Clinical trial NCT01765270: Mechanistic Assessment of the Properties of Saxagliptin in Subjects Undergoing Coronary Artery Bypass Graft Surgery
Official title: Mechanistic Assessment of the Properties of Saxagliptin in Subjects Undergoing Coronary Artery Bypass Graft Surgery: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Cardiovascular Disease
Keywords: Diabetes
Diabetes Mellitus
Type 2 Diabetes
Cardiovascular Disease
Coronary Artery Bypass Surgery
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2013-01-10
Enrollment: 12
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.

Eligibility criteria: 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

Primary outcomes:
measure: Troponin I (TnI) Area Under the Curve (AUC)
timeFrame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days)
Secondary outcomes:
measure: High Sensitive Troponin-I (hsTnT) Area Under the Curve
timeFrame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days)
measure: Creatine Kinase-Myocardial Bands (CK-MB) Area Under the Curve
timeFrame: pre-CABG surgery (after 5 to 7 days of assigned treatment, predischarge or 5 days post-CABG surgery (Approximately 12 days)
measure: Number of Major Adverse Cardiac Events (MACE)
timeFrame: Baseline to end of study (Approximately 35-37 days)
measure: Duration of Inotropic Support
timeFrame: CABG surg until hosp discharge (Approximately 5 days)
measure: Number of Participants Who Had an Episode of Hypoglycemia
timeFrame: baseline to end of study (Approximately 35-37 days)
measure: Number of Participants Who Required Intraaortic Balloon Pump (IABP) Support
timeFrame: CABG to hospital discharge (Approximately 5 days)
measure: Need for Antiarrhythmic Therapy
timeFrame: CABG surg to hospital discharge Approximately 5 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology, PC
state: Alabama
city: Birmingham
country: United States
facility: Cardio-Thoracic Surgeons PC
state: Alabama
city: Huntsville
country: United States
facility: Heart Center Research, LLC
state: Alabama
city: Fort Smith
country: United States
facility: Sparks Regional Medical Center
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Cardiology, PA
state: Arkansas
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Richmond
country: United States
facility: Chippenham Medical Center
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center (CAMC)
state: West Virginia
Study officials:
affiliation: Duke University
name: L. Kristin Newby, M.D., MHS
role: PRINCIPAL_INVESTIGATOR
References: