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

Primary Purpose

Atherosclerotic Cardiovascular Disease

Status
Recruiting
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Atozet 10/40 mg or 10/80 mg
Lipitor 40 mg or 80 mg
Sponsored by
Organon and Co
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atherosclerotic Cardiovascular Disease focused on measuring Very high-risk patients' Atherosclerotic cardiovascular disease (ASCVD)

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: 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.

Sites / Locations

  • Inje University Ilsan-Paik HospitalRecruiting
  • Seoul National University Bundang Hospital
  • Kyungpook National University Hospital
  • Keimyung University Dongsan Medical Center
  • Ulsan University HospitalRecruiting
  • Chonnam National University HospitalRecruiting
  • Kangbuk Samsung Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Eze/Ato: Ezetimibe/Atorvastatin

Ato: Atorvastatin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
: 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
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
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.
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.

Full Information

First Posted
February 27, 2023
Last Updated
August 18, 2023
Sponsor
Organon and Co
Collaborators
Iqvia Pty Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05761444
Brief Title
Effectiveness and Safety Study of Early add-on of Ezetimibe With Atorvastatin in Very High-risk Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 26, 2023 (Actual)
Primary Completion Date
May 10, 2024 (Anticipated)
Study Completion Date
January 17, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Organon and Co
Collaborators
Iqvia Pty Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerotic Cardiovascular Disease
Keywords
Very high-risk patients' Atherosclerotic cardiovascular disease (ASCVD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
126 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Eze/Ato: Ezetimibe/Atorvastatin
Arm Type
Experimental
Arm Description
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.
Arm Title
Ato: Atorvastatin
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Atozet 10/40 mg or 10/80 mg
Intervention Description
Atozet 10/40 mg or 10/80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily
Intervention Type
Drug
Intervention Name(s)
Lipitor 40 mg or 80 mg
Intervention Description
Lipitor 40 mg or 80 mg Dosage Formulation: Tablet Dosing Instructions: oral. Take 1 tablet daily
Primary Outcome Measure Information:
Title
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
Description
All laboratory tests are performed in the local laboratory , percentage change in LDL-C from baseline to 6 weeks.
Time Frame
Week 6
Secondary Outcome Measure Information:
Title
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
Description
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
Time Frame
Week 12
Title
Proportion of patients achieving LDL-C goal of <70 mg/dL after 6 weeks and 12 weeks of treatment.
Description
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
Time Frame
Week 12
Title
: Percentage change in LDL-C from baseline to week 12
Description
All laboratory tests are performed in the local laboratory, Percentage change in LDL-C from baseline to week 12
Time Frame
Week 12
Title
Percentage change in HDL-C, non-HDL-C, triglycerides, and total cholesterol from baseline to week 6 and week 12
Description
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
Time Frame
Week 12
Title
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
Description
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.
Time Frame
Week 12
Title
Dropout rate due to TEAEs at 6 weeks and 12 weeks
Description
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.
Time Frame
Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
WonYoung Lee, MD
Phone
82 1577 8582
Email
won.young.lee@organon.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Minseol Jeon
Organizational Affiliation
Organon
Official's Role
Study Director
Facility Information:
Facility Name
Inje University Ilsan-Paik Hospital
City
Goyang
State/Province
Gyeonggi-do
ZIP/Postal Code
10380
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sung Uk Kwon
First Name & Middle Initial & Last Name & Degree
Sung Uk Kwon
Facility Name
Seoul National University Bundang Hospital
City
Seongnam-si
State/Province
Gyeonggi-do
ZIP/Postal Code
13620
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
In-Ho Chae
First Name & Middle Initial & Last Name & Degree
In-Ho Chae
Facility Name
Kyungpook National University Hospital
City
Daegu
State/Province
Gyeongsangbuk-do
ZIP/Postal Code
41944
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jang Hoon Lee
First Name & Middle Initial & Last Name & Degree
Jang Hoon Lee
Facility Name
Keimyung University Dongsan Medical Center
City
Daegu
State/Province
Gyeongsangbuk-do
ZIP/Postal Code
42601
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chang-Wook Nam
First Name & Middle Initial & Last Name & Degree
Chang-Wook Nam
Facility Name
Ulsan University Hospital
City
Ulsan
State/Province
Gyeongsangnam-do
ZIP/Postal Code
44033
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gyung Min Park
First Name & Middle Initial & Last Name & Degree
Gyung Min Park
Facility Name
Chonnam National University Hospital
City
Gwangju
State/Province
Jeollanam-do
ZIP/Postal Code
61469
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
YoungJoon Hong
First Name & Middle Initial & Last Name & Degree
YoungJoon Hong
Facility Name
Kangbuk Samsung Hospital
City
Seoul
ZIP/Postal Code
03181
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jong-Young Lee
First Name & Middle Initial & Last Name & Degree
Jong-Young Lee

12. IPD Sharing Statement

Learn more about this trial

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

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