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

Coronary Artery Disease Clinical Trial

— ARTCAP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06280976
• Other study ID #: 23.0001
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2024
• Est. completion date: January 31, 2029

Study information

• Verified date: April 2024
• Source: University of Louisville
• Contact: Dinesh Kalra, MD
• Phone: 502-588-7010
• Email: dinesh.kalra[@]louisville.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 31, 2029
• Est. primary completion date: January 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Heart Attack
• Myocardial Infarction
• Plaque, Atherosclerotic

Intervention

Drug:
• Statin
high intensity statin (eg atorvastatin 80 mg daily)
• Aspirin tablet
aspirin 81 mg po qd
• Nexlizet
bempedoic acid-ezetimibe 180-10 mg po qd
• LEQVIO
inclisiran SQ as per product insert
• Vascepa
icosapent ethyl 2g PO BID
• Jardiance
empagliflozin 10 mg PO QD
• Colchicine
Colchicine 0.5 MG po qd

Locations

Country	Name	City	State
United States	University of Louisville School of Medicine, Division of Cardiovascular Diseases	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
University of Louisville

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plaque quantification	Quantification of plaque including total plaque, calcified plaque, non-calcified plaque, and partially calcified plaque. Units: mm3	Baseline, 18 months
Primary	Characterization of plaque to evaluate for high-risk features - positive remodeling	Characterization of plaque to evaluate for high-risk features - positive remodeling Units: no units (yes or no)	Baseline, 18 months
Primary	Quantification of stenosis	Quantification of stenosis by using CT-FFR. Unit: percentage	Baseline, 18 months
Primary	Quantification of pericoronary fat attenuation.	Quantification of pericoronary and epicardial fat attenuation. Unit: Fat attenuation index [ranging from -190 to -30 Hounsfield units (HU)]	Baseline, 18 months
Primary	Characterization of plaque to evaluate for high-risk features - low CT attenuation	Characterization of plaque to evaluate for high-risk features - low CT attenuation Units: no units (yes or no)	Baseline, 18 months
Primary	Characterization of plaque to evaluate for high-risk features - napkin-ring sign	Characterization of plaque to evaluate for high-risk features - napkin-ring sign Units: no units (yes or no)	Baseline, 18 months
Primary	Quantification of epicardial fat attenuation.	Quantification of epicardial fat attenuation. Unit: Fat attenuation index [ranging from -190 to -30 Hounsfield units (HU)]	Baseline, 18 months
Secondary	Major adverse cardiac and cardiovascular events (MACCE)	Number of participants with adjusted events including non-fatal myocardial infarction, stroke, transient ischemic attack, urgent revascularization, cardiovascular hospitalization, hospitalization for heart failure, and cardiovascular death.; Unit: number of events	5 years
Secondary	Polygenic risk score (PRS)	Polygenic risk score (PRS) to estimate the participant's genetic susceptibility for coronary artery disease, assessed via blood draw.; Unit: No units (weighted score ranging from 0-100)	Baseline
Secondary	Next generation sequencing (NGS)	Next generation sequencing (NGS) to identify mutations associated with coronary artery disease, assessed via blood draw.; Unit: Mutation in disease-genes	Baseline
Secondary	Change in Lipoprotein (a)	Change in Lipoprotein (a) level as assessed via blood draw. Unit: nmol/L	Baseline, 9 and 18 months
Secondary	Change in myeloperoxidase (MPO) activity	Change in myeloperoxidase (MPO) activity, as assessed via blood draw. Unit: µU/mg	Baseline, 9 and 18 months
Secondary	Change in trimethylamine-N-oxide (TMAO) levels	Change in trimethylamine-N-oxide (TMAO) levels, assessed via blood draw. Unit: µM	Baseline, 9 and 18 months
Secondary	Change in lipoprotein-associated phospholipase A2 (Lp-PLA2) levels	Change in lipoprotein-associated phospholipase A2 (Lp-PLA2) levels, as assessed by blood draw.; Unit: ng/mL	Baseline, 9 and 18 months
Secondary	Change in interleukin-6 (IL-6) levels	Change in interleukin-6 (IL-6) levels, as assessed by blood draw. Unit: pg/mL	Baseline, 9 and 18 months
Secondary	Change in high sensitivity C-creative protein (HS-CRP) levels	Change in high sensitivity C-creative protein (HS-CRP) levels as assessed by blood draw.; Units: mg/mL	Baseline, 9 and 18 months
Secondary	Buffy coat for chromatin immunoprecipitation (ChIP)	Buffy coat for chromatin immunoprecipitation (ChIP) as assessed by blood draw. Unit: Genomic locations of binding of various proteins involved in coronary plaque formation	Baseline, 9 and 18 months
Secondary	Change in high sensitivity Troponin (HS-Tn)	Change in high sensitivity Troponin (HS-Tn), as assessed by blood draw. Unit: ng/mL	Baseline, 9 and 18 months
Secondary	Change in natriuretic peptide (BNP, NT-pro BNP	Change in natriuretic peptide (BNP, NT-pro BNP), as assessed by blood draw. Unit: pg/mL	Baseline, 9 and 18 months
Secondary	Change in levels of open reading frame 1 protein (ORF1p)	Change in levels of open reading frame 1 protein (ORF1p), as assessed by blood draw using enzyme-linked immunosorbent assay (ELISA) or western blotting.; Unit: µg/mL	Baseline, 9 and 18 months