Atherosclerotic Cardiovascular DiseasePhase 4BETTERNCT05761444
Effectiveness and Safety Study of Early add-on of Ezetimibe With Atorvastatin in Very High-risk Patients
A Phase 4 study testing Atozet 10/40 mg or 10/80 mg and Lipitor 40 mg or 80 mg in people with Atherosclerotic Cardiovascular Disease, run by Organon and Co at 7 sites in South Korea.
Trial summary
This study aims to confirm the effectiveness of ezetimibe add-on therapy on LDL-C levels compared to atorvastatin monotherapy, especially in very high-risk patients. We intend to lay the foundation for a standard treatment for these patients through ezetimibe add on lipid-lowering therapy. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Atherosclerotic Cardiovascular Disease
- What is being tested?
- Atozet 10/40 mg or 10/80 mg and Lipitor 40 mg or 80 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 137 participants
- Where
- 7 sitesSouth Korea
- Study dates
- 26 Jul 2023to 15 Oct 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who are ≥ 30 years old.
- Patients with very high-risk*: clinical or unequivocal on imaging ASCVD. ASCVD includes previous ACS (MI or UA), stable angina, coronary revascularization (percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), and other arterial revascularization procedures), stroke and transient ischaemic attack (TIA), and peripheral arterial disease (Mach F 2020).
- Patients (a) who failed to achieve their target LDL-C goals with low and/or moderate intensity statin mono therapy for ≥ 4 weeks or (b) who are statin-naïve or have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment
- rosuvastatin < 10 mg, atorvastatin < 40 mg, and all dose of pitavastatin, simvastatin, lovastatin, pravastatin, and fluvastatin (Team G 2020).
- Patients with LDL-C levels ≥ 70 mg/dL
- Patients who are willing to maintain TLC throughout the study.
- Patients who are willing to provide written informed consent prior to study enrollment.
Who cannot join
- Patients with hypersensitivity to ezetimibe, atorvastatin or any of its inactive ingredients.
- Patients with active liver disease or unexplained persistent elevations of hepatic transaminase levels. (aspartate transaminase (AST) or alanine transaminase (ALT) > 3 x upper limit of normal (ULN)).
- Patients who have predisposing conditions with muscle disease (i.e., rhabdomyolysis or myopathy) or neuromuscular disease.
- Patients with myasthenia gravis.
- Female patients who are pregnant or have a potential to be pregnant and nursing.
- Patients who are taking glecaprevir and pibrentasvir.
Show all 13Show fewer
- Patients with hereditary problems of galactose intolerance, lapp lactase deficiency, or of glucose-galactose malabsorption.
- Patients with disease known to influence serum lipids or lipoproteins excluding dyslipidemia.
- Patients with a history of cancer within 5 years.
- Patients whose life expectancy is less than 6 months due to their medical conditions.
- Patients with any condition or situation that might pose a risk to the participant or interfere with participation in the study.
- Patients who have received any investigational medicine within 12 weeks of written informed consent or are going to receive during the clinical trial period.
- Patients who are judged to be difficult to conduct clinical trials according to the judgment of the investigator.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
South Korea7 sites
Keimyung University Dongsan Medical Center
Daegu, Gyeongsangbuk-do, 42601
Inje University Ilsan-Paik Hospital
Goyang-si, Gyeonggi-do, 10380
Chonnam National University Hospital
Gwangju, Jeollanam-do, 61469
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Eunpyeong St. Mary's Hospital
Seoul, Eunpyeong-gu, 03312
Kangbuk Samsung Hospital
Seoul, 03181
Ulsan University Hospital
Ulsan, Gyeongsangnam-do, 44033
About this study
Official title: A Phase 4, Multicenter, Randomized, Open-label, Active-controlled Study to Evaluate the Effectiveness and Safety of Early add-on of Ezetimibe With Atorvastatin in Very High-risk Patients
This study aims to confirm the effectiveness of ezetimibe add-on therapy on LDL-C levels compared to atorvastatin monotherapy, especially in very high-risk patients. We intend to lay the foundation for a standard treatment for these patients through ezetimibe add on lipid-lowering therapy.
- Conditions
- Atherosclerotic Cardiovascular Disease
- Being tested
- Atozet 10/40 mg or 10/80 mg, Lipitor 40 mg or 80 mg
- Keywords
- Very high-risk patients' Atherosclerotic cardiovascular disease (ASCVD)
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atozet 10/40 mg or 10/80 mgDrug
Atozet 10/40 mg or 10/80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily
Lipitor 40 mg or 80 mgDrug
Lipitor 40 mg or 80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily
| Study group | Role | What they receive |
|---|---|---|
| Eze/Ato: Ezetimibe/Atorvastatin | Experimental | Participants will receive ezetimibe/atorvastatin 10/40 mg QD from Visit 2 (Day 1) to Visit 3 (Week 6). If the LDL-C target is reached (LDL-C < 55 mg/dL) at Visit 3, maintain the dose to Visit 4 (Week 12). If the LDL-C target level is not reached at Visit 3, dose is increased to ezetimibe/atorvastatin 10/80 mg QD from Visit 3 to Visit 4. Receives: Drug: Atozet 10/40 mg or 10/80 mg |
| Ato: Atorvastatin | Active comparator | Participants will receive atorvastatin 40 mg QD from Visit 2 (Day 1) to Visit 3 (Week 6). If the LDL-C target is reached (LDL-C < 55 mg/dL) at Visit 3, maintain the dose to Visit 4 (Week 12). If the LDL-C target is not reached at Visit 3, dose is increased to atorvastatin 80 mg QD from Visit 3 to Visit 4. Receives: Drug: Lipitor 40 mg or 80 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 6
Blood samples were collected to determine the LDL-C values. The percentage change from baseline was defined as 100 x (LDL-C value at 6 weeks - LDL-C value at baseline)/LDL-C value at baseline. Baseline was defined as the last non-missing measurement taken prior to reference start date.
Measured: Baseline (Day 1) and Week 6
Secondary outcomes (6)
Percentage of Participants Who Achieved Low-Density Lipoprotein Cholesterol Goal of <55 mg/dL at Weeks 6 and 12
Blood samples were collected to determine the LDL-C values. Participants with LDL-C <55 mg/dL were identified. Percentages are rounded off to the hundredth decimal place.
Measured: Weeks 6 and 12
Percentage of Participants Who Achieved Low-Density Lipoprotein Cholesterol Goal of <70 mg/dL at Weeks 6 and 12
Blood samples were collected to determine the LDL-C values. Participants with LDL-C <70 mg/dL were identified. Percentages are rounded off to the hundredth decimal place.
Measured: Weeks 6 and 12
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12
Blood samples were collected to determine the LDL-C values. The percentage change from baseline was defined as 100 x (LDL-C value at 12 weeks - LDL-C value at baseline)/LDL-C value at baseline. Baseline was defined as the last non-missing measurement taken prior to reference start date.
Measured: Baseline (Day 1) and Week 12
Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C), Non-High-Density Lipoprotein Cholesterol (Non-HDL-C), Triglycerides, and Total Cholesterol at Weeks 6 and 12
Blood samples were collected to determine the HDL-C, non-HDL-C, triglycerides, and total cholesterol values. The percentage change from baseline for HDL-C was defined as 100 x (HDL-C value at 6 or 12 weeks - HDL-C value at baseline)/HDL-C value at baseline. The percentage change from baseline for non-HDL-C was defined as 100 x (non-HDL-C value at 6 or 12 weeks - non-HDL-C value at baseline)/non-HDL-C value at baseline. The percentage change from baseline for triglycerides was defined as 100 x (triglycerides value at 6 or 12 weeks - triglycerides value at baseline)/triglycerides value at baseline. The percentage change from baseline for total cholesterol was defined as 100 x (total cholesterol value at 6 or 12 weeks - total cholesterol value at baseline)/total cholesterol value at baseline. Baseline was defined as the last non-missing measurement taken prior to reference start date.
Measured: Baseline (Day 1) and Weeks 6 and 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) at Weeks 6 and 12
An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with that product. An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. A TEAE was defined as AEs that first occurred or worsened in severity on or after the first administration of the study treatment during the treatment period.
Measured: From the first dose administration of the study treatment (Day 1) up to Week 6; From the first dose administration of the study treatment (Day 1) up to Week 12
Number of Participants With Treatment-Emergent Adverse Event Leading to the Premature Discontinuation of the Study
An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with that product. An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. A TEAE was defined as AEs that first occurred or worsened in severity on or after the first administration of the study treatment during the treatment period.
Measured: From the first dose administration of the study treatment (Day 1) up to Week 6; From the first dose administration of the study treatment (Day 1) up to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2023
- Study start26 Jul 2023
- Primary completion4 Sep 2024
- Study completion15 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atherosclerotic Cardiovascular DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Responsible party
- Sponsor
- Investigators
- WonYoung Lee, Study director, Organon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05761444
- Sponsor's protocol ID
- OG-KORATO-001
- Acronym
- BETTER
- Status last verified
- Oct 2024
- First submitted
- 27 Feb 2023
- Last updated
- 9 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kang SH, Kwon SU, Lee JY, Seo SM, Nam CW, Park GM, Hong YJ, Lee WY, Jang JE, Chae IH. The role of early ezetimibe combination with atorvastatin in patients with atherosclerotic cardiovascular disease. BMC Cardiovasc Disord. 2026 Feb 11;26(1):233. doi: 10.1186/s12872-026-05594-2.
PubMed 41673582
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4, Multicenter, Randomized, Open-label, Active-controlled Study to Evaluate the Effectiveness and Safety of Early add-on of Ezetimibe With Atorvastatin in Very High-risk Patients
- ClinicalTrials.gov ID
- NCT05761444
- Acronym / sponsor ID
- BETTER / OG-KORATO-001
- Conditions
- Atherosclerotic Cardiovascular Disease
- Keywords
- Very high-risk patients' Atherosclerotic cardiovascular disease (ASCVD)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Study start
- 26 Jul 2023 (actual)
- Primary completion
- 4 Sep 2024 (actual)
- Study completion
- 15 Oct 2024 (actual)
- First posted
- 9 Mar 2023 (actual)
- Results
- Posted 9 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to confirm the effectiveness of ezetimibe add-on therapy on LDL-C levels compared to atorvastatin monotherapy, especially in very high-risk patients. We intend to lay the foundation for a standard treatment for these patients through ezetimibe add on lipid-lowering therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eze/Ato: Ezetimibe/Atorvastatin | Experimental | Drug: Atozet 10/40 mg or 10/80 mgParticipants will receive ezetimibe/atorvastatin 10/40 mg QD from Visit 2 (Day 1) to Visit 3 (Week 6). If the LDL-C target is reached (LDL-C < 55 mg/dL) at Visit 3, maintain the dose to Visit 4 (Week 12). If the LDL-C target level is not reached at Visit 3, dose is increased to ezetimibe/atorvastatin 10/80 mg QD from Visit 3 to Visit 4. |
| Ato: Atorvastatin | Active comparator | Drug: Lipitor 40 mg or 80 mgParticipants will receive atorvastatin 40 mg QD from Visit 2 (Day 1) to Visit 3 (Week 6). If the LDL-C target is reached (LDL-C < 55 mg/dL) at Visit 3, maintain the dose to Visit 4 (Week 12). If the LDL-C target is not reached at Visit 3, dose is increased to atorvastatin 80 mg QD from Visit 3 to Visit 4. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients who are ≥ 30 years old.
- Patients with very high-risk*: clinical or unequivocal on imaging ASCVD. ASCVD includes previous ACS (MI or UA), stable angina, coronary revascularization (percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), and other arterial revascularization procedures), stroke and transient ischaemic attack (TIA), and peripheral arterial disease (Mach F 2020).
- Patients (a) who failed to achieve their target LDL-C goals with low and/or moderate intensity statin mono therapy for ≥ 4 weeks or (b) who are statin-naïve or have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment
- Patients with LDL-C levels ≥ 70 mg/dL
- Patients who are willing to maintain TLC throughout the study.
Key exclusion criteria (13 listed)
- Patients with hypersensitivity to ezetimibe, atorvastatin or any of its inactive ingredients.
- Patients with active liver disease or unexplained persistent elevations of hepatic transaminase levels. (aspartate transaminase (AST) or alanine transaminase (ALT) > 3 x upper limit of normal (ULN)).
- Patients who have predisposing conditions with muscle disease (i.e., rhabdomyolysis or myopathy) or neuromuscular disease.
- Patients with myasthenia gravis.
- Female patients who are pregnant or have a potential to be pregnant and nursing.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atozet 10/40 mg or 10/80 mgAtozet 10/40 mg or 10/80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily | Drug | Eze/Ato: Ezetimibe/Atorvastatin |
| Lipitor 40 mg or 80 mgLipitor 40 mg or 80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily | Drug | Ato: Atorvastatin |
Primary outcome
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 6
Time frame: Baseline (Day 1) and Week 6
Blood samples were collected to determine the LDL-C values. The percentage change from baseline was defined as 100 x (LDL-C value at 6 weeks - LDL-C value at baseline)/LDL-C value at baseline. Baseline was defined as the last non-missing measurement taken prior to reference start date.
6 secondary outcomes
Percentage of Participants Who Achieved Low-Density Lipoprotein Cholesterol Goal of <55 mg/dL at Weeks 6 and 12
Time frame: Weeks 6 and 12
Percentage of Participants Who Achieved Low-Density Lipoprotein Cholesterol Goal of <70 mg/dL at Weeks 6 and 12
Time frame: Weeks 6 and 12
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12
Time frame: Baseline (Day 1) and Week 12
Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C), Non-High-Density Lipoprotein Cholesterol (Non-HDL-C), Triglycerides, and Total Cholesterol at Weeks 6 and 12
Time frame: Baseline (Day 1) and Weeks 6 and 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) at Weeks 6 and 12
Time frame: From the first dose administration of the study treatment (Day 1) up to Week 6; From the first dose administration of the study treatment (Day 1) up to Week 12
Number of Participants With Treatment-Emergent Adverse Event Leading to the Premature Discontinuation of the Study
Time frame: From the first dose administration of the study treatment (Day 1) up to Week 6; From the first dose administration of the study treatment (Day 1) up to Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41673582Kang SH, Kwon SU, Lee JY, Seo SM, Nam CW, Park GM, Hong YJ, Lee WY, Jang JE, Chae IH. The role of early ezetimibe combination with atorvastatin in patients with atherosclerotic cardiovascular disease. BMC Cardiovasc Disord. 2026 Feb 11;26(1):233. doi: 10.1186/s12872-026-05594-2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
WonYoung Lee study director
Organon
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atozet 10/40 mg or 10/80 mg and Lipitor 40 mg or 80 mg in people with Atherosclerotic Cardiovascular Disease, run by Organon and Co at 7 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 6 (time frame: Baseline (Day 1) and Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05761444, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2025.