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

Duke University

Status and phase: Terminated; Phase 4

Conditions: Type 2 Diabetes Mellitus; Cardiovascular Disease

Treatments: Drug: Saxagliptin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01765270

Pro00041744

Details and patient eligibility

About

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).

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 45 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

12 participants in 2 patient groups, including a placebo group

Saxagliptin

Active Comparator group

Description:

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.

Treatment:

Drug: Saxagliptin

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo