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

Phase 4

Terminated

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Saxagliptin	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)	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)
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

Locations (10): Heart Center Research, LLC
🇺🇸
Huntsville, Alabama, United States
Arkansas Cardiology, PA
🇺🇸
Little Rock, Arkansas, United States
Stanford University Medical Center
🇺🇸
Palo Alto, California, United States
Cardiology, PC
🇺🇸
Birmingham, Alabama, United States
Sparks Regional Medical Center
🇺🇸
Fort Smith, Arkansas, United States
Emory University Hospital Midtown
🇺🇸
Atlanta, Georgia, United States
Duke University Medical Center (DUMC)
🇺🇸
Durham, North Carolina, United States
Chippenham Medical Center
🇺🇸
Richmond, Virginia, United States
Cardio-Thoracic Surgeons PC
🇺🇸
Birmingham, Alabama, United States
Charleston Area Medical Center (CAMC)
🇺🇸
Charleston, West Virginia, United States