Coronary Artery Disease
Conditions
Keywords
percutaneous coronary intervention, dual antiplatelet therapy, oral anticoagulant
Brief summary
Clopidogrel is the P2Y12 inhibitor of choice in PCI patients requiring OAC. However, concerns have been raised based on the notion that a considerable number of patients may have inadequate response to clopidogrel. Although practice recommendations indicate that the use of potent P2Y12 inhibitors (i.e., ticagrelor) may be considered in patients at increased thrombotic risk, they do not recommend routine testing to identify patients with poor response to clopidogrel. The aim of this study is to assess the pharmacodynamic effects of different P2Y12 inhibiting therapy (clopidogrel vs ticagrelor) in patients at high risk for high platelet reactivity identified according to the ABCD-GENE score in PCI treated patients also requiring OAC. Up to a total of up to 63 patients are planned to be prospectively enrolled in this investigation which will entail a series of comprehensive pharmacodynamic assessments to reach the study aim.
Detailed description
The combination of aspirin plus a P2Y12 receptor inhibitor, also known as dual antiplatelet therapy (DAPT), is the cornerstone of treatment for patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, a considerable number of patients undergoing PCI also have an indication to be on treatment with an oral anticoagulant (OAC). It is estimated that 10-15% of PCI patients also have an indication to be on OAC, raising concerns on their optimal antithrombotic treatment regimen. Studies have consistently shown dropping aspirin and maintaining a P2Y12 inhibitor and OAC to be associated with reduces bleeding without any significant increase in ischemic events. Accordingly, current practice recommendations is to limit the use of aspirin to the peri-PCI period and maintain dual therapy with a P2Y12 inhibitor and an OAC. Clopidogrel is the P2Y12 inhibitor of choice in PCI patients requiring OAC. However, concerns have been raised based on the notion that a considerable number of patients may have inadequate response to clopidogrel, also known as high platelet reactivity (HPR) status, and thus be at risk for thrombotic complications. Although practice recommendations indicate that the use of potent P2Y12 inhibitors (i.e., ticagrelor) may be considered in patients at increased thrombotic risk, they do not recommend routine testing to identify patients with HPR status. Nevertheless, consensus recommendations do indicate that the selective use of tests to define HPR status is a reasonable option in selected cases such as PCI patients requiring OAC. The aim of this study is to assess the pharmacodynamic effects of different P2Y12 inhibiting therapy (clopidogrel vs ticagrelor) in patients at high risk for HPR identified according to the ABCD-GENE score in PCI treated patients also requiring OAC. Up to a total of up to 63 patients are planned to be prospectively enrolled in this investigation which will entail a series of comprehensive pharmacodynamic assessments to reach the study aim.
Interventions
DRUGTicagrelor 60mg
Patients will be administered a 180 mg loading dose followed by a 60 mg bid for the duration of the study.
DRUGClopidogrel
Patients will be administered a 600 mg loading dose followed by a 75 mg daily for the duration of the study.
Sponsors
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Willing and able to provide written informed consent * Undergone successful PCI and treated with DAPT (aspirin plus a P2Y12 inhibitor) per standard of care * On treatment with a novel oral anticoagulant (apixaban, dabigatran, edoxaban, or rivaroxaban) for any indication (dosing regimen will be according to standard of care and at the discretion of the treating physician)
Exclusion criteria
* Any active bleeding or history of major bleeding * Ischemic Stroke within 1 month * Any history of hemorrhagic stroke, or intracranial hemorrhage * Known non-cardiovascular disease that is associated with poor prognosis (e.g., metastatic cancer) or that increases the risk of an adverse reaction to study interventions. * End-stage renal disease on hemodialysis * Known severe liver dysfunction or any known hepatic disease associated with coagulopathy * History of hypersensitivity or known contraindication to clopidogrel or ticagrelor. * Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein (e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus \[HIV\]-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine * Subjects who are pregnant, breastfeeding, or are of childbearing potential, and sexually active and not practicing an effective method of birth control (e.g. surgically sterile, prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, male partner sterilization) * Concomitant participation in another study with investigational drug * Hemoglobin ≤9 mg/dL * Platelet count \<80x106/mL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Reactivity Measured as PRU | 30 days | The primary end point of our study will be levels of platelet reactivity, measured as P2Y12 reaction units (PRU) using the VerifyNow system of ticagrelor versus clopidogrel in patients with an ABCD-Gene score ≥10. A PRU \>208 suggests high platelet reactivity, while \<85 may indicate increased bleeding risk. |
Countries
United States
Participant flow
Pre-assignment details
There were no wash out or run-in periods.
Participants by arm
| Arm | Count |
|---|---|
| ABCD-GENE >10 - Clopidogrel Patients with an ABCD-GENE\>10 score will be randomized in a 1:1 fashion to ticagrelor (60 mg/bid) or clopidogrel (75 mg/qd). Treatment will be maintained for 30 days. | 20 |
| ABCD-GENE >10 - Ticagrelor Patients with an ABCD-GENE\>10 score will be randomized in a 1:1 fashion to ticagrelor (60 mg/bid) or clopidogrel (75 mg/qd). Treatment will be maintained for 30 days. | 19 |
| ABCD-GENE <10 - Clopidogrel Patients with an ABCD-GENE\<10 will be treated with clopidogrel (75 mg/qd) for 30 days. | 42 |
| Total | 81 |
Baseline characteristics
| Characteristic | ABCD-GENE >10 - Ticagrelor | Total | ABCD-GENE >10 - Clopidogrel | ABCD-GENE <10 - Clopidogrel |
|---|---|---|---|---|
| Age, Continuous | 74.2 years STANDARD_DEVIATION 10.2 | 72 years STANDARD_DEVIATION 8.8 | 74.1 years STANDARD_DEVIATION 8.6 | 70.1 years STANDARD_DEVIATION 7.7 |
| PCI indication Non-ST-Segment Elevation Myocardial Infarction | 4 Participants | 14 Participants | 3 Participants | 7 Participants |
| PCI indication Stable Ischemic Heart Disease | 9 Participants | 46 Participants | 13 Participants | 24 Participants |
| PCI indication ST-elevation myocardial infarction | 3 Participants | 7 Participants | 0 Participants | 4 Participants |
| PCI indication Unstable angina | 3 Participants | 14 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 10 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 68 Participants | 15 Participants | 39 Participants |
| Sex: Female, Male Female | 8 Participants | 21 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 11 Participants | 60 Participants | 12 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 42 |
| other Total, other adverse events | 0 / 20 | 7 / 20 | 0 / 42 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 | 0 / 42 |
Outcome results
Primary
Platelet Reactivity Measured as PRU
The primary end point of our study will be levels of platelet reactivity, measured as P2Y12 reaction units (PRU) using the VerifyNow system of ticagrelor versus clopidogrel in patients with an ABCD-Gene score ≥10. A PRU \>208 suggests high platelet reactivity, while \<85 may indicate increased bleeding risk.
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABCD-GENE >10 - Clopidogrel | Platelet Reactivity Measured as PRU | 154.5 PRU |
| ABCD-GENE >10 - Ticagrelor | Platelet Reactivity Measured as PRU | 23 PRU |
| ABCD-GENE <10 - Clopidogrel | Platelet Reactivity Measured as PRU | 104 PRU |