Clinical trial NCT05761444: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atherosclerotic Cardiovascular Disease
Keywords: Very high-risk patients' Atherosclerotic cardiovascular disease (ASCVD)
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2023-03-09
Enrollment: 137
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Week 6
Secondary outcomes:
measure: 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.
timeFrame: Week 6, Week 12
measure: Proportion of patients achieving LDL-C goal of <70 mg/dL after 6 weeks and 12 weeks of treatment.
timeFrame: Week 6, Week 12
measure: Percentage change in LDL-C from baseline to week 12.
timeFrame: Week 12
measure: Percentage change in HDL-C, non-HDL-C, triglycerides, and total cholesterol from baseline to week 6 and week 12.
timeFrame: Week 6, Week 12
measure: 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.
timeFrame: Week 6, Week 12
measure: Dropout rate due to TEAEs at 6 weeks and 12 weeks
timeFrame: Week 6, Week 12
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Eunpyeong St. Mary's Hospital
state: Eunpyeong-gu
city: Goyang
country: Korea, Republic of
facility: Inje University Ilsan-Paik Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
state: Gyeongsangbuk-do
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
state: Gyeongsangnam-do
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
state: Jeollanam-do
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
Study officials:
affiliation: Organon
name: WonYoung Lee
role: STUDY_DIRECTOR
References: