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
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20

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
To evaluate the effectiveness of early add-on of ezetimibe with atorvastatin in very high-risk patients - Percentage change in LDL-C from baseline to week 6	Week 6	All laboratory tests are performed in the local laboratory , percentage change in LDL-C from baseline to 6 weeks.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients achieving LDL-C goal of <70 mg/dL after 6 weeks and 12 weeks of treatment.	Week 6, Week 12	All laboratory tests are performed in the local laboratory, Proportion of patients achieving LDL-C goal of \<70 mg/dL after 6 weeks and 12 weeks of treatment.
Percentage change in LDL-C from baseline to week 12.	Week 12	All laboratory tests are performed in the local laboratory, Percentage change in LDL-C from baseline to week 12.
Percentage change in HDL-C, non-HDL-C, triglycerides, and total cholesterol from baseline to week 6 and week 12.	Week 6, Week 12	All laboratory tests are performed in the local laboratory, Percentage change in HDL-C, non-HDL-C, from baseline to week 6 and week 12.
To evaluate the clinical effectiveness of early add-on of ezetimibe with atorvastatin in very high-risk patients Proportion of patients achieving LDL-C goal of <55 mg/dL after 6 weeks and 12 weeks of treatment.	Week 6, Week 12	All laboratory tests are performed in the local laboratory, Proportion of patients achieving LDL-C goal of \<55 mg/dL after 6 weeks and 12 weeks of treatment.
To evaluate the safety of early add-on of ezetimibe with atorvastatin in very high-risk patients - Treatment-emergent adverse events (TEAEs) at 6 weeks and 12 weeks.	Week 6, Week 12	The number and percentage of patients experiencing TEAEs, treatment-emergent serious adverse events (TESAE)s, Treatment-related adverse events (TRAEs) and TEAEs leading to the premature discontinuation of the study at 6 weeks and 12 weeks will be presented by treatment group and tested using Chi-square test or Fisher's exact test as appropriate. The difference in the percentages will be presented with its corresponding 95% CI and p-value.
Dropout rate due to TEAEs at 6 weeks and 12 weeks	Week 6, Week 12	The number and percentage of patients experiencing TEAEs, treatment-emergent serious adverse events (TESAE)s, Treatment-related adverse events (TRAEs) and TEAEs leading to the premature discontinuation of the study at 6 weeks and 12 weeks will be presented by treatment group and tested using Chi-square test or Fisher's exact test as appropriate. The difference in the percentages will be presented with its corresponding 95% CI and p-value.

Trial Locations

Locations (7)

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

Inje University Ilsan-Paik Hospital; 🇰🇷 Goyang, Gyeonggi-do, Korea, Republic of

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

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

Ulsan University Hospital; 🇰🇷 Ulsan, Gyeongsangnam-do, Korea, Republic of

Kangbuk Samsung Hospital; 🇰🇷 Seoul, Korea, Republic of

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