Cardiovascular Disease, Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, Diabetes Mellitus, Type 2 Diabetes, Cardiovascular Disease, Coronary Artery Bypass Surgery
Brief summary
Individuals with type 2 diabetes mellitus (T2DM) are at increased risk for cardiovascular events (for example, heart attack) and the risk is related to one's overall control of blood glucose levels. In this study the investigators will measure the effects of saxagliptin, compared to placebo, before, during, and after coronary artery bypass graft (CABG) surgery. The investigators will use samples of the patients' blood and tissue to measure and evaluate indicators of the body's response to the treatment. This study is being done to evaluate the effect of saxagliptin on biomarkers of the heart to help us understand whether reducing or controlling a person's blood glucose levels during and after CABG surgery will produce better clinical outcomes (for example, better heart health).
Detailed description
This study is a randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of saxagliptin on cardiac biomarkers of myocardial necrosis, cardiac function, inflammation, and apoptosis in subjects with Type 2 diabetes mellitus (T2DM) undergoing CABG surgery (on pump, via a median sternotomy approach) as an integrated measure of the potential mechanistic effects of saxagliptin on prevention of cardiovascular (CV) outcomes. Approximately 74 subjects will be randomized and complete the study.
Interventions
DRUGPlacebo
5mg placebo tablet daily
DRUGSaxagliptin
one 5-mg saxagliptin tablet daily
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Known diagnosis of type 2 diabetes mellitus (T2DM) with glycosylated hemoglobin (HbA1c) between 6.5% and 10%, inclusive. * Stable doses of oral antihyperglycemic agents for at least 2 months * Stable dose of chronic insulin therapy for at least 2 months * HbA1c documented within 3 months before study enrollment * Planned first elective coronary artery bypass graft (CABG) surgery
Exclusion criteria
* Elevated Creatine Kinase-Myocardial Bands (CK-MB) or troponin level above the 99th percentile at screening * Receiving incretin therapy or having received incretin therapy within the previous 2 months * Type 1 DM or a history of ketoacidosis * Women who are pregnant or breastfeeding * Known end-stage Kidney disease * Known sensitivity or intolerance to saxagliptin or dipeptidyl peptidase-4 (DPP-4) inhibitor * Clinically apparent liver disease * History of pancreatitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Troponin I (TnI) Area Under the Curve (AUC) | pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Creatine Kinase-Myocardial Bands (CK-MB) Area Under the Curve | pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days) | — |
| Number of Major Adverse Cardiac Events (MACE) | Baseline to end of study (Approximately 35-37 days) | Death, myocardial infarction (MI), or New congestive heart failure (CHF) |
| Duration of Inotropic Support | CABG surg until hosp discharge (Approximately 5 days) | — |
| High Sensitive Troponin-I (hsTnT) Area Under the Curve | pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days) | — |
| Number of Participants Who Required Intraaortic Balloon Pump (IABP) Support | CABG to hospital discharge (Approximately 5 days) | — |
| Need for Antiarrhythmic Therapy | CABG surg to hospital discharge Approximately 5 days | — |
| Number of Participants Who Had an Episode of Hypoglycemia | baseline to end of study (Approximately 35-37 days) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saxagliptin Treatments to be administered are saxagliptin 5 mg (once daily) to begin at randomization 5 to 7 days before CABG surgery, continuing through the peri-CABG surgery period and discharge, and for a total of 30 (± 5) days post-CABG surgery. | 4 |
| Placebo Treatments to be administered are placebo 5 mg (once daily) to begin at randomization 5 to 7 days before CABG surgery, continuing through the peri-CABG surgery period and discharge, and for a total of 30 (± 5) days post-CABG surgery. | 6 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Saxagliptin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 5.3 | 59.2 years STANDARD_DEVIATION 6.9 | 60.2 years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 9 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 7 Participants | 5 Participants |
| Region of Enrollment United States | 4 participants | 10 participants | 6 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 4 | 2 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 |
Outcome results
Primary
Troponin I (TnI) Area Under the Curve (AUC)
Time frame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Saxagliptin | Troponin I (TnI) Area Under the Curve (AUC) | 463.25 ng*hr/mL |
| Placebo | Troponin I (TnI) Area Under the Curve (AUC) | 235.98 ng*hr/mL |
Secondary
Creatine Kinase-Myocardial Bands (CK-MB) Area Under the Curve
Time frame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Saxagliptin | Creatine Kinase-Myocardial Bands (CK-MB) Area Under the Curve | 1174.9 ng*hr/mL |
| Placebo | Creatine Kinase-Myocardial Bands (CK-MB) Area Under the Curve | 835.76 ng*hr/mL |
Secondary
Duration of Inotropic Support
Time frame: CABG surg until hosp discharge (Approximately 5 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin | Duration of Inotropic Support | 25.67 hours | Standard Deviation 23.58 |
| Placebo | Duration of Inotropic Support | 8.49 hours | Standard Deviation 7.6 |
Secondary
High Sensitive Troponin-I (hsTnT) Area Under the Curve
Time frame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Saxagliptin | High Sensitive Troponin-I (hsTnT) Area Under the Curve | 213.82 ng*hr/mL |
| Placebo | High Sensitive Troponin-I (hsTnT) Area Under the Curve | 129.14 ng*hr/mL |
Secondary
Need for Antiarrhythmic Therapy
Time frame: CABG surg to hospital discharge Approximately 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Need for Antiarrhythmic Therapy | 4 participants |
| Placebo | Need for Antiarrhythmic Therapy | 4 participants |
Secondary
Number of Major Adverse Cardiac Events (MACE)
Death, myocardial infarction (MI), or New congestive heart failure (CHF)
Time frame: Baseline to end of study (Approximately 35-37 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Number of Major Adverse Cardiac Events (MACE) | 0 Cardiac Events |
| Placebo | Number of Major Adverse Cardiac Events (MACE) | 0 Cardiac Events |
Secondary
Number of Participants Who Had an Episode of Hypoglycemia
Time frame: baseline to end of study (Approximately 35-37 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Number of Participants Who Had an Episode of Hypoglycemia | 0 participants |
| Placebo | Number of Participants Who Had an Episode of Hypoglycemia | 0 participants |
Secondary
Number of Participants Who Required Intraaortic Balloon Pump (IABP) Support
Time frame: CABG to hospital discharge (Approximately 5 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Number of Participants Who Required Intraaortic Balloon Pump (IABP) Support | 0 participants |
| Placebo | Number of Participants Who Required Intraaortic Balloon Pump (IABP) Support | 0 participants |