CClinicalTrials.gg
Sign In
Not yet recruitingNCT07474649Updated Sep 18, 2026

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

A Phase 3 interventional study of Bempedoic acid and Ezetimibe in Coronary Atherosclerosis, Mixed Dyslipidemia and Hypercholesterolemia, sponsored by Daiichi Sankyo. Not yet recruiting at 12 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-18.

Sponsored by Daiichi Sankyo · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
103
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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. HeartFlow is the imaging analysis vendor.

02

Conditions studied

  • Coronary Atherosclerosis
  • Mixed Dyslipidemia
  • Hypercholesterolemia

Keywords

  • Coronary atherosclerosis
  • Primary non-familial hypercholesterolaemia
  • Mixed dyslipidaemia
  • Bempedoic acid
  • Ezetimibe
  • Atorvastatin
  • Rosuvastatin
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

  1. Age ≥18 years
  2. Having provided informed consent for participation in this trial
  3. Lipid-lowering treatment-naïve

  4. 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')
  5. Able to provide informed consent

Exclusion criteria

Exclusion Criteria:

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

  1. Known or suspected heterozygous or homozygous familial hypercholesterolaemia or familial combined hyperlipidaemia
  2. 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.
  3. Not expected to remain on a stable dose of high intensity triple therapy for the duration of the trial.
  4. History of myocardial infarction, stroke, or peripheral artery disease (PAD), and/or coronary revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG])
  5. 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
  6. 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])
  7. Known history of gout and/or uric acid levels at Screening ≥6.8 mg/dL
  8. Known estimated glomerular filtration rate (eGFR) \<40 mL/min/1.73m² and/or receiving dialysis
  9. Active malignancy (not including non-melanoma skin cancer)
  10. Pregnant or breastfeeding
  11. Body mass index (BMI) >35 kg/m²
  12. Anticipated life expectancy \<52 weeks at the discretion of the local investigator
  13. 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
  14. Suspicion of acute coronary syndrome (where acute myocardial infarction and unstable angina have not been ruled out)
  15. Complex congenital heart disease
  16. 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
  17. Cardiac arrythmia or tachycardia with significant likelihood of resulting in poor PCD-CTA image quality (especially atrial fibrillation or frequent premature beats)
  18. Intracoronary stents
  19. Prior pacemaker, internal defibrillator, or abandoned lead implantation
  20. Prosthetic heart valves
  21. Contraindications to contrast media or other medications needed for proper imaging (e.g., beta blockers and nitroglycerin)
  22. 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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
103 participants (estimated)

Study arms

  • Experimental
    Bempedoic acid (BA)/ezetimibe (EZE) fixed dose combination (FDC) with rosuvastatin or atorvastatin

    Treatment-naïve participants with coronary atherosclerosis and primary non-familial hypercholesterolaemia or mixed dyslipidaemia who will receive daily treatment with BA/EZE FDC, together with either 20 mg rosuvastatin or 40 mg atorvastatin.

    Drug: Bempedoic acid · Drug: Ezetimibe · Drug: Rosuvastatin · Drug: Atorvastatin

Interventions

  • DrugBempedoic acid

    FDC: 180 mg

  • DrugEzetimibe

    FDC: 10 mg

  • DrugRosuvastatin

    20 mg dose

  • DrugAtorvastatin

    40 mg dose

05

What researchers measure

Primary outcomes

  1. Annualised change in percentage plaque burden (Δ%PB)

    This endpoint will evaluate the effectiveness of the triple therapy in reducing plaque burden (PB).

    Time frame: Baseline up to 12 months

Secondary outcomes

  1. Key Secondary: Annualised change in normalised non-calcified plaque volume (PV)

    This endpoint will assess the efficacy of the triple therapy by evaluating changes in plaque composition and morphology.

    Time frame: Baseline up to 12 months

  2. 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)

    This endpoint will evaluate the potential impact of the triple therapy on total plaque volume (TPV) regression, non-calcified PV regression, and low attenuation PV regression.

    Time frame: Baseline up to 12 months

  3. Change in the absolute Agatston coronary artery calcium (CAC) score

    This endpoint will evaluate the potential impact of the triple therapy on coronary calcification. CAC measures the total area and density of calcified plaque in the heart's arteries, ranging from 0 to over 400. A score of 0 indicates no plaque, while higher scores indicate increased risk of cardiovascular events, with \>400 indicating extensive disease.

    Time frame: Baseline up to 12 months

  4. Annualised ΔTotal Plaque Volume (TPV)

    This endpoint will evaluate the effectiveness of the triple therapy in reducing TPV.

    Time frame: Baseline up to 12 months

  5. Percentage of participants with regression in TPV (i.e., negative ΔTPV)

    This endpoint will assess the proportion of participants exhibiting regression in TPV with triple therapy.

    Time frame: Baseline up to 12 months

  6. Absolute annualised change in fractional flow reserve derived from computed tomography (FFRCT) of the vessel with the lowest FFR at Baseline

    This endpoint will assess changes in non-invasive coronary flow reserve.

    Time frame: Baseline up to 12 months

  7. 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])

    This endpoint will assess changes in non-invasive coronary flow reserve.

    Time frame: Baseline up to 12 months

  8. Mean absolute changes in atherosclerosis-related biomarker total cholesterol

    This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.

    Time frame: Baseline up to 12 months

  9. Mean absolute changes in atherosclerosis-related biomarker low-density lipoprotein cholesterol (LDL-C)

    This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.

    Time frame: Baseline up to 12 months

  10. Mean absolute changes in atherosclerosis-related biomarker high-density lipoprotein cholesterol (HDL-C)

    This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.

    Time frame: Baseline up to 12 months

  11. Mean absolute changes in atherosclerosis-related biomarker non-high-density lipoprotein cholesterol (non-HDL-C)

    This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.

    Time frame: Baseline up to 12 months

  12. Mean absolute changes in atherosclerosis-related biomarkers lipoprotein a (Lp(a)) and apolipoprotein B (apoB)

    This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.

    Time frame: Baseline up to 12 months

  13. Mean absolute changes in atherosclerosis-related biomarker high-sensitive C reactive protein (hs-CRP)

    This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.

    Time frame: Baseline up to 12 months

  14. Annualised changes in Framingham steatosis index (FSI) and fibrosis-4 (Fib-4)

    This endpoint will assess the potential impact of the triple therapy on measures of liver health.

    Time frame: Baseline up to 12 months

  15. Cumulative incidence of adverse events (AEs) under triple therapy during the trial

    This endpoint will monitor and assess adverse events (AEs) under triple treatment.

    Time frame: Baseline up to 12 months

  16. Rate of treatment discontinuation during the trial

    This endpoint will to determine the rate and reasons for treatment discontinuation among trial participants receiving triple therapy.

    Time frame: Baseline up to 12 months

06

Study locations

12 sites
  • Charité - Universitätsmedizin Berlin
    Berlin, 12203, Germany
    • Principal Investigator · Contact
  • UKE Hamburg
    Hamburg, Germany
    • Principal Investigator · Contact
  • Universität Mainz
    Mainz, 55131, Germany
    • Principal Investigator · Contact
  • Heidelberg University
    Mannheim, 68167, Germany
    • Principal Investigator · Contact
  • IRCCS Policlinico San Donato
    Milan, 20097, Italy
    • Principal Investigator · Contact
  • Cardiology, IRCCS San Raffaele Scientific Institute
    Milan, 20132, Italy
    • Principal Investigator · Contact
  • AOU Federico II di Napoli
    Naples, 80131, Italy
    • Principal Investigator · Contact
  • IRCCS Ospedale Sacro Cuore - Don Calabria
    Negrar, 37024, Italy
    • Principal Investigator · Contact
  • Hospital Quironsalud Barcelona
    Barcelona, 08023, Spain
    • Principal Investigator · Contact
  • Hospital San Rafael
    Madrid, 28016, Spain
    • Principal Investigator · Contact
  • CUN (Clínica Universitaria de Navarra)
    Madrid, 28027, Spain
  • Hospital Universitario Quironsalud Madrid
    Madrid, 28223, Spain
    • Principal Investigator · Contact
07

References and documents

Individual participant data

Plan to share: Yes — De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Supporting information: Study protocol, Sap, Icf

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07474649
Lead sponsor
Daiichi Sankyo
Responsible party
Sponsor
First posted
Mar 16, 2026
Start date
Sep 30, 2026 (estimated)
Primary completion
Jun 1, 2028 (estimated)
Completion
Oct 2, 2028 (estimated)
Last update
Sep 18, 2026

Study contacts

Daiichi Sankyo Contact for Clinical Trial Information
Contact
CTRinfo_us@daiichisankyo.com
908-992-6400

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Coronary Artery Disease→

Other studies from this sponsor

Daiichi Sankyo

Start the discussion