SWAP-AC: Switching From DAPT to Dual Pathway Inhibition With Low-dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease

Sponsor

University of Florida (Other)

Overall Status

Completed

CT.gov ID

NCT04006288

Collaborator

Janssen, LP (Industry)

Enrollment

Location

Arms

32.3

Actual Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Clopidogrel Drug: Prasugrel Drug: ticagrelor Drug: aspirin Drug: rivaroxaban	Phase 4

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel 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.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.

Masking:

None (Open Label)

Masking Description:

laboratory personnel running pharmacodynamic testing will be blinded to treatment assignment.

Primary Purpose:

Treatment

Official Title:

Switching From Standard of Care Dual Antiplatelet Treatment (DAPT) Regimens With Aspirin Plus a P2Y12 Inhibitor to Dual Pathway Inhibition (DPI) With Low-dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease: The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) Study

Actual Study Start Date :

Sep 6, 2019

Actual Primary Completion Date :

Jan 31, 2022

Actual Study Completion Date :

May 16, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Aspirin and clopidogrel aspirin 81 mg/qd plus clopidogrel 75mg/qd for 30 days	Drug: Clopidogrel Patients on aspirin and plavix will be randomized to either continue with aspirin and plavix or to switch to aspirin and rivaroxaban Other Names: Plavix Drug: aspirin all patients will remain on aspirin
Experimental: Aspirin and rivaroxaban from aspirin and clopidogrel aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days	Drug: aspirin all patients will remain on aspirin Drug: rivaroxaban Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban Other Names: xarelto
Active Comparator: Aspirin and prasugrel aspirin 81 mg/qd plus prasugrel 10mg/qd for 30 days	Drug: Prasugrel Patients on aspirin and prasugrel will be randomized to either continue with aspirin and prasugrel or to switch to aspirin and rivaroxaban Other Names: Effient Drug: aspirin all patients will remain on aspirin
Experimental: Aspirin and rivaroxaban from aspirin and prasugrel aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days	Drug: aspirin all patients will remain on aspirin Drug: rivaroxaban Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban Other Names: xarelto
Active Comparator: Aspirin and ticagrelor aspirin 81 mg/qd plus ticagrelor 60mg/bid for 30 days	Drug: ticagrelor Patients on aspirin and ticagrelor will be randomized to either continue with aspirin and ticagrelor or to switch to aspirin and rivaroxaban Other Names: brilinta Drug: aspirin all patients will remain on aspirin
Experimental: Aspirin and rivaroxaban from aspirin and ticagrelor aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days	Drug: aspirin all patients will remain on aspirin Drug: rivaroxaban Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban Other Names: xarelto

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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