A Study of Bempedoic Acid/Ezetimibe/High-intensity Statin in Patients Without Cardiovascular Events

Official title

Effects of Bempedoic Acid/Ezetimibe/High-intensity Statin on Plaque Regression and Stabilisation of Coronary Atherosclerosis Among Patients Without Cardiovascular Events

Overview

The overall objective of the trial is to evaluate the effect of the triple therapy consisting of bempedoic acid (BA), ezetimibe (EZE), and high-intensity atorvastatin or rosuvastatin on changes in coronary plaque burden and plaque morphology in patients with coronary atherosclerosis without significant obstructive coronary artery disease and without prior history of an ischemic vascular event.

Detailed description

The primary objective is to evaluate the effectiveness of the triple therapy in reducing plaque burden.

The key secondary objective is to assess the efficacy of the triple therapy by evaluating changes in plaque composition and morphology.

Interventions

• Drug Bempedoic acid
  FDC: 180 mg
• Drug Ezetimibe
  FDC: 10 mg
• Drug Rosuvastatin
  20 mg dose
• Drug Atorvastatin
  40 mg dose

Primary outcome measures

• Annualised change in percentage plaque burden (Δ%PB) [Time frame: Baseline up to 12 months]

Secondary outcome measures (12)

• Key Secondary: Annualised change in normalised non-calcified plaque volume (PV) [Time frame: Baseline up to 12 months]
• Percentage of participants with regression in normalised total plaque volume (TPV), normalised non-calcified PV, and normalised low attenuation PV at EoT (i.e., ΔPV and Δnon-calcified PV, and Δlow-attenuation PV) [Time frame: Baseline up to 12 months]
• Change in the absolute Agatston coronary artery calcium (CAC) score [Time frame: Baseline up to 12 months]
• Annualised ΔTotal Plaque Volume (TPV) [Time frame: Baseline up to 12 months]
• Percentage of participants with regression in TPV (i.e., negative ΔTPV) [Time frame: Baseline up to 12 months]
• Absolute annualised change in fractional flow reserve derived from computed tomography (FFRCT) of the vessel with the lowest FFR at Baseline [Time frame: Baseline up to 12 months]
• Absolute annualised change in FFRCT of the average of 3 main epicardial coronary arteries (left anterior descending artery [LAD], circumflex artery [Cx], right coronary artery [RCA]) [Time frame: Baseline up to 12 months]
• Mean absolute changes in atherosclerosis-related biomarker total cholesterol [Time frame: Baseline up to 12 months]
• Mean absolute changes in atherosclerosis-related biomarker low-density lipoprotein cholesterol (LDL-C) [Time frame: Baseline up to 12 months]
• Mean absolute changes in atherosclerosis-related biomarker high-density lipoprotein cholesterol (HDL-C) [Time frame: Baseline up to 12 months]
• Mean absolute changes in atherosclerosis-related biomarker non-high-density lipoprotein cholesterol (non-HDL-C) [Time frame: Baseline up to 12 months]
• Mean absolute changes in atherosclerosis-related biomarkers lipoprotein a (Lp(a)) and apolipoprotein B (apoB) [Time frame: Baseline up to 12 months]

Eligibility criteria

Inclusion criteria

In order to be eligible to participate in this trial, a potential participant must meet all of the following criteria:

• Age ≥18 years
• Having provided informed consent for participation in this trial
• Lipid-lowering treatment-naïve
• Presence of extensive coronary atherosclerosis meeting all of the criteria below:

• Unequivocal atherosclerosis in ≥5 American Heart Association (AHA) coronary segments (corresponding to a risk equivalent of obstructive coronary artery disease) and coronary artery disease - reporting and data system (CAD-RADS) category 1, 2, or 3
• Not expected to be a candidate for revascularisation during the duration of the trial
• Untreated LDL-C ≥2.6 mmol/L and ≤4.5 mmol/L (where a diet without pharmacological treatment is considered 'untreated')
• Able to provide informed consent

Exclusion criteria

A potential participant who meets any of the following criteria will be excluded from participation in this trial:

• Known or suspected heterozygous or homozygous familial hypercholesterolaemia or familial combined hyperlipidaemia
• Known contraindication for BA, EZE, atorvastatin, and/or rosuvastatin. A participant with a contraindication for atorvastatin, can be assigned to triple therapy with rosuvastatin, and vice versa.
• Not expected to remain on a stable dose of high intensity triple therapy for the duration of the trial.
• History of myocardial infarction, stroke, or peripheral artery disease (PAD), and/or coronary revascularisation (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\])
• Significant stenosis in the left main artery (≥50%) or proximal LAD artery (≥70%), or 3-vessel coronary artery disease (≥70% stenosis in major branches), clinically indicated for revascularisation
• Known significant liver disease (e.g., positive hepatitis B or hepatitis C serology) or significant hepatic dysfunction (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] >3 x upper limit of normal \[ULN\])
• Known history of gout and/or uric acid levels at Screening ≥6.8 mg/dL
• Known estimated glomerular filtration rate (eGFR) <40 mL/min/1.73m² and/or receiving dialysis
• Active malignancy (not including non-melanoma skin cancer)
• Pregnant or breastfeeding
• Body mass index (BMI) >35 kg/m²
• Anticipated life expectancy <52 weeks at the discretion of the local investigator
• Requiring emergent procedures or having any evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, severe congestive heart failure (New York Heart Association \[NYHA\] III or IV), or acute pulmonary oedema
• Suspicion of acute coronary syndrome (where acute myocardial infarction and unstable angina have not been ruled out)
• Complex congenital heart disease
• Known or suspected severe valvular heart disease or valvular heart disease anticipated to require intervention within 52 weeks at the discretion of the local investigator
• Cardiac arrythmia or tachycardia with significant likelihood of resulting in poor PCD-CTA image quality (especially atrial fibrillation or frequent premature beats)
• Intracoronary stents
• Prior pacemaker, internal defibrillator, or abandoned lead implantation
• Prosthetic heart valves
• Contraindications to contrast media or other medications needed for proper imaging (e.g., beta blockers and nitroglycerin)
• Use of any experimental or investigational drug within 40 days or 5 half-lives prior to Screening (whichever is longer), or parallel participation in another interventional study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 4 centers

• Charité - Universitätsmedizin Berlin — Berlin
• UKE Hamburg — Hamburg
• Universität Mainz — Mainz
• Heidelberg University — Mannheim

Italy · 4 centers

• IRCCS Policlinico San Donato — Milan
• Cardiology, IRCCS San Raffaele Scientific Institute — Milan
• AOU Federico II di Napoli — Naples
• IRCCS Ospedale Sacro Cuore - Don Calabria — Negrar

Spain · 4 centers

• Hospital Quironsalud Barcelona — Barcelona
• Hospital San Rafael — Madrid
• CUN (Clínica Universitaria de Navarra) — Madrid
• Hospital Universitario Quironsalud Madrid — Madrid

Identifiers

NCT: NCT07474649 · DSE-BMP-0005-CIS-MA · 2025-524625-41

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗