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

Phase 4

Completed

• Conditions: Atherosclerotic Cardiovascular Disease
• Interventions: Drug: Atozet 10/40 mg or 10/80 mg; Drug: Lipitor 40 mg or 80 mg

• Registration Number: NCT05761444
• Lead Sponsor: Organon and Co

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-27
• Study First Submitted QC: 2023-03-08
• Study First Posted: 2023-03-09
• Study Start: 2023-07-26
• Primary Completion: 2024-09-04
• Status Verified: 2024-10
• Study Completion: 2024-10-15
• Results First Submitted: 2025-08-20
• Results First Submitted QC: 2025-08-20
• Last Update Submitted: 2025-08-20
• Results First Posted: 2025-09-09
• Last Update Posted: 2025-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 137

Inclusion Criteria

1. Patients who are ≥ 30 years old.

2. 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).

3. 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).

4. Patients with LDL-C levels ≥ 70 mg/dL

5. Patients who are willing to maintain TLC throughout the study.

6. Patients who are willing to provide written informed consent prior to study enrollment.

Exclusion Criteria

1. Patients with hypersensitivity to ezetimibe, atorvastatin or any of its inactive ingredients.
2. 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)).
3. Patients who have predisposing conditions with muscle disease (i.e., rhabdomyolysis or myopathy) or neuromuscular disease.
4. Patients with myasthenia gravis.
5. Female patients who are pregnant or have a potential to be pregnant and nursing.
6. Patients who are taking glecaprevir and pibrentasvir.
7. Patients with hereditary problems of galactose intolerance, lapp lactase deficiency, or of glucose-galactose malabsorption.
8. Patients with disease known to influence serum lipids or lipoproteins excluding dyslipidemia.
9. Patients with a history of cancer within 5 years.
10. Patients whose life expectancy is less than 6 months due to their medical conditions.
11. Patients with any condition or situation that might pose a risk to the participant or interfere with participation in the study.
12. Patients who have received any investigational medicine within 12 weeks of written informed consent or are going to receive during the clinical trial period.
13. Patients who are judged to be difficult to conduct clinical trials according to the judgment of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Eze/Ato: Ezetimibe/Atorvastatin	Atozet 10/40 mg or 10/80 mg	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.
Ato: Atorvastatin	Lipitor 40 mg or 80 mg	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.

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 6	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Low-Density Lipoprotein Cholesterol Goal of <55 mg/dL at Weeks 6 and 12	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.
Percentage of Participants Who Achieved Low-Density Lipoprotein Cholesterol Goal of <70 mg/dL at Weeks 6 and 12	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.
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12	Baseline (Day 1) and 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.
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	Baseline (Day 1) and 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) at Weeks 6 and 12	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	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.
Number of Participants With Treatment-Emergent Adverse Event Leading to the Premature Discontinuation of the Study	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	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.

Trial Locations

Locations (7)

Eunpyeong St. Mary's Hospital; 🇰🇷 Seoul, Eunpyeong-gu, South Korea

Inje University Ilsan-Paik Hospital; 🇰🇷 Goyang-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-do, South Korea

Keimyung University Dongsan Medical Center; 🇰🇷 Daegu, Gyeongsangbuk-do, South Korea

Ulsan University Hospital; 🇰🇷 Ulsan, Gyeongsangnam-do, South Korea

Chonnam National University Hospital; 🇰🇷 Gwangju, Jeollanam-do, South Korea

Kangbuk Samsung Hospital; 🇰🇷 Seoul, South Korea