Coronary Graft Patency
Conditions
Keywords
aspirin, clopidogrel, coronary artery bypass graft, Plavix
Brief summary
The design of the study will be randomized, double blind trial, which will examine the effects of addition of clopidogrel to current guideline recommended background therapy on lowering the incidence of graft stenosis after coronary artery bypass grafting compared to placebo.
Detailed description
The purpose of this study is to evaluate how well the combination of clopidogrel and aspirin lower the risk of clot forming in the bypass graft after open heart surgery. This combination has not yet been approved by the Food & Drug Administration (FDA) for treating clots in the bypass graft. However, the FDA has not objected to its use to study its safety and effectiveness. This study will enroll approximately 150 total subjects all of which will be at Brooke Army Medical Center/Wilford Hall Medical Center. The study will be for 52 weeks from the day of surgery. After bypass surgery and inclusion criteria is met, subjects will be placed on aspirin 81 mg once daily and placebo once daily or aspirin 81 mg once daily and clopidogrel 75mg once daily to keep the bypass grafts open after surgery. There are no studies to date comparing the two study groups A CT scan of the heart will be done 2 weeks after surgery to see if the grafts are still open. At the end of the study, at 52-weeks mark, the subjects will undergo another heart scan to evaluate the bypass grafts and see if they are still open. Subjects will be seen on a 3 months basis until the end of the study, unless deemed necessary to return earlier for follow up. Subjects will undergo blood draw for complete blood count as part of the follow up visits to assess for safety while on the current study drug.
Interventions
DRUGclopidogrel
clopidogrel 75mg daily by mouth daily for 12 months
DRUGsugar pill
sugar pill by mouth daily for 12 months
DRUGAspirin
aspirin 81 mg daily by mouth for 12 months ( Standard of care in both arms)
Sponsors
Bristol-Myers Squibb
Ahmad Slim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients undergoing coronary artery bypass grafting, with or without cardiopulmonary bypass * Age ≥ 18
Exclusion criteria
* Left ventricle ejection fraction \<30% * Emergency surgery * Valve surgery * Redo CABG * Postoperative cardiogenic shock for more than 48 hours * Postoperative bleeding or cardiac tamponade * More than 24 hours postoperative intubation course * Requirement of postoperative anticoagulation * Serum creatinine \>1.4 * Contraindication to use of postoperative coronary CT scan * Allergy or contraindication to aspirin or clopidogrel * Inability to provide informed consent * Pregnant or breast feeding females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of More Than 50% Stenosis in Graft With Combination Therapy With Aspirin and Clopidogrel vs. Aspirin Alone | 52 weeks | Incidence of more than 50% stenosis in graft with combination therapy with aspirin and clopidogrel vs. aspirin and placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Bleeding Between the Two Treatment Arms | 52 weeks | — |
| Number of Major Adverse Cardiovascular Events With Combination Therapy | 52 weeks | Number of major adverse cardiovascular events(angina, any thrombotic events, and myocardial infarction) with combination therapy with aspirin and clopidogrel vs. aspirin alone |
| Number of Angina Events | 52 weeks | Number of angina events with combination therapy with aspirin and clopidogrel vs. aspirin alone |
| Number of Myocardial Infarction Events | 52 weeks | Number of myocardial infarction events with combination therapy with aspirin and clopidogrel vs. aspirin alone |
| Number of Thrombotic Events | 52 weeks | Number of thrombotic events with combination therapy with aspirin and clopidogrel vs. aspirin alone |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clopidogrel aspirin and clopidogrel
clopidogrel: clopidogrel 75mg daily and aspirin 81mg by mouth daily for 12 months | 12 |
| Sugar Pill aspirin and placebo
sugar pill: sugar pill and aspirin 81mg by mouth daily for 12 months | 8 |
| Total | 20 |
Baseline characteristics
| Characteristic | Clopidogrel | Sugar Pill | Total |
|---|---|---|---|
| Age, Continuous | 67.4 years STANDARD_DEVIATION 9.7 | 64.8 years STANDARD_DEVIATION 10.2 | 66.4 years STANDARD_DEVIATION 9.9 |
| Diastolic Blood Pressure | 69.5 mmHg STANDARD_DEVIATION 9.1 | 65.1 mmHg STANDARD_DEVIATION 7.3 | 67.8 mmHg STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 12 participants | 8 participants | 20 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 18 Participants |
| Systolic Blood Pressure | 117.8 mmHg STANDARD_DEVIATION 10.7 | 115.4 mmHg STANDARD_DEVIATION 12.34 | 116.8 mmHg STANDARD_DEVIATION 11.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 10 / 12 | 6 / 8 |
Outcome results
Primary
Incidence of More Than 50% Stenosis in Graft With Combination Therapy With Aspirin and Clopidogrel vs. Aspirin Alone
Incidence of more than 50% stenosis in graft with combination therapy with aspirin and clopidogrel vs. aspirin and placebo
Time frame: 52 weeks
Population: Incidence of more than 50% stenosis in graft with combination therapy with aspirin and clopidogrel vs. aspirin and placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clopidogrel | Incidence of More Than 50% Stenosis in Graft With Combination Therapy With Aspirin and Clopidogrel vs. Aspirin Alone | 10 occluded grafts |
| Sugar Pill | Incidence of More Than 50% Stenosis in Graft With Combination Therapy With Aspirin and Clopidogrel vs. Aspirin Alone | 9 occluded grafts |
Secondary
Incidence of Bleeding Between the Two Treatment Arms
Time frame: 52 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clopidogrel | Incidence of Bleeding Between the Two Treatment Arms | 0 BLEEDING EVENTS |
| Sugar Pill | Incidence of Bleeding Between the Two Treatment Arms | 0 BLEEDING EVENTS |
Secondary
Number of Angina Events
Number of angina events with combination therapy with aspirin and clopidogrel vs. aspirin alone
Time frame: 52 weeks
Population: above is the total number of participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clopidogrel | Number of Angina Events | 7 Angina Events over 52Wks |
| Sugar Pill | Number of Angina Events | 5 Angina Events over 52Wks |
Secondary
Number of Major Adverse Cardiovascular Events With Combination Therapy
Number of major adverse cardiovascular events(angina, any thrombotic events, and myocardial infarction) with combination therapy with aspirin and clopidogrel vs. aspirin alone
Time frame: 52 weeks
Population: above is the total number of all events reported
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clopidogrel | Number of Major Adverse Cardiovascular Events With Combination Therapy | 10 MACE Events over 52Wks |
| Sugar Pill | Number of Major Adverse Cardiovascular Events With Combination Therapy | 6 MACE Events over 52Wks |
Secondary
Number of Myocardial Infarction Events
Number of myocardial infarction events with combination therapy with aspirin and clopidogrel vs. aspirin alone
Time frame: 52 weeks
Population: above is the total number of participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clopidogrel | Number of Myocardial Infarction Events | 2 MI Events over 52Wks |
| Sugar Pill | Number of Myocardial Infarction Events | 1 MI Events over 52Wks |
Secondary
Number of Thrombotic Events
Number of thrombotic events with combination therapy with aspirin and clopidogrel vs. aspirin alone
Time frame: 52 weeks
Population: above is the total number of participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clopidogrel | Number of Thrombotic Events | 1 thrombotic Events over 52Wks |
| Sugar Pill | Number of Thrombotic Events | 0 thrombotic Events over 52Wks |