Aggressive Risk-Prevention Therapies for Coronary Atherosclerotic Plaque (ART-CAP)

NCT ID: NCT06280976

Last Updated: 2025-03-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2025-01-01

Brief Summary

The purpose of this study is to evaluate the role of coronary CT angiogram (CCTA) as a superior guide for the assessment of coronary artery plaque and guiding treatment decisions. The investigators also assess the impact of preventive cardiovascular drugs on the plaque to improve patient outcomes. Participants aged 18-80 years, at intermediate or high-risk for coronary artery disease, with non-obstructive plaque on initial CCTA, will be enrolled in this study. They will be randomized into Standard of Care (SOC) vs. Aggressive Therapy (AT) groups. Both groups will undergo dietary and lifestyle interventions. Follow-up will consist of blood tests and clinic visits at baseline, 9 months, and 18 months. The second CCTA will be performed at 18 months to assess the change in plaque burden, characteristics, ischemia and pericoronary/epicardial fat.

Detailed Description

ART-CAP (Aggressive Risk-Prevention Therapies for Coronary Atherosclerotic Plaque ) is a prospective randomized open-label trial with blinded end-point. This research project aims to study the role of coronary computed tomographic angiography (CCTA) as a superior guide for the direct assessment and monitoring of the impact of preventive cardiovascular drugs on coronary artery plaque for better clinical decision-making and improving patient outcomes. Participants aged 18-80 years, at intermediate or high-risk (10-year ASCVD risk of 5-20% or >20%; calculated based on age, gender, race, history of smoking, diabetes mellitus, hypertension, hyperlipidemia, and family history of premature CAD, with/without symptoms suggestive of coronary disease) who has non-obstructive plaque on CCTA (stenosis of 0-39% or 40-69% with FFR-CT >0.8), will be enrolled. Participants with a history of heart attack, coronary stents or bypass surgery, recent stroke, severe valvular heart disease, pulmonary hypertension, NYHA class 3 or 4 heart failure, recent heart failure hospitalization, active cancer, life expectancy of <1 year, end-stage kidney or liver disease, pregnancy or uncontrolled psychiatric illness, will be excluded.

Participants will be randomly assigned to two groups - Standard of Care (SOC, 100 pts) vs. Aggressive Therapy (AT, 100 pts). Both groups will receive dietary and lifestyle interventions. SOC will be treated with statin and/or aspirin as per the ACC guidelines. AT group will be treated with statin, aspirin, nexlizet, leqvio, vascepa, jardiance, and colchicine. Follow-up will consist of blood tests and clinic visits at baseline, 9 months, and 18 months. At baseline, participants will undergo Polygenic Risk Score (PRS) and next-generation sequencing (NGS) for a South Asian gene panel. Biomarker evaluations at baseline, 9 months, and 18 months include lipid profiles, inflammatory markers, cardiac biomarkers, and buffy coat analysis for CHIP, along with standard blood tests including CBC and CMP. Additionally, echocardiographic evaluation will be performed at baseline and 18 months.

After 18 months of medical treatment, a repeat CCTA will be performed to evaluate primary endpoints of the percentage change in plaque burden (total, non-calcified and calcified), plaque characteristics including high-risk features, ischemia value for the most severe lesion, and pericoronary/epicardial fat attenuation. Patient will be followed for additional 5 years for MACCE (major adverse cardiovascular and cerebrovascular events).

Conditions

Coronary Artery Disease; Atherosclerosis; Heart Attack

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SOC: Statin ± Aspirin (per ACC guidelines)

The SOC group: participant receive routine care as per cardiologist. Study doctor will prescribe medications that they choose themselves.

Group Type: ACTIVE_COMPARATOR

Statin

Intervention Type: DRUG

high intensity statin (eg atorvastatin 80 mg daily)

Aspirin tablet

Intervention Type: DRUG

aspirin 81 mg po qd

AT: Statin, Aspirin, Nexlizet, Leqvio, Vascepa, Jardiance, Colchicine

An AT group: FDA-approved drugs will be used to reduce cholesterol and cardiovascular risk.

Group Type: EXPERIMENTAL

Statin

Intervention Type: DRUG

high intensity statin (eg atorvastatin 80 mg daily)

Aspirin tablet

Intervention Type: DRUG

aspirin 81 mg po qd

Nexlizet

Intervention Type: DRUG

bempedoic acid-ezetimibe 180-10 mg po qd

LEQVIO

Intervention Type: DRUG

inclisiran SQ as per product insert

Vascepa

Intervention Type: DRUG

icosapent ethyl 2g PO BID

Jardiance

Intervention Type: DRUG

empagliflozin 10 mg PO QD

Colchicine

Intervention Type: DRUG

Colchicine 0.5 MG po qd

Interventions

Statin

high intensity statin (eg atorvastatin 80 mg daily)

Intervention Type: DRUG

Aspirin tablet

aspirin 81 mg po qd

Intervention Type: DRUG

Nexlizet

bempedoic acid-ezetimibe 180-10 mg po qd

Intervention Type: DRUG

LEQVIO

inclisiran SQ as per product insert

Intervention Type: DRUG

Vascepa

icosapent ethyl 2g PO BID

Intervention Type: DRUG

Jardiance

empagliflozin 10 mg PO QD

Intervention Type: DRUG

Colchicine

Colchicine 0.5 MG po qd

Intervention Type: DRUG

Other Intervention Names

atorvastatin; aspirin 81 mg; bempedoic acid-ezetimibe; inclisiran; icosapent ethyl; empagliflozin

Eligibility Criteria

Inclusion Criteria

Non-obstructive atherosclerotic coronary artery plaque (stenosis of 0-39% or stenosis of 40-69% with FFR-CT >0.8) in a major epicardial vessel > 2 mm in diameter.

Exclusion Criteria

1. coronary/PAD/carotid revascularization or ischemic stroke or TIA within 6 months prior to enrollment

2. Valvular heart disease of moderate or worse severity or requiring interventional procedures or surgery

3. LVEF <35% in the past 12 months

4. Pulmonary hypertension with PASP>50 mm Hg in the past 12 months

5. Myocarditis or pericarditis in the past 12 months

6. Known Cardiomyopathy (hypertrophic, infiltrative, restrictive, dilated, etc.)

7. Heart failure NYHA class 3 or 4

8. Hospitalization for heart failure in the preceding 6 months

9. Life expectancy of <1 year

10. An organ-transplant recipient or if felt to require listing for solid organ transplantation during study status

11. Inability to give informed consent

12. Active malignancy (except basal cell skin cancer)

13. Cirrhosis

14. ESRD

15. Pregnancy or planning to conceive during the study period

16. Known intolerance or perceived contraindication to any of the study drugs during the study period including statins or aspirin if indicated

17. eGFR<30 ml/min/m2

18. Inability to receive iodinated contrast for CCTA

19. Chronic immunosuppression therapy

20. Uncontrolled psychiatric illness

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Louisville

OTHER

Sponsor Role: lead

Responsible Party

Dinesh Kalra, MD

Professor, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dinesh Kalra, MD

Role: PRINCIPAL_INVESTIGATOR

University of Louisville School of Medicine

Locations

University of Louisville School of Medicine, Division of Cardiovascular Diseases

Louisville, Kentucky, United States

Countries

United States

Other Identifiers

23.0001

Identifier Type: -

Identifier Source: org_study_id