or by frequent insulin injections under the skin. This study will determine if sitagliptin can prevent the development of high glucose after heart surgery. Sitagliptin is a diabetes pill approved by the Food and Drug Administration (FDA) to treat patients with diabetes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sitagliptin | Experimental | Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take sitagliptin. Subjects with stress hyperglycemia (defined as a BG >180 mg/dL) in the intensive care unit (ICU) will continue to receive sitagliptin and will be started on continuous intravenous insulin (Regular Human Insulin) adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol. Additionally, once moved to the regular floors and out of ICU, the subjects can receive insulin glargine, insulin lispro, and/or insulin aspart depending on the blood glucose level. |
|
| Placebo | Placebo Comparator | Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take a placebo. Subjects with stress hyperglycemia (defined as a BG >180 mg/dL) in the intensive care unit (ICU) will continue to receive a placebo and will be started on continuous intravenous insulin (Regular Human Insulin) adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol. Additionally, once moved to the regular floors and out of ICU, the subjects can receive insulin glargine, insulin lispro, and/or insulin aspart depending on the blood glucose level. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sitagliptin | Drug | Subjects will take one pill daily until the day prior to them being discharged from the hospital. Sitagliptin will be dispensed orally at 100 mg/day and at a lower dose 50 mg for patients with glomerular filtration rate (GFR) < 30-50. If the calculated GFR drops to 30 mL/min/1.73m2 or below, patients will receive study medication 25mg daily |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Stress Hyperglycemic Events in the Intensive Care Unit (ICU) | Number of participants who developed stress hyperglycemia (BG >180 mg/dl) during coronary artery bypass grafting (CABG) or after CABG requiring continuous IV insulin infusion (CII) while in the ICU. | Post-Surgery (Up to 4 Days) |
| Number of Subjects With Persistent Hyperglycemia | Number of subjects with persistent hyperglycemia (2 consecutive fasting and/or premeal BG > 180 mg/dL, or with average daily BG >180 mg/dl) who require insulin glargine (rescue therapy) after discontinuation of continuous intravenous insulin (CII) | Post-Surgery (Up to 10 Days) |
| Measure | Description | Time Frame |
|---|---|---|
| Need for Continuous Intravenous Insulin (CII) for Treatment of Hyperglycemia | Number of subjects with hyperglycemia (BG >180 mg/dL) who require CII in the ICU. | Post-Surgery (Up to 4 Days) |
| Mean Daily Intensive Care Unit (ICU) Blood Glucose (BG) Concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Guillermo Umpierrez, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Grady Health System | Atlanta | Georgia | 30303 | United States | ||
| Emory University Hospital - Midtown |
Of the 68 participants consented for study participation, seven did not begin study participation after randomization. One participant was a screen failure prior to randomization. All participants that began a study intervention were included in the baseline analysis.
Participants were recruited from four academic hospitals including Emory University Hospital, Emory Midtown Hospital, Emory Saint Joseph's, and Grady Memorial Hospital in Atlanta, Georgia between January 2016 and October 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sitagliptin | Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) were randomized to take sitagliptin. |
| FG001 | Placebo | Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) were randomized to take a placebo. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The participants included in the baseline analysis were randomized to a study arm and received an intervention.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sitagliptin | Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) were randomized to take sitagliptin. |
| BG001 | Placebo | Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) were randomized to take a placebo. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Stress Hyperglycemic Events in the Intensive Care Unit (ICU) | Number of participants who developed stress hyperglycemia (BG >180 mg/dl) during coronary artery bypass grafting (CABG) or after CABG requiring continuous IV insulin infusion (CII) while in the ICU. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 4 Days) |
|
Adverse events were collected through hospital discharge (up to 30 days).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sitagliptin | Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) were randomized to take sitagliptin. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stroke | Nervous system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Guillermo Umpierrez | Emory University | 404-778-1665 | geumpie@emory.edu |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000068900 | Sitagliptin Phosphate |
| D007328 | Insulin |
| D000069036 | Insulin Glargine |
| D061268 | Insulin Lispro |
| D061267 | Insulin Aspart |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
|
| Placebo | Drug | One pill daily until discharge |
|
| Regular Human Insulin | Drug | Continuous intravenous insulin given to ICU patients with a BG > 180 mg/DL for two consecutive readings and will be started on Regular Human Insulin adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol. Intravenous insulin infusion will be continued until the patient is able to eat and/or transferred to non-ICU service. In previous studies, average length of insulin infusion in patients with stress hyperglycemia was 16.9±19 hours and the amount of IV insulin requirement was 18.6±24.3 U/day. |
|
|
| Insulin glargine | Drug | When regular insulin is discontinued, if needed, insulin glargine will be given once daily. Patients who required continuous insulin infusion at an average rate >2U/h will be transitioned to basal (to be given approx. 4 hours prior to discontinuing the insulin drip) starting at a dose 0.2 U/Kg/d. Subjects with a BG at 140-200 mg/dL will start glargine at 0.2 U/kg weight per day. And subjects with BG between 201-400 mg/dL will start glargine at 0.2 U/Kg/day The basal insulin dose will be adjusted as follow:
|
|
|
| Supplemental insulin (Insulin lispro) | Drug | Insulin lispro will be administered before meals in addition to scheduled insulin dose following the supplemental insulin scale protocol. At bedtime, half of supplemental sliding scale insulin starting at BG >240 mg/dL will be given. For the subjects receiving supplemental insulin lispro with BG levels greater than 180 mg/dL, then supplemental insulin scale is as follows:
|
|
|
| Supplemental insulin (Insulin aspart) | Drug | Insulin aspart will be administered before meals in addition to scheduled insulin dose following the supplemental insulin scale protocol. At bedtime, half of supplemental sliding scale insulin starting at BG >240 mg/dL will be given. For the subjects receiving supplemental insulin aspart with BG levels greater than 180 mg/dL, then supplemental insulin scale is as follows:
|
|
|
The blood glucose levels will be assessed throughout the day using a glucose meter. An average will be calculated. The normal BG range for someone with diabetes is 80-130 mg/dL. |
| Post-Surgery (Up to 4 Days) |
| Mean Amount of Insulin Therapy in the Intensive Care Unit (ICU) | The mean number of insulin infusions given per day (unit/day) while subjects are in the ICU. The more insulin given, the more hyperglycemic events experienced. | Post-Surgery (Up to 4 Days) |
| Duration of Continuous Intravenous Insulin (CII) | Mean number of hours on continuous intravenous insulin (CII) after ICU discharge. | Post-Intensive Care Unit (ICU) Discharge (Up to 4 Days) |
| Mean Units Subcutaneous (SQ) Insulin Required | Mean number of supplemental insulin units (lispro or aspart) administered after receiving insulin glargine (SQ insulin). | Post-Surgery (Up to 10 Days) |
| Mean Blood Glucose (BG) Concentration After Transition From Intensive Care Unit (ICU) | The blood glucose levels will be assessed throughout the day using a glucose meter after transition form the ICU. The normal BG range for someone with diabetes is 80-130 mg/dL. | Post-Surgery (Up to 4 Days) |
| Total Insulin Therapy in the Intensive Care Unit (ICU) | Total amount of insulin glargine insulin (units) administered in the ICU per day. | Post-Surgery (Up to 4 Days) |
| Number of Participants With Severe Hyperglycemic Events During Continuous Insulin Infusion (CII) | Number of participants with two consecutive blood glucose concentrations >180 mg/dL in ICU during CII. | Post-Surgery (Up to 4 Days) |
| Number of Participants With Hyperglycemia After Transition From Intensive Care Unit (ICU) | Number of participants with blood glucose (BG) >180 after transition from ICU. | Post-Surgery (Up to 10 Days) |
| Number of Participants With Hypoglycemia During Intensive Care Unit (ICU) Stay | Number of participants with blood glucose (BG) <70 during ICU stay. | Post-Surgery (Up to 4 Days) |
| Number of Participants With Hypoglycemia After Transition From Intensive Care Unit (ICU) | Number of participants with blood glucose (BG) <70 after transition from ICU. | Post-Surgery (Up to 4 Days) |
| Number of Participants With Blood Glucose Less Than 40 mg/dl | Number of participants with blood glucose (BG) <40 throughout the duration of hospitalization. | Duration of Hospitalization (Up to 30 Days) |
| Hospital Mortality Rate | The total number of subject deaths during hospital stay will be recorded. | Post-Surgery (Up to 10 Days) |
| Intensive Care Unit (ICU) Mortality Rate | The total number of subject deaths during ICU stay will be recorded. | Post-Surgery (Up to 4 Days) |
| Number of Participants With Cerebrovascular Events | Number of participants that experienced permanent stroke and reversible ischemic neurologic deficit events. | Post-Hospital Discharge (Up to 10 Days) |
| Hospital Complication Rate | The total number of all complications experienced during hospitalization. Participants may experience more than one complication during hospitalization and these will be included in the hospital complication rate. | Duration of Hospitalization (Up to 30 days) |
| Length of Stay: Intensive Care Unit (ICU) | Number of days in the ICU after coronary artery bypass graft surgery (CABG). | Post-Surgery (Up to 4 Days) |
| Length of Hospital Stay After Study Randomization | Number of days in the hospital after a participant is randomized to a study intervention. | Post-Randomization (Up to 9 days) |
| Number of Participants Re-admitted to the Hospital Due to Wound Infections | Number of subjects readmitted to the hospital within 30 days due to wound infection. | Post-Hospital Discharge (Up to 30 Days) |
| Number of Participants Re-admitted to the Hospital Not Due to Wound Infections | Number of subjects readmitted to the hospital within 30 days for all causes excluding wound infection. | Post-Hospital Discharge (Up to 30 Days) |
| Number of Participants With Emergency Room (ER) Visits | Number of subjects returning to the ER up to 30 days (all-cause) after hospital discharge. | Post-Hospital Discharge (Up to 30 Days) |
| Number of Participants With Infections Not Requiring Hospital Re-admission | Number of subjects with infections not requiring hospital re-admission within 30 days after hospital discharge. | Post-Hospital Discharge (Up to 30 Days) |
| Number of Subjects Requiring the Use of Inotropes for Greater Than 24 Hours | The number of subjects requiring the use of inotropes for >24 hours post CABG. | Post-Surgery (Up to 2 Days) |
| Number of Subjects Requiring Re-intubation | The number of subjects requiring re-intubation after CABG. | Post-Surgery (Up to 2 Days) |
| Number of Subjects Requiring Re-intubation Within 24 Hours | The number of subjects requiring re-intubation with 24 after CABG. | Post-Surgery (Up to 24 Hours) |
| Number of Subject Requiring Surgical Re-Intervention | The number of subjects that require surgical re-intervention due to mediastinal exploration and post-operative hemorrhage. | Post-Surgery (Up to 10 Days) |
| Atlanta |
| Georgia |
| 30308 |
| United States |
| Emory University Hospital | Atlanta | Georgia | 30322 | United States |
| Emory Saint Joseph's Hospital | Atlanta | Georgia | 30342 | United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Primary | Number of Subjects With Persistent Hyperglycemia | Number of subjects with persistent hyperglycemia (2 consecutive fasting and/or premeal BG > 180 mg/dL, or with average daily BG >180 mg/dl) who require insulin glargine (rescue therapy) after discontinuation of continuous intravenous insulin (CII) | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 10 Days) |
|
|
|
| Secondary | Need for Continuous Intravenous Insulin (CII) for Treatment of Hyperglycemia | Number of subjects with hyperglycemia (BG >180 mg/dL) who require CII in the ICU. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 4 Days) |
|
|
|
| Secondary | Mean Daily Intensive Care Unit (ICU) Blood Glucose (BG) Concentration | The blood glucose levels will be assessed throughout the day using a glucose meter. An average will be calculated. The normal BG range for someone with diabetes is 80-130 mg/dL. | Participants that completed all study assessments. | Posted | Mean | Standard Deviation | mg/dL | Post-Surgery (Up to 4 Days) |
|
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|
| Secondary | Mean Amount of Insulin Therapy in the Intensive Care Unit (ICU) | The mean number of insulin infusions given per day (unit/day) while subjects are in the ICU. The more insulin given, the more hyperglycemic events experienced. | Participants that completed all study assessments. | Posted | Mean | Standard Deviation | units per day | Post-Surgery (Up to 4 Days) |
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| Secondary | Duration of Continuous Intravenous Insulin (CII) | Mean number of hours on continuous intravenous insulin (CII) after ICU discharge. | Participants that completed all study assessments. | Posted | Mean | Inter-Quartile Range | hours | Post-Intensive Care Unit (ICU) Discharge (Up to 4 Days) |
|
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|
| Secondary | Mean Units Subcutaneous (SQ) Insulin Required | Mean number of supplemental insulin units (lispro or aspart) administered after receiving insulin glargine (SQ insulin). | Participants that completed all study assessments. | Posted | Mean | Standard Deviation | units | Post-Surgery (Up to 10 Days) |
|
|
|
| Secondary | Mean Blood Glucose (BG) Concentration After Transition From Intensive Care Unit (ICU) | The blood glucose levels will be assessed throughout the day using a glucose meter after transition form the ICU. The normal BG range for someone with diabetes is 80-130 mg/dL. | Participants that completed all study assessments. | Posted | Mean | Standard Deviation | mg/dl | Post-Surgery (Up to 4 Days) |
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|
| Secondary | Total Insulin Therapy in the Intensive Care Unit (ICU) | Total amount of insulin glargine insulin (units) administered in the ICU per day. | Participants that completed all study assessments. | Posted | Mean | Standard Deviation | units per day | Post-Surgery (Up to 4 Days) |
|
|
|
| Secondary | Number of Participants With Severe Hyperglycemic Events During Continuous Insulin Infusion (CII) | Number of participants with two consecutive blood glucose concentrations >180 mg/dL in ICU during CII. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 4 Days) |
|
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|
| Secondary | Number of Participants With Hyperglycemia After Transition From Intensive Care Unit (ICU) | Number of participants with blood glucose (BG) >180 after transition from ICU. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 10 Days) |
|
|
|
| Secondary | Number of Participants With Hypoglycemia During Intensive Care Unit (ICU) Stay | Number of participants with blood glucose (BG) <70 during ICU stay. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 4 Days) |
|
|
|
| Secondary | Number of Participants With Hypoglycemia After Transition From Intensive Care Unit (ICU) | Number of participants with blood glucose (BG) <70 after transition from ICU. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 4 Days) |
|
|
|
| Secondary | Number of Participants With Blood Glucose Less Than 40 mg/dl | Number of participants with blood glucose (BG) <40 throughout the duration of hospitalization. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Duration of Hospitalization (Up to 30 Days) |
|
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|
| Secondary | Hospital Mortality Rate | The total number of subject deaths during hospital stay will be recorded. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 10 Days) |
|
|
|
| Secondary | Intensive Care Unit (ICU) Mortality Rate | The total number of subject deaths during ICU stay will be recorded. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 4 Days) |
|
|
|
| Secondary | Number of Participants With Cerebrovascular Events | Number of participants that experienced permanent stroke and reversible ischemic neurologic deficit events. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Hospital Discharge (Up to 10 Days) |
|
|
|
| Secondary | Hospital Complication Rate | The total number of all complications experienced during hospitalization. Participants may experience more than one complication during hospitalization and these will be included in the hospital complication rate. | Participants that completed all study assessments. | Posted | Number | number of complications | Duration of Hospitalization (Up to 30 days) |
|
|
|
| Secondary | Length of Stay: Intensive Care Unit (ICU) | Number of days in the ICU after coronary artery bypass graft surgery (CABG). | Participants that completed all study assessments. | Posted | Mean | Inter-Quartile Range | days | Post-Surgery (Up to 4 Days) |
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|
| Secondary | Length of Hospital Stay After Study Randomization | Number of days in the hospital after a participant is randomized to a study intervention. | Participants that completed all study assessments. | Posted | Mean | Inter-Quartile Range | days | Post-Randomization (Up to 9 days) |
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| Secondary | Number of Participants Re-admitted to the Hospital Due to Wound Infections | Number of subjects readmitted to the hospital within 30 days due to wound infection. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Hospital Discharge (Up to 30 Days) |
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|
| Secondary | Number of Participants Re-admitted to the Hospital Not Due to Wound Infections | Number of subjects readmitted to the hospital within 30 days for all causes excluding wound infection. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Hospital Discharge (Up to 30 Days) |
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|
| Secondary | Number of Participants With Emergency Room (ER) Visits | Number of subjects returning to the ER up to 30 days (all-cause) after hospital discharge. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Hospital Discharge (Up to 30 Days) |
|
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|
| Secondary | Number of Participants With Infections Not Requiring Hospital Re-admission | Number of subjects with infections not requiring hospital re-admission within 30 days after hospital discharge. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Hospital Discharge (Up to 30 Days) |
|
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| Secondary | Number of Subjects Requiring the Use of Inotropes for Greater Than 24 Hours | The number of subjects requiring the use of inotropes for >24 hours post CABG. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 2 Days) |
|
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| Secondary | Number of Subjects Requiring Re-intubation | The number of subjects requiring re-intubation after CABG. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 2 Days) |
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|
| Secondary | Number of Subjects Requiring Re-intubation Within 24 Hours | The number of subjects requiring re-intubation with 24 after CABG. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 24 Hours) |
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| Secondary | Number of Subject Requiring Surgical Re-Intervention | The number of subjects that require surgical re-intervention due to mediastinal exploration and post-operative hemorrhage. | Participants that completed all study assessments. | Posted | Count of Participants | Participants | Post-Surgery (Up to 10 Days) |
|
|
|
| 0 |
| 32 |
| 9 |
| 32 |
| 22 |
| 32 |
| EG001 | Placebo | Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) were randomized to take a placebo. | 0 | 28 | 7 | 28 | 15 | 28 |
| Surgical Site Bleeding | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | Systematic Assessment |
|
| Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
|
| Ventricular Fibrillation | Cardiac disorders | Systematic Assessment |
|
| Heart Failure | Cardiac disorders | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | Systematic Assessment |
|
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| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D011719 |
| Pyrazines |
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D049528 | Insulin, Long-Acting |
| D061266 | Insulin, Short-Acting |