Switching From DAPT to Dual Pathway Inhibition With Low-dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Intervention: Clopidogrel; Prasugrel; ticagrelor; aspirin; rivaroxaban
Intervention description: Patients on aspirin and plavix will be randomized to either continue with aspirin and plavix or to switch to aspirin and rivaroxaban; Patients on aspirin and prasugrel will be randomized to either continue with aspirin and prasugrel or to switch to aspirin and rivaroxaban; Patients on aspirin and ticagrelor will be randomized to either continue with aspirin and ticagrelor or to switch to aspirin and rivaroxaban; all patients will remain on aspirin; Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban
Intervention MeSH terms: Aspirin; Rivaroxaban; Clopidogrel; Ticagrelor; Prasugrel Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
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.
Masking: None (Open Label)
Masking description: laboratory personnel running pharmacodynamic testing will be blinded to treatment assignment.
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: dual antiplatelet therapy; rivaroxaban; pharmacodynamic

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).
    

Eligibility criteria:

        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