Pharmacodynamic Effects of Low-dose Rivaroxaban With Antiplatelet Therapies

• Status: Completed
• Trial end date: 2020-08-30
• Target enrollment: 0
• Participant gender: All

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.

To date there is very little data, and not conducted in human subjects, on the interplay between anti-Xa blockade with low-dose rivaroxaban and antiplatelet therapies, and in particular how this affects profiles of platelet reactivity and thrombin generation. Given the potential role for the use of low-dose rivaroxaban for the prevention of ischemic recurrences in patients with atherothrombotic disease manifestations, including coronary artery disease (CAD) and peripheral arterial disease (PAD), the study team proposes a prospective pharmacodynamic (PD) investigation assessing the impact of low-dose rivaroxaban when used in combination with antiplatelet treatment regimens commonly used in clinical practice.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Florida
• Collaborator: Janssen Scientific Affairs, LLC
• Treatments: Aspirin; Clopidogrel; Rivaroxaban; Ticagrelor

Criteria

Inclusion criteria:

• Known CAD (defined as angiographic evidence of >50% coronary artery stenosis or prior coronary revascularization) or PAD (defined as a positive ABI or prior revascularization)

• on treatment with either aspirin (81mg/qd), aspirin (81mg/qd) plus clopidogrel (75mg/qd), or aspirin (81mg/qd) plus ticagrelor (90mg/bid) for at least 3 months per standard of care OR

• Atrial fibrillation (paroxysmal, persistent or permanent) on treatment with rivaroxaban 20 mg qd (if CrCl >50 mL/min) or 15 mg qd (if CrCl 15 - 50 mL/min) per standard of care. Patients with concomitant CAD or PAD who are also taking antiplatelet medications are not eligible. However, if these are only on oral anticoagulation with rivaroxaban (and no antiplatelet therapy) the person will be eligible.

Exclusion criteria:

• Active pathological bleeding, history of clinically significant bleeding events, or deemed at increased risk of bleeding.

• CrCL <20mL/min

• Any clinical indication to be on triple antithrombotic therapy (DAPT plus an oral anticoagulant)

• An acute coronary event in the past 90 days

• Prior hemorrhagic stroke or intracranial hemorrhage

• Ischemic stroke/transient ischemic attack in the past 6 months

• Chronic use of nonsteroidal anti-inflammatory drugs

• On treatment with combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan) or inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort).

• Known moderate or severe hepatic impairment (Child-Pugh B and C)

• Prior hypersensitivity reaction to rivaroxaban

• On treatment with prasugrel in the past 10 days.

• Platelet count <80x106/mL

• Hemoglobin <10g/dL

• Hemodynamic instability

• Pregnant females [women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study].