Clinical trial NCT06280976: Aggressive Risk-Prevention Therapies for Coronary Atherosclerotic Plaque (ART-CAP)
Official title: Aggressive Risk-Prevention Therapies for Coronary Atherosclerotic Plaque (ART-CAP)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Atherosclerosis
Heart Attack
Keywords: Coronary artery plaque
Coronary CT angiogram
Lead sponsor: University of Louisville
Sponsor class: OTHER
First posted: 2024-02-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PROBE design: Prospective Randomized Open Label Blinded End-point
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Plaque quantification
timeFrame: Baseline, 18 months
measure: Characterization of plaque to evaluate for high-risk features - positive remodeling
timeFrame: Baseline, 18 months
measure: Quantification of stenosis
timeFrame: Baseline, 18 months
measure: Quantification of pericoronary fat attenuation.
timeFrame: Baseline, 18 months
measure: Characterization of plaque to evaluate for high-risk features - low CT attenuation
timeFrame: Baseline, 18 months
measure: Characterization of plaque to evaluate for high-risk features - napkin-ring sign
timeFrame: Baseline, 18 months
measure: Quantification of epicardial fat attenuation.
timeFrame: Baseline, 18 months
Secondary outcomes:
measure: Major adverse cardiac and cardiovascular events (MACCE)
timeFrame: 5 years
measure: Polygenic risk score (PRS)
timeFrame: Baseline
measure: Next generation sequencing (NGS)
timeFrame: Baseline
measure: Change in Lipoprotein (a)
timeFrame: Baseline, 9 and 18 months
measure: Change in myeloperoxidase (MPO) activity
timeFrame: Baseline, 9 and 18 months
measure: Change in trimethylamine-N-oxide (TMAO) levels
timeFrame: Baseline, 9 and 18 months
measure: Change in lipoprotein-associated phospholipase A2 (Lp-PLA2) levels
timeFrame: Baseline, 9 and 18 months
measure: Change in interleukin-6 (IL-6) levels
timeFrame: Baseline, 9 and 18 months
measure: Change in high sensitivity C-creative protein (HS-CRP) levels
timeFrame: Baseline, 9 and 18 months
measure: Buffy coat for chromatin immunoprecipitation (ChIP)
timeFrame: Baseline, 9 and 18 months
measure: Change in high sensitivity Troponin (HS-Tn)
timeFrame: Baseline, 9 and 18 months
measure: Change in natriuretic peptide (BNP, NT-pro BNP
timeFrame: Baseline, 9 and 18 months
measure: Change in levels of open reading frame 1 protein (ORF1p)
timeFrame: Baseline, 9 and 18 months
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville School of Medicine, Division of Cardiovascular Diseases
state: Kentucky
Study officials:
affiliation: University of Louisville School of Medicine
name: Dinesh Kalra, MD
role: PRINCIPAL_INVESTIGATOR
References: