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

NCT05009862 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: 2004475K23HL151871
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to understand how the drug rivaroxaban improves symptoms associated with peripheral artery disease.

Conditions

Peripheral Arterial Disease

Keywords

Peripheral Artery Disease; PAD; Thrombosis; Rivaroxaban; Anticoagulant

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline to 37 days

Secondary Outcomes (13)

• Prothrombin time

  Baseline to 37 days

• Partial thromboplastin time

  Baseline to 37 days

• von Willebrand factor (vWF)

  Baseline to 37 days

• D-Dimer

  Baseline to 37 days

• High-sensitivity C-reactive protein.

  Baseline to 37 days

Study Arms (2)

Control

PLACEBO COMPARATOR

Participants will receive 81mg daily of aspirin + placebo for 30 days.

Drug: Placebo; Drug: Aspirin 81Mg Ec Tab

Intervention

EXPERIMENTAL

Participants will receive 81mg of aspirin + rivaroxaban 2.5mg twice daily for 30 days.

Drug: Rivaroxaban 2.5 Mg Oral Tablet; Drug: Aspirin 81Mg Ec Tab

Interventions

Rivaroxaban 2.5 Mg Oral Tablet DRUG

rivaroxaban 2.5 milligrams twice daily

Intervention

Placebo DRUG

placebo

Control

Aspirin 81Mg Ec Tab DRUG

aspirin 81 milligrams

Control; Intervention

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Peripheral Arterial Disease; Thrombosis

Interventions

Rivaroxaban; Aspirin

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Aaron W Aday, MD

  VUMC Cardiovascular Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Division of Cardiovascular Medicine

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: August 18, 2021
• Study Start: April 19, 2022
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)