CompletedNCT05761444BETTERUpdated Sep 9, 2025Results posted

Effectiveness and Safety Study of Early add-on of Ezetimibe With Atorvastatin in Very High-risk Patients

A Phase 4 interventional study of Atozet 10/40 mg or 10/80 mg and Lipitor 40 mg or 80 mg in Atherosclerotic Cardiovascular Disease, sponsored by Organon and Co. Completed at 7 sites in South Korea. Open to participants aged 30 Years and older. Per ClinicalTrials.gov, last updated 2025-09-09.

Sponsored by Organon and Co · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 137
Allocation: Randomized
Ages: 30 Years and older
Sex: All

Study 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.

Conditions studied

Atherosclerotic Cardiovascular Disease

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Atherosclerosis 1,567

Keywords

Very high-risk patients' Atherosclerotic cardiovascular disease (ASCVD)

In context

Atherosclerosis

1,567 studies on the registry are indexed under Atherosclerosis; 264 are open to participants now.

This study's enrollment of 137 is above the median of 106 across 882 interventional studies indexed under Atherosclerosis.

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Lead sponsor

Organon and Co is the lead sponsor of 478 studies on the registry; none are open to participants now.

Of its 21 completed or terminated interventional studies of FDA-regulated products, 17 (81%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 30 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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.

Exclusion criteria

Exclusion Criteria:

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.
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.

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 137 participants (actual)

Study arms

Experimental
Eze/Ato: Ezetimibe/Atorvastatin
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.
Drug: Atozet 10/40 mg or 10/80 mg
Active comparator
Ato: Atorvastatin
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.
Drug: Lipitor 40 mg or 80 mg

Interventions

DrugAtozet 10/40 mg or 10/80 mg
Atozet 10/40 mg or 10/80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily
DrugLipitor 40 mg or 80 mg
Lipitor 40 mg or 80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily

What researchers measure

Primary outcomes

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.
Time frame: Baseline (Day 1) and Week 6

Secondary outcomes

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.
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
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.
Time frame: 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.
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
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.
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
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.
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
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.
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

Posted Sep 9, 2025

Participant flow

This Phase 4, open-label, active-controlled study was conducted in very high-risk dyslipidemia participants at 8 centers in South Korea between 26 July 2023 and 15 October 2024.

Participant flow — Overall Study
Milestone	Ezetimibe/Atorvastatin	Atorvastatin
Started	67	70
Treated	67	69
Completed	59	65
Not completed	8	5
Withdrew: Protocol violation	2	1
Withdrew: Adverse event	2	2
Withdrew: Withdrawal by subject	3	2
Withdrew: Other	1	0

Outcome measures

PrimaryPercentage 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.

Time frame:: Baseline (Day 1) and Week 6
Reported as:: Least squares mean · percentage change

Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 6
percentage change	Ezetimibe/Atorvastatin	Atorvastatin
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 6	-48.97 ± 2.71	-27.75 ± 2.47

Statistical analysis

Ezetimibe/Atorvastatin vs Atorvastatin · ANCOVA · p = <0.0001 (The analysis of covariance (ANCOVA) model with treatment group (ezetimibe/atorvastatin, atorvastatin) and history of statin administration (yes, no) as fixed effects and baseline LDL-C as a covariate.) · Least squares (ls) mean difference: -21.22 · 95% CI -29.26 to -13.19

SecondaryPercentage 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.

Time frame:: Weeks 6 and 12
Reported as:: Number · percentage of participants

Percentage of Participants Who Achieved Low-Density Lipoprotein Cholesterol Goal of <55 mg/dL at Weeks 6 and 12
percentage of participants	Ezetimibe/Atorvastatin	Atorvastatin
Week 6	46.2	9.0
Week 12	55.0	15.4

SecondaryPercentage 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.

Time frame:: Weeks 6 and 12
Reported as:: Number · percentage of participants

Percentage of Participants Who Achieved Low-Density Lipoprotein Cholesterol Goal of <70 mg/dL at Weeks 6 and 12
percentage of participants	Ezetimibe/Atorvastatin	Atorvastatin
Week 6	78.5	38.8
Week 12	85.0	58.5

SecondaryPercentage 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.

Time frame:: Baseline (Day 1) and Week 12
Reported as:: Least squares mean · percentage change

Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12
percentage change	Ezetimibe/Atorvastatin	Atorvastatin
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12	-50.37 ± 2.60	-34.41 ± 2.32

Statistical analysis

Ezetimibe/Atorvastatin vs Atorvastatin · ANCOVA · p = <0.0001 (The ANCOVA model with treatment group (ezetimibe/atorvastatin, atorvastatin) and history of statin administration (yes, no) as fixed effects and baseline LDL-C as a covariate.) · Ls mean difference: -15.96 · 95% CI -23.56 to -8.36

SecondaryPercentage 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.

Time frame:: Baseline (Day 1) and Weeks 6 and 12
Reported as:: Mean · percentage change

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
percentage change	Ezetimibe/Atorvastatin	Atorvastatin
Week 6: HDL-C	-2.44 ± 17.837	-0.18 ± 17.479
Week 12: HDL-C	-2.15 ± 18.964	-1.47 ± 17.163
Week 6: non-HDL-C	-35.36 ± 18.378	-24.36 ± 21.625
Week 12: non-HDL-C	-39.97 ± 15.558	-29.48 ± 18.422
Week 6: Triglycerides	-9.67 ± 40.806	-4.94 ± 59.649
Week 12: Triglycerides	-16.67 ± 31.948	-1.49 ± 65.605
Week 6: Total cholesterol	-26.28 ± 14.692	-18.51 ± 15.754
Week 12: Total cholesterol	-29.57 ± 13.563	-22.18 ± 13.722

SecondaryNumber 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.

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
Reported as:: Count of participants · Participants

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) at Weeks 6 and 12
Participants	Ezetimibe/Atorvastatin	Atorvastatin
Week 6: Any TEAE	9	8
Week 6: Any TESAE	3	2
Week 12: Any TEAE	15	13
Week 12: Any TESAE	4	3

SecondaryNumber 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.

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
Reported as:: Count of participants · Participants

Number of Participants With Treatment-Emergent Adverse Event Leading to the Premature Discontinuation of the Study
Participants	Ezetimibe/Atorvastatin	Atorvastatin
Week 6	2	2
Week 12	3	2

Adverse events

Collected over TEAEs are reported from the first dose administration of the study treatment (Day 1) up to end of the study, 12 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Ezetimibe/Atorvastatin	0/67 (0%)	4/67 (6%)	12/67 (17.9%)
Atorvastatin	0/69 (0%)	3/69 (4.3%)	11/69 (15.9%)

Most frequent serious events

Most frequent serious events
Event	Ezetimibe/Atorvastatin	Atorvastatin
Alanine aminotransferase increasedInvestigations	2/67	0/69
Aspartate aminotransferase increasedInvestigations	2/67	0/69
Acute myocardial infarctionCardiac disorders	1/67	0/69
MelaenaGastrointestinal disorders	1/67	0/69
Chest discomfortGeneral disorders	1/67	0/69
DyspnoeaRespiratory, thoracic and mediastinal disorders	1/67	0/69
AnaemiaBlood and lymphatic system disorders	0/67	1/69
HaematocheziaGastrointestinal disorders	0/67	1/69
Gastric cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/67	1/69
Cerebral haemorrhageNervous system disorders	0/67	1/69

Most frequent other events

Showing 10 of 22

Most frequent other events
Event	Ezetimibe/Atorvastatin	Atorvastatin
MyalgiaMusculoskeletal and connective tissue disorders	0/67	3/69
DizzinessNervous system disorders	1/67	2/69
AnaemiaBlood and lymphatic system disorders	1/67	0/69
Iron deficiency anaemiaBlood and lymphatic system disorders	1/67	0/69
Chest discomfortGeneral disorders	1/67	0/69
Chest painGeneral disorders	1/67	0/69
FatigueGeneral disorders	1/67	0/69
OedemaGeneral disorders	1/67	0/69
AST/ALT ratio abnormalInvestigations	1/67	0/69
Alanine aminotransferase increasedInvestigations	1/67	0/69

Baseline characteristics

The Safety analysis set (SAS) included all randomized participants who received at least 1 dose of study treatment.

Age, Continuous
Age, Continuous(years)	Ezetimibe/Atorvastatin	Atorvastatin	Total
Mean	65.1 ± 10.07	64.7 ± 10.66	64.9 ± 10.34

Sex: Female, Male
Sex: Female, Male(Participants)	Ezetimibe/Atorvastatin	Atorvastatin	Total
Female	12	17	29
Male	55	52	107

Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)	Ezetimibe/Atorvastatin	Atorvastatin	Total
Count of participants	—	—	0

Region of Enrollment
Region of Enrollment(Participants)	Ezetimibe/Atorvastatin	Atorvastatin	Total
South Korea	67	69	136

Low-Density Lipoprotein Cholesterol
Low-Density Lipoprotein Cholesterol(mg/dL)	Ezetimibe/Atorvastatin	Atorvastatin	Total
Mean	98.1 ± 23.81	107.8 ± 34.14	103.0 ± 29.79

Study locations

7 sites

Eunpyeong St. Mary's Hospital
Seoul, Eunpyeong-gu 03312, South Korea
Inje University Ilsan-Paik Hospital
Goyang-si, Gyeonggi-do 10380, South Korea
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do 13620, South Korea
Keimyung University Dongsan Medical Center
Daegu, Gyeongsangbuk-do 42601, South Korea
Ulsan University Hospital
Ulsan, Gyeongsangnam-do 44033, South Korea
Chonnam National University Hospital
Gwangju, Jeollanam-do 61469, South Korea
Kangbuk Samsung Hospital
Seoul, 03181, South Korea

References and documents

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 documents

Study protocol · Jun 27, 2024
Statistical analysis plan · Oct 31, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 9, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05761444
Lead sponsor: Organon and Co
Collaborators: IQVIA Pty Ltd
Responsible party: Sponsor
First posted: Mar 9, 2023
Start date: Jul 26, 2023
Primary completion: Sep 4, 2024
Completion: Oct 15, 2024
Results posted: Sep 9, 2025
Last update: Sep 9, 2025

Study contacts

WonYoung Lee

study director · Organon

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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