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

• Sponsor: Duke University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01765270
• Collaborator: (none)
• Enrollment: 12
• Locations: 10
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus; Cardiovascular Disease	Drug: Saxagliptin; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• 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 Start Date: Mar 1, 2013
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Saxagliptin; one 5-mg saxagliptin tablet daily; Other Names: Onglyza
Placebo Comparator: 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.	Drug: Placebo; 5mg placebo tablet daily

Outcome Measures

Primary Outcome Measures

1. 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

1. 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)]

2. 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)]

3. 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)

4. Duration of Inotropic Support [CABG surg until hosp discharge (Approximately 5 days)]

5. Number of Participants Who Had an Episode of Hypoglycemia [baseline to end of study (Approximately 35-37 days)]

6. Number of Participants Who Required Intraaortic Balloon Pump (IABP) Support [CABG to hospital discharge (Approximately 5 days)]

7. Need for Antiarrhythmic Therapy [CABG surg to hospital discharge Approximately 5 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology, PC	Birmingham	Alabama	United States	35211
2	Cardio-Thoracic Surgeons PC	Birmingham	Alabama	United States	35243
3	Heart Center Research, LLC	Huntsville	Alabama	United States	35801
4	Sparks Regional Medical Center	Fort Smith	Arkansas	United States	72901
5	Arkansas Cardiology, PA	Little Rock	Arkansas	United States	72205
6	Stanford University Medical Center	Palo Alto	California	United States	94304
7	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
8	Duke University Medical Center (DUMC)	Durham	North Carolina	United States	27710
9	Chippenham Medical Center	Richmond	Virginia	United States	23225
10	Charleston Area Medical Center (CAMC)	Charleston	West Virginia	United States	25304

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: L. Kristin Newby, M.D., MHS, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01765270
• Other Study ID Numbers: Pro00041744
• First Posted: Jan 10, 2013
• Last Update Posted: May 29, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Duke University: Diabetes; Diabetes Mellitus; Type 2 Diabetes; Cardiovascular Disease; Coronary Artery Bypass Surgery
• Additional relevant MeSH terms: Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Saxagliptin

Study Results

Participant Flow

Arm/Group Title	Saxagliptin	Placebo
Arm/Group Description	Treatments to be administered are saxagliptin 5 mg (once daily) to begin at randomization 5 to 7 days before coronary artery bypass graft (CABG) surgery, continuing through the peri-CABG surgery period and discharge, and for a total of 30 (± 5) days post-CABG surgery.	Treatments to be administered are placebo 5 mg (once daily) to begin at randomization 5 to 7 days before coronary artery bypass graft (CABG) surgery, continuing through the peri-CABG surgery period and discharge, and for a total of 30 (± 5) days post-CABG surgery.
Period Title: Overall Study
STARTED	5	7
COMPLETED	4	6
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Saxagliptin	Placebo	Total
Arm/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.	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.	Total of all reporting groups
Overall Participants	4	6	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.9 (5.3)	60.2 (8.1)	59.2 (6.9)
Sex: Female, Male (Count of Participants)
Female	1 25%	1 16.7%	2 20%
Male	3 75%	5 83.3%	8 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 25%	0 0%	1 10%
Not Hispanic or Latino	3 75%	6 100%	9 90%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 50%	1 16.7%	3 30%
White	2 50%	5 83.3%	7 70%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	6 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin	Placebo
Arm/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.	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.
Measure Participants	4	6
Median (Inter-Quartile Range) [ng*hr/mL]	463.25	235.98

2. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin	Placebo
Arm/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.	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.
Measure Participants	4	6
Median (Inter-Quartile Range) [ng*hr/mL]	213.82	129.14

3. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin	Placebo
Arm/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.	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.
Measure Participants	4	6
Median (Inter-Quartile Range) [ng*hr/mL]	1174.9	835.76

4. Secondary Outcome

Title	Number of Major Adverse Cardiac Events (MACE)
Description	Death, myocardial infarction (MI), or New congestive heart failure (CHF)
Time Frame	Baseline to end of study (Approximately 35-37 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin	Placebo
Arm/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.	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.
Measure Participants	4	6
Number [Cardiac Events]	0	0

5. Secondary Outcome

Title	Duration of Inotropic Support
Time Frame	CABG surg until hosp discharge (Approximately 5 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin	Placebo
Arm/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.	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.
Measure Participants	4	6
Mean (Standard Deviation) [hours]	25.67 (23.58)	8.49 (7.60)

6. Secondary Outcome

Title	Number of Participants Who Had an Episode of Hypoglycemia
Time Frame	baseline to end of study (Approximately 35-37 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin	Placebo
Arm/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.	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.
Measure Participants	4	6
Number [participants]	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants Who Required Intraaortic Balloon Pump (IABP) Support
Time Frame	CABG to hospital discharge (Approximately 5 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin	Placebo
Arm/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.daily	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.
Measure Participants	4	6
Number [participants]	0 0%	0 0%

8. Secondary Outcome

Title	Need for Antiarrhythmic Therapy
Time Frame	CABG surg to hospital discharge Approximately 5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin	Placebo
Arm/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.	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.
Measure Participants	4	6
Number [participants]	4 100%	4 66.7%

Adverse Events

Time Frame	Participants were followed for aproximately 35 days (5 days before CABG and typically 30 days after CABG).
Arm/Group Title	Saxagliptin		Placebo
Arm/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.		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.
All Cause Mortality
	Saxagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Saxagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Saxagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		2/6 (33.3%)
Cardiac disorders
atrial fibrillation	1/4 (25%)		1/6 (16.7%)
Injury, poisoning and procedural complications
Pulmonary embolism	0/4 (0%)		1/6 (16.7%)

Limitations/Caveats

Early termination leading to small numbers of subject analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.