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

Sponsor

Asan Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05797376

Collaborator

Bayer (Industry)

Enrollment

Location

Arms

51.3

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis of Artery Coronary Artery Disease Peripheral Arterial Disease Carotid Stenosis	Drug: Rivaroxaban 2.5mg	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

92 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Aug 24, 2021

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

The percent change (%) in Most Diseased segment(MDS) Target-to-Background Ratio(TBR) of the index vessel [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

Secondary Outcome Measures

Change from baseline in whole vessel Target-to-Background Ratio(TBR) [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.
Change from baseline in hs-C-Ractive Protein(CRP) and lipid profiles [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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