The Impact of Factor Xa Inhibition on Thrombosis, Platelet Activation, and Endothelial Function in Peripheral Artery Disease

March 30, 2026 updated by: Aaron W. Aday, MD, MSc, Vanderbilt University Medical Center
The purpose of this study is to understand how the drug rivaroxaban improves symptoms associated with peripheral artery disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The Primary Investigator's central hypothesis is that activation of thrombotic pathways and downstream effectors of factor Xa signaling contribute to the development of PAD and its complications.

Aim 1: To assess the impact of rivaroxaban on macrovascular endothelial function in a randomized, double-blind, placebo-controlled crossover intervention in humans with PAD.

Aim 2: To assess the impact of rivaroxaban on PAR-1-mediated platelet activation in addition to its pleiotropic effects on thrombosis, thrombolysis, and inflammation in a randomized, double-blind, placebo-controlled crossover intervention in humans with PAD.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

History of peripheral artery disease (PAD) defined as:

  • Previous aorto-femoral bypass surgery, limb bypass surgery, or percutaneous transluminal angioplasty revascularization of the iliac or infra-inguinal arteries, or
  • Previous limb or foot amputation for arterial vascular disease, or
  • An ankle/arm blood pressure (BP) ratio less than 0.90, or
  • Significant peripheral artery stenosis (≥50%) documented by angiography, or by duplex ultrasound, or
  • An ankle-brachial index (ABI) greater than 1.4 with a toe-brachial index (TBI) less than 0.7 AND
  • Willing and able to provide written informed consent
  • Receiving aspirin therapy prior to enrollment

Exclusion Criteria:

  • High risk of bleeding
  • Stroke within 1 month of any history of hemorrhagic or lacunar stroke
  • Severe heart failure with known ejection fraction less than 30% or New York Heart Association (NYHA) class III or IV symptoms
  • Estimated glomerular filtration rate less than 15 mL/min/1.73m2
  • 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 to rivaroxaban or aspirin
  • 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
  • Upcoming invasive procedure within 3 months
  • Invasive procedure within the prior 1 month
  • Being treated for an active infection
  • Acute or chronic limb-threatening ischemia
  • Known contraindication to any study related procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control
Participants will receive 81mg daily of aspirin + placebo for 30 days.
Drug: Placebo
placebo
Drug: Aspirin 81Mg Ec Tab
aspirin 81 milligrams
Experimental: Intervention
Participants will receive 81mg of aspirin + rivaroxaban 2.5mg twice daily for 30 days.
Drug: Aspirin 81Mg Ec Tab
aspirin 81 milligrams
Drug: Rivaroxaban 2.5 Mg Oral Tablet
rivaroxaban 2.5 milligrams twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery
Time Frame: Baseline to 37 days
FMD will be measured by forearm high-resolution ultrasonography after treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
Endogenous PAR-1 activation as measured by flow cytometry
Time Frame: Baseline to 37 days
Endogenous PAR-1 activation, a novel marker of platelet activation, will be measured by flow cytometry, following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo. The unit of measure will be relative fluorescence.
Baseline to 37 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prothrombin time
Time Frame: Baseline to 37 days
Prothrombin time will be measured using turbidimetric assays following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo. The unit of measure will be in seconds.
Baseline to 37 days
Partial thromboplastin time
Time Frame: Baseline to 37 days
Partial thromboplastin time will be measured using turbidimetric assays following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo. The unit of measure will be seconds.
Baseline to 37 days
von Willebrand factor (vWF)
Time Frame: Baseline to 37 days
Blood levels of von Willebrand factor will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
D-Dimer
Time Frame: Baseline to 37 days
Blood levels of D-dimer will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
High-sensitivity C-reactive protein.
Time Frame: Baseline to 37 days
Blood levels of high-sensitivity C-reactive protein will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo. The unit of measure will be mg/L.
Baseline to 37 days
Tumor necrosis factor-alpha
Time Frame: Baseline to 37 days
Blood levels of tumor necrosis factor-alpha will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
Interleukin-1beta
Time Frame: Baseline to 37 days
Blood levels of interleukin-1beta will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
Interleukin-6
Time Frame: Baseline to 37 days
Blood levels of interleukin-6 will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
Soluble intercellular adhesion molecule-1 (slCAM-1)
Time Frame: Baseline to 37 days
Blood levels of soluble intercellular adhesion molecule-1 (slCAM-1) will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
Monocyte chemoattractant protein-1 (MCP-1)
Time Frame: Baseline to 37 days
Blood levels of monocyte chemoattractant protein-1 (MCP-1) will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
Plasminogen activator inhibitor 1 (PAI-1)
Time Frame: Baseline to 37 days
Blood levels of plasminogen activator inhibitor 1 (PAI-1) will be measured following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
CD41a (Integrin alpha-II-beta)
Time Frame: Baseline to 37 days
CD41a, a marker of platelet activation, will be measured by flow cytometry following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days
CD62p (P-Selectin)
Time Frame: Baseline to 37 days
CD62p, a marker of platelet activation, will be measured by flow cytometry following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Baseline to 37 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Aaron W Aday, MD, VUMC Cardiovascular Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 19, 2022

Primary Completion (Actual)

July 1, 2025

Study Completion (Actual)

July 1, 2025

Study Registration Dates

First Submitted

July 9, 2021

First Submitted That Met QC Criteria

August 16, 2021

First Posted (Actual)

August 18, 2021

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 30, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200447
  • 5K23HL151871 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Peripheral Arterial Disease

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in South Korea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe