Coronary Artery Disease
Conditions
Keywords
dual antiplatelet therapy, rivaroxaban, pharmacodynamic
Brief summary
Recent studies indicate that anti-factor-Xa inhibition with low-dose rivaroxaban may have a role in the reduction of ischemic recurrences in patients with atherosclerotic disease manifestations. The objectives of this investigation are to assess the feasibility of switching from a DAPT to DPI regimen and to compare the pharmacodynamic profiles of these treatment regimens. This will be a prospective study conducted in cohorts of patients with CAD on treatment per standard of care with DAPT. Patients will be randomized to either maintain DAPT or to DPI. DPI consists in treatment with aspirin (81mg/qd) plus rivaroxaban (2.5mg/bid).
Detailed description
Recent studies indicate that anti-factor-Xa inhibition with low-dose rivaroxaban may have a role in the reduction of ischemic recurrences in patients with atherosclerotic disease manifestations. In the COMPASS trial, patients with stable coronary or peripheral artery disease and no indication for oral anticoagulation or dual antiplatelet therapy (DAPT) were randomized to rivaroxaban 2.5 mg bid in combination with aspirin, rivaroxaban 5 mg bid monotherapy or aspirin monotherapy. The study showed a significant 24% relative reduction in ischemic outcomes with rivaroxaban 2.5 mg bid plus aspirin combination strategy compared with aspirin alone. These observations have raised practical considerations on how to implement the results of the COMPASS trial in clinical practice particularly for patients who are completing a minimum duration of DAPT and contemplating between continuing with a DAPT regimen versus switching to a dual pathway inhibition (DPI) regimen with aspirin plus rivaroxaban. Therefore, the objectives of this investigation are to assess the feasibility of switching from a DAPT to DPI regimen and to compare the pharmacodynamic profiles of these treatment regimens. This will be a prospective study conducted in cohorts of patients with CAD on treatment per standard of care with DAPT. Patients will be randomized to either maintain DAPT or to DPI. DPI consists in treatment with aspirin (81mg/qd) plus rivaroxaban (2.5mg/bid).
Interventions
DRUGClopidogrel
Patients on aspirin and plavix will be randomized to either continue with aspirin and plavix or to switch to aspirin and rivaroxaban
DRUGPrasugrel
Patients on aspirin and prasugrel will be randomized to either continue with aspirin and prasugrel or to switch to aspirin and rivaroxaban
DRUGticagrelor
Patients on aspirin and ticagrelor will be randomized to either continue with aspirin and ticagrelor or to switch to aspirin and rivaroxaban
DRUGaspirin
all patients will remain on aspirin
DRUGrivaroxaban
Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban
Sponsors
Janssen, LP
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
laboratory personnel running pharmacodynamic testing will be blinded to treatment assignment.
Intervention model description
Patients treated with either aspirin (81mg/qd) plus clopidogrel, aspirin (81mg/qd) plus ticagrelor (90mg/bid), or aspirin (81mg/qd) plus prasugrel (10mg/bid) will be identified. Each cohort will be randomized 1:1 to either maintain DAPT or to DPI. DPI consists in treatment with aspirin (81mg/qd) plus rivaroxaban (2.5mg/bid). Patients randomized to DAPT will continue their guideline recommended DAPT regimens.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide written informed consent * Above 18 years of age * Have known CAD and have completed their required duration of standard of care DAPT (aspirin in combination with either clopidogrel, prasugrel, or ticagrelor) and still be on treatment: * ≥ 6 months after an elective PCI * ≥ 12 months after experiencing an ACS (irrespective of revascularization at the time of ACS; thus patients treated by PCI, CABG, or medically managed can be considered)
Exclusion criteria
* Deemed to be at high risk of bleeding, active bleeding or history of major bleeding Stroke within 1 month or any history of hemorrhagic or lacunar stroke * Estimated glomerular filtration rate \<15 mL/min by MDRD equation * Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy * 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. * History of hypersensitivity or known contraindication for rivaroxaban. * 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 * Any known hepatic disease associated with coagulopathy * 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 * Known contraindication to any study related procedures * Hemoglobin ≤9 mg/dL * Platelet count \<80x106/mL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA) | 30 days | The primary end point of this study will be the comparison of MPA% measured by LTA using the CATF cocktail as agonist between DAPT and low-dose rivaroxaban plus aspirin for each DAPT regimen |
Countries
United States
Participant flow
Pre-assignment details
Patients treated with either aspirin (81mg/qd) plus clopidogrel, aspirin (81mg/qd) plus ticagrelor (90mg/bid), or aspirin (81mg/qd) plus prasugrel (10mg/bid) were identified. Each cohort was randomized 1:1 to either maintain DAPT or to DPI. DPI consists in treatment with aspirin (81mg/qd) plus rivaroxaban (2.5mg/bid). Patients randomized to DAPT will continue their guideline recommended DAPT regimens.
Participants by arm
| Arm | Count |
|---|---|
| Aspirin and Clopidogrel aspirin 81 mg/qd plus clopidogrel 75mg/qd for 30 days
Clopidogrel: Patients on aspirin and plavix will be randomized to either continue with aspirin and plavix or to switch to aspirin and rivaroxaban
aspirin: all patients will remain on aspirin | 15 |
| Aspirin and Rivaroxaban From Aspirin and Clopidogrel aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days
aspirin: all patients will remain on aspirin
rivaroxaban: Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban | 15 |
| Aspirin and Prasugrel aspirin 81 mg/qd plus prasugrel 10mg/qd for 30 days
Prasugrel: Patients on aspirin and prasugrel will be randomized to either continue with aspirin and prasugrel or to switch to aspirin and rivaroxaban
aspirin: all patients will remain on aspirin | 15 |
| Aspirin and Rivaroxaban From Aspirin and Prasugrel aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days
aspirin: all patients will remain on aspirin
rivaroxaban: Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban | 15 |
| Aspirin and Ticagrelor aspirin 81 mg/qd plus ticagrelor 60mg/bid for 30 days
ticagrelor: Patients on aspirin and ticagrelor will be randomized to either continue with aspirin and ticagrelor or to switch to aspirin and rivaroxaban
aspirin: all patients will remain on aspirin | 15 |
| Aspirin and Rivaroxaban From Aspirin and Ticagrelor aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days
aspirin: all patients will remain on aspirin
rivaroxaban: Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban | 15 |
| Total | 90 |
Baseline characteristics
| Characteristic | Aspirin and Rivaroxaban From Aspirin and Clopidogrel | Aspirin and Clopidogrel | Aspirin and Prasugrel | Aspirin and Rivaroxaban From Aspirin and Prasugrel | Aspirin and Ticagrelor | Aspirin and Rivaroxaban From Aspirin and Ticagrelor | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 7.2 | 63.4 years STANDARD_DEVIATION 7.9 | 61.1 years STANDARD_DEVIATION 6.6 | 61.1 years STANDARD_DEVIATION 9 | 56.5 years STANDARD_DEVIATION 8.8 | 60.9 years STANDARD_DEVIATION 9.4 | 61.3 years STANDARD_DEVIATION 8.4 |
| Diabetes mellitus | 9 Participants | 11 Participants | 10 Participants | 5 Participants | 12 Participants | 7 Participants | 54 Participants |
| Previous percutaneous coronary intervention | 12 Participants | 13 Participants | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 85 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 6 Participants | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 10 Participants | 12 Participants | 10 Participants | 11 Participants | 61 Participants |
| Region of Enrollment United States | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 15 Participants | 90 Participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 12 Participants | 12 Participants | 8 Participants | 11 Participants | 60 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 3 Participants | 3 Participants | 7 Participants | 4 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 1 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA)
The primary end point of this study will be the comparison of MPA% measured by LTA using the CATF cocktail as agonist between DAPT and low-dose rivaroxaban plus aspirin for each DAPT regimen
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aspirin and Clopidogrel | Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA) | 27 percentage of MPA |
| Aspirin and Rivaroxaban From Aspirin and Clopidogrel | Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA) | 53 percentage of MPA |
| Aspirin and Prasugrel | Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA) | 20 percentage of MPA |
| Aspirin and Rivaroxaban From Aspirin and Prasugrel | Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA) | 4 percentage of MPA |
| Aspirin and Ticagrelor | Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA) | 15 percentage of MPA |
| Aspirin and Rivaroxaban From Aspirin and Ticagrelor | Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA) | 20 percentage of MPA |