Mechanistic Assessment of the Properties of Saxagliptin in Subjects Undergoing Coronary Artery Bypass Graft Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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Mechanistic Assessment of the Properties of Saxagliptin in Subjects Undergoing Coronary Artery Bypass Graft Surgery: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Conditions
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Type 2 Diabetes Mellitus, Cardiovascular Disease

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Saxagliptin<br>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. | Drug: Saxagliptin<br>* one 5-mg saxagliptin tablet daily<br>* Other names: Onglyza;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* 5mg placebo tablet daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | Death, myocardial infarction (MI), or New congestive heart failure (CHF) | Baseline to end of study (Approximately 35-37 days) | 
| Duration of Inotropic Support |  | CABG surg until hosp discharge (Approximately 5 days) | 
| Number of Participants Who Had an Episode of Hypoglycemia |  | baseline to end of study (Approximately 35-37 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Diabetes Mellitus, Type 2 Diabetes, Cardiovascular Disease, Coronary Artery Bypass Surgery