Phase 4 N=82 Treatment

Pharmacodynamic Effects of Low-dose Rivaroxaban With Antiplatelet Therapies

Coronary Artery Disease · Peripheral Arterial Disease · Atrial Fibrillation

Bottom Line

View on ClinicalTrials.gov: NCT03718429 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jun 2022

Primary outcome: Primary: Platelet-Mediated Global Thrombogenicity — 66; 59; 69; 71 percentage of aggregation — p=0.275

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Rivaroxaban 2.5 mg Tablet (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University of Florida
Primary completion: Feb 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Platelet-Mediated Global Thrombogenicity	66; 59; 69; 71; 63; 74	0.275
PRIMARY Platelet Aggregation Measured by VerifyNow PRU	156; 139; 156; 223; 217; 229	0.488
PRIMARY Thrombin Generation	235; 135; 121; 248; 130; 160	<0.001 sig

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.

Eligibility Criteria

Inclusion criteria

Known CAD (defined as angiographic evidence of >50% coronary artery stenosis or prior coronary revascularization) or PAD (defined as a positive ankle brachial index (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 creatinine clearance [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 <20 mL/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].

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03718429). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.