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

Peripheral Arterial Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05009862
• Other study ID #: 200447
• Secondary ID: 1K23HL151871-01A
• Status: Recruiting
• Phase: Phase 4
• Start date: April 19, 2022
• Est. completion date: March 1, 2025

Study information

• Verified date: October 2023
• Source: Vanderbilt University Medical Center
• Contact: Paige V Yates, BS
• Phone: (615) 322-0930
• Email: paige.v.yates[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: March 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• History of peripheral artery disease (PAD) defined as:

1. Previous aorto-femoral bypass surgery, limb bypass surgery, or percutaneous transluminal angioplasty revascularization of the iliac or infra-inguinal arteries, or

2. Previous limb or foot amputation for arterial vascular disease, or

3. History of one or more of the following:

1. An ankle/arm blood pressure (BP) ratio < 0.90, or

2. Significant peripheral artery stenosis (=50%) documented by angiography, or by duplex ultrasound

• 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 <30% or New York Heart Association (NYHA) class III or IV symptoms
• Estimated glomerular filtration rate <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

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• Thrombosis

Intervention

Drug:
• Rivaroxaban 2.5 Mg Oral Tablet
rivaroxaban 2.5 milligrams twice daily
• Placebo
placebo
• Aspirin 81Mg Ec Tab
aspirin 81 milligrams

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days
Secondary	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.	Baseline to 37 days