Effects of aSPIrin Versus Aspirin Plus Low-dose RIvaroxaban on Carotid aTherosclerotic Plaque Inflammation (SPIRIT)

December 23, 2024 updated by: Seung-Whan Lee, M.D., Ph.D., Asan Medical Center

Primary Study Objective : To compare the effects of low-dose rivaroxaban plus aspirin versus aspirin on atherosclerotic plaque inflammation using serial FDG Positron Emission Tomography/Computed Tomography(PET-CT) imaging of carotid artery and ascending aorta.

Secondary Study Objective : To compare the effects of low-dose rivaroxaban plus aspirin versus aspirin on biomarkers including high-sensitivity C-Reactive Protein(CRP) and lipid profiles.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Cardiovascular disease is a major health problem across the world. The age-adjusted death rate for cardiovascular disease has significantly decreased during recent decades, and this decline is related to the widespread use of evidence-based medicines. However, even upon optimal medical therapies, patients remains at a substantial residual risk for acute coronary syndrome (ACS) or acute ischemic stroke(AIS), requiring new therapeutic approaches. Plaque rupture and subsequent thrombus formation is the most common cause of ACS and AIS. Atherosclerosis is a chronic immune-inflammatory disorder. Inflammation is believed to be critically important to plaque rupture by destroying the fibrous cap, thereby predisposing to ACS and AIS. Cross-talk between coagulation and inflammatory pathway via protease-activated receptor (PAR) activation has been recognized . Factor Xa is responsible for promoting inflammation, which participate in the atherosclerotic process and plaque destabilization either directly via activation of PARs or indirectly through the generation of thrombin .

In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, the rate of a composite of cardiovascular death, stroke, or myocardial infarction was lower by 24% with low-dose rivaroxaban (2.5 mg twice daily) plus aspirin than with aspirin alone among patients with stable atherosclerotic vascular disease, but the rate of major bleeding was higher by 70%. Interestingly, the rate of stroke was remarkably lower by 42% with rivaroxaban plus aspirin than with aspirin alone. The substantial net clinical benefits seen with rivaroxaban plus aspirin may not be fully explained by their anti-thrombotic effect alone, suggesting pleiotropic effects coupled with factor Xa antagonism. Besides its role in hemostasis and thrombosis, low-dose rivaroxaban may inhibit atherosclerotic plaque inflammation and decrease plaque destabilization. To test this hypothesis, the investigators will compare the effects of aspirin versus aspirin plus low-dose rivaroxaban on carotid atherosclerotic plaque inflammation using serial 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography/Computed Tomography(PET-CT) imaging of carotid artery and ascending aorta.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
92

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men or women at least 18 years of age inclusive
  • Asymptomatic Carotid Artery Disease (diameter stenosis, 20-80%)
  • Inclusion criteria for the COMPASS trial (stable Peripheral Artery Disease(PAD); or stable Coronary Artery Disease(CAD) with 1 of age over 65 years, or age <65 years plus atherosclerosis less than 2 vascular beds or less than 2 additional risk factors)
  • FDG Postron Emission Tomography(PET)/Computed tomogrphy(CT) shows hot uptakes at carotid artery (with or without hot uptake at ascending aorta)
  • The patient or guardian agrees to the study protocol and the schedule of clinical and FDG Postron Emission Tomography(PET)/Computed tomogrphy(CT) follow-up, and provides informed, written consent, as approved by the Institutional Review Board/Ethical Committee.

Exclusion Criteria:

  • Patients treated with carotid endarterectomy or stent placement
  • Contraindications to rivaroxaban or aspirin.
  • Stroke in 1 month or any hemorrhagic or lacuna stroke
  • Need for dual antiplatelet therapy or oral anticoagulant therapy
  • Severe left ventricular dysfunction (ejection fraction < 30%)
  • Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study.
  • Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (alanine aminotransferase(ALT) or aspartate aminotransferase(AST) > 3 times upper limit of normal).
  • Unwillingness or inability to comply with the procedures described in this protocol.
  • Patient's pregnant or breast-feeding or child-bearing potential.
  • Insulin requiring diabetes
  • Patients who have experienced critical organ bleeding within 1 year

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rivaroxaban + Aspirin group
patients are prescribed aspirin at a daily dose of 100mg and Rivaroxaban (2.5 mg twice a day)
Drug: Rivaroxaban 2.5mg
patients are prescribed aspirin at a daily dose of 100mg and Rivaroxaban (2.5 mg twice a day)
Other Names:
  • Xarelto 2.5mg
No Intervention: Aspirin group
patients are prescribed aspirin at a daily dose of 100mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The percent change (%) in Most Diseased segment(MDS) Target-to-Background Ratio(TBR) of the index vessel
Time Frame: 12 months

The percent change (%) in Most Diseased segment(MDS) Target-to-Background Ratio(TBR) of the index vessel defined as (Most Diseased segment(MDS) Target-to-Background Ratio(TBR) at 12 months - Most Diseased segment(MDS) Target-to-Background Ratio(TBR) at baseline)/(Most Diseased segment(MDS) Target-to-Background Ratio(TBR) at baseline)*100.

* Index vessel: carotid artery with the highest 18-FDG uptake at baseline
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in whole vessel Target-to-Background Ratio(TBR)
Time Frame: 12 months
Change from baseline in whole vessel Target-to-Background Ratio(TBR) within the index vessel, Most Diseased segment(MDS) Target-to-Background Ratio(TBR), & whole vessel Target-to-Background Ratio(TBR) of the aorta.
12 months
Change from baseline in hs-C-Ractive Protein(CRP) and lipid profiles
Time Frame: 12 months
Change from baseline in hs-C Ractive Protein(CRP) in mg/dL and lipid profiles(total cholesterol in mg/dL, Triglyceride(TG) in mg/dL, High Density Lipoprotein(HDL) in mg/dL, Low Density Lipoprotein(LDL) in mg/dL)
12 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Asan Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bayer

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 24, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 12, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 5, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 9, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 4, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 23, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020-1322

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

No

Studies a U.S. FDA-regulated device product

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.

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