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

Atherosclerotic Cardiovascular Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05761444
• Other study ID #: OG-KORATO-001
• Status: Recruiting
• Phase: Phase 4
• Start date: July 26, 2023
• Est. completion date: January 17, 2025

Study information

• Verified date: February 2024
• Source: Organon and Co
• Contact: WonYoung Lee, MD
• Phone: 82 1577 8582
• Email: won.young.lee[@]organon.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: January 17, 2025
• Est. primary completion date: November 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• Atozet 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
• Lipitor 40 mg or 80 mg
Lipitor 40 mg or 80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily

Locations

Country	Name	City	State
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu	Gyeongsangbuk-do
Korea, Republic of	Kyungpook National University Hospital	Daegu	Gyeongsangbuk-do
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	Eunpyeong St. Mary's Hospital	Seoul	Eunpyeong-gu
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan	Gyeongsangnam-do

Sponsors (2)

Lead Sponsor	Collaborator
Organon and Co	Iqvia Pty Ltd

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	All laboratory tests are performed in the local laboratory , percentage change in LDL-C from baseline to 6 weeks.	Week 6
Secondary	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	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	Week 12
Secondary	Proportion of patients achieving LDL-C goal of <70 mg/dL after 6 weeks and 12 weeks of treatment.	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	Week 12
Secondary	: Percentage change in LDL-C from baseline to week 12	All laboratory tests are performed in the local laboratory, Percentage change in LDL-C from baseline to week 12	Week 12
Secondary	Percentage change in HDL-C, non-HDL-C, triglycerides, and total cholesterol from baseline to week 6 and 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	Week 12
Secondary	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	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.	Week 12
Secondary	Dropout rate due to TEAEs at 6 weeks and 12 weeks	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.	Week 12