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

Organon

Status and phase: Completed; Phase 4

Conditions: Atherosclerotic Cardiovascular Disease

Treatments: Drug: Atozet 10/40 mg or 10/80 mg; Drug: Lipitor 40 mg or 80 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05761444

OG-KORATO-001

Details and patient eligibility

About

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.

Enrollment: 137 patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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137 participants in 2 patient groups

Eze/Ato: Ezetimibe/Atorvastatin

Experimental group

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.

Treatment:

Drug: Atozet 10/40 mg or 10/80 mg

Ato: Atorvastatin

Active Comparator group

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.

Treatment:

Drug: Lipitor 40 mg or 80 mg