Peripheral Arterial DiseasePhase 4NCT05009862
The Impact of Factor Xa Inhibition on Thrombosis, Platelet Activation, and Endothelial Function in Peripheral Artery Disease
A Phase 4 study testing Rivaroxaban 2.5 Mg Oral Tablet and Aspirin 81Mg Ec Tab in people with Peripheral Arterial Disease, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to understand how the drug rivaroxaban improves symptoms associated with peripheral artery disease. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- Rivaroxaban 2.5 Mg Oral Tablet and Aspirin 81Mg Ec Tab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Apr 2022to 1 Jul 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
The purpose of this study is to understand how the drug rivaroxaban improves symptoms associated with peripheral artery disease.
Read the 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.
- Conditions
- Peripheral Arterial Disease
- Being tested
- Rivaroxaban 2.5 Mg Oral Tablet, Placebo, Aspirin 81Mg Ec Tab
- Keywords
- Peripheral Artery Disease, PAD, Thrombosis, Rivaroxaban, Anticoagulant
- Medical subject headings
- Peripheral Arterial Disease, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rivaroxaban 2.5 Mg Oral TabletDrug
rivaroxaban 2.5 milligrams twice daily
PlaceboDrug
placebo
Aspirin 81Mg Ec TabDrug
aspirin 81 milligrams
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Participants will receive 81mg daily of aspirin + placebo for 30 days. Receives: Drug: Placebo; Drug: Aspirin 81Mg Ec Tab |
| Intervention | Experimental | Participants will receive 81mg of aspirin + rivaroxaban 2.5mg twice daily for 30 days. Receives: Drug: Rivaroxaban 2.5 Mg Oral Tablet; Drug: Aspirin 81Mg Ec Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery
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.
Measured: Baseline to 37 days
Endogenous PAR-1 activation as measured by flow cytometry
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.
Measured: Baseline to 37 days
Secondary outcomes (13)
Prothrombin time
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.
Measured: Baseline to 37 days
Partial thromboplastin time
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.
Measured: Baseline to 37 days
von Willebrand factor (vWF)
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.
Measured: Baseline to 37 days
D-Dimer
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.
Measured: Baseline to 37 days
High-sensitivity C-reactive protein.
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.
Measured: Baseline to 37 days
Tumor necrosis factor-alpha
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.
Measured: Baseline to 37 days
Interleukin-1beta
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.
Measured: Baseline to 37 days
Interleukin-6
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.
Measured: Baseline to 37 days
Soluble intercellular adhesion molecule-1 (slCAM-1)
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.
Measured: Baseline to 37 days
Monocyte chemoattractant protein-1 (MCP-1)
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.
Measured: Baseline to 37 days
Plasminogen activator inhibitor 1 (PAI-1)
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.
Measured: Baseline to 37 days
CD41a (Integrin alpha-II-beta)
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.
Measured: Baseline to 37 days
CD62p (P-Selectin)
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.
Measured: Baseline to 37 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2021
- Study start19 Apr 2022
- Primary completion1 Jul 2025
- Study completion1 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Aaron W. Aday, MD, MSc, Vanderbilt University Medical Center
- Investigators
- Aaron W Aday, MD, Principal investigator, VUMC Cardiovascular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05009862
- Sponsor's protocol ID
- 200447
- Other IDs
- 5K23HL151871
- Status last verified
- Jul 2026
- First submitted
- 9 Jul 2021
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Factor Xa Inhibition on Thrombosis, Platelet Activation, and Endothelial Function in Peripheral Artery Disease
- ClinicalTrials.gov ID
- NCT05009862
- Acronym / sponsor ID
- 200447
- Conditions
- Peripheral Arterial Disease
- Keywords
- Peripheral Artery Disease, PAD, Thrombosis, Rivaroxaban, Anticoagulant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 19 Apr 2022 (actual)
- Primary completion
- 1 Jul 2025 (actual)
- Study completion
- 1 Jul 2025 (actual)
- First posted
- 18 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to understand how the drug rivaroxaban improves symptoms associated with peripheral artery disease.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: Placebo, Drug: Aspirin 81Mg Ec TabParticipants will receive 81mg daily of aspirin + placebo for 30 days. |
| Intervention | Experimental | Drug: Rivaroxaban 2.5 Mg Oral Tablet, Drug: Aspirin 81Mg Ec TabParticipants will receive 81mg of aspirin + rivaroxaban 2.5mg twice daily for 30 days. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rivaroxaban 2.5 Mg Oral Tabletrivaroxaban 2.5 milligrams twice daily | Drug | Intervention |
| Placeboplacebo | Drug | Control |
| Aspirin 81Mg Ec Tabaspirin 81 milligrams | Drug | Control, Intervention |
Primary outcome
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.
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.
13 secondary outcomes
Prothrombin time
Time frame: Baseline to 37 days
Partial thromboplastin time
Time frame: Baseline to 37 days
von Willebrand factor (vWF)
Time frame: Baseline to 37 days
D-Dimer
Time frame: Baseline to 37 days
High-sensitivity C-reactive protein.
Time frame: Baseline to 37 days
Tumor necrosis factor-alpha
Time frame: Baseline to 37 days
Interleukin-1beta
Time frame: Baseline to 37 days
Interleukin-6
Time frame: Baseline to 37 days
Soluble intercellular adhesion molecule-1 (slCAM-1)
Time frame: Baseline to 37 days
Monocyte chemoattractant protein-1 (MCP-1)
Time frame: Baseline to 37 days
Plasminogen activator inhibitor 1 (PAI-1)
Time frame: Baseline to 37 days
CD41a (Integrin alpha-II-beta)
Time frame: Baseline to 37 days
CD62p (P-Selectin)
Time frame: Baseline to 37 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for Peripheral Arterial Disease
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aaron W Aday, MD principal investigator
VUMC Cardiovascular Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rivaroxaban 2.5 Mg Oral Tablet and Aspirin 81Mg Ec Tab in people with Peripheral Arterial Disease, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery (time frame: Baseline to 37 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.