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

Primary Purpose

Atherosclerosis of Artery, Coronary Artery Disease, Peripheral Arterial Disease

Status
Recruiting
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Rivaroxaban 2.5mg
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Atherosclerosis of Artery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Asan Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Rivaroxaban + Aspirin group

Aspirin group

Arm Description

patients are prescribed aspirin at a daily dose of 100mg and Rivaroxaban (2.5 mg twice a day)

patients are prescribed aspirin at a daily dose of 100mg

Outcomes

Primary Outcome Measures

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

Full Information

First Posted
March 9, 2023
Last Updated
June 13, 2023
Sponsor
Asan Medical Center
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT05797376
Brief Title
Effects of aSPIrin Versus Aspirin Plus Low-dose RIvaroxaban on Carotid aTherosclerotic Plaque Inflammation
Acronym
SPIRIT
Official Title
Effects of aSPIrin Versus Aspirin Plus Low-dose RIvaroxaban on Carotid aTherosclerotic Plaque Inflammation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 24, 2021 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
Collaborators
Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerosis of Artery, Coronary Artery Disease, Peripheral Arterial Disease, Carotid Stenosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
92 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rivaroxaban + Aspirin group
Arm Type
Experimental
Arm Description
patients are prescribed aspirin at a daily dose of 100mg and Rivaroxaban (2.5 mg twice a day)
Arm Title
Aspirin group
Arm Type
No Intervention
Arm Description
patients are prescribed aspirin at a daily dose of 100mg
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban 2.5mg
Other Intervention Name(s)
Xarelto 2.5mg
Intervention Description
patients are prescribed aspirin at a daily dose of 100mg and Rivaroxaban (2.5 mg twice a day)
Primary Outcome Measure Information:
Title
The percent change (%) in Most Diseased segment(MDS) Target-to-Background Ratio(TBR) of the index vessel
Description
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
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change from baseline in whole vessel Target-to-Background Ratio(TBR)
Description
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.
Time Frame
12 months
Title
Change from baseline in hs-C-Ractive Protein(CRP) and lipid profiles
Description
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)
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Seungbin Park, RN
Phone
+822-2045-3396
Email
tmdqls0101@naver.com
First Name & Middle Initial & Last Name or Official Title & Degree
Seung-whan Lee, Investigator
Phone
82230103170
Email
seungwlee@amc.seoul.kr
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seung-Whan Lee, MD
Phone
82230103170
Email
seungwlee@amc.seoul.kr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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