Effects of Pitavastatin or Combination of Pitavastatin and Ezetimibe on Glucose Metabolism Compared to AtoRvastatin in atheroscLerotic Cardiovascular Disease Patients With Metabolic Syndrome: The EZ-PEARL Randomized Trial

The purpose of this study was to investigate the effect of pitavastatin or pitavastatin and ezetimibe combination therapy on glucose metabolism compared to atorvastatin in patients with atherosclerotic cardiovascular disease with metabolic syndrome.

Study Overview

• Status: Recruiting
• Conditions: Dyslipidemias; Atherosclerotic Cardiovascular Disease
• Intervention / Treatment: Drug: Pitavastatin; Drug: Pitavastatin plus Ezetemibe; Drug: Atorvastatin

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Byeong-Keuk Kim; Phone Number: 82-2-2228-8465; Email: KIMBK@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Yonsei University Health System, Severance Hospital
    • Contact: Byeong-Keuk Kim; Phone Number: 82-2-2228-8465; Email: KIMBK@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with dyslipidemia
2. Patient with diagnosis of clinical atherosclerotic cardiovascular disease (acute coronary syndrome, history of myocardial infarction, stable or unstable angina, history of coronary artery reperfusion, stroke or transient stroke, history of peripheral arterial disease or peripheral arterial reperfusion)
3. Patients with metabolic syndrome but without diabetes

Exclusion Criteria:

1. Diagnosis of clinical atherosclerotic cardiovascular disease within 1 year
2. Acute liver disease or persistent unexplained serum AST or ALT three times the upper limit of normal
3. Allergy or hypersensitivity to statins or ezetimibe
4. Solid organ transplant recipients
5. History of side effects requiring discontinuation of statin administration
6. Pregnant women, potentially pregnant or lactating women
7. Life expectancy less than 3 years
8. If it is judged that follow-up for more than 1 year is not possible
9. If the patient is unable to understand or read the consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group P; Pitavastatin 4mg group	Drug: Pitavastatin; Pitavastatin 4 mg will be given.
Experimental: Group PE; Pitavastatin 4 mg Ezetimibe 10 mg combined administration group	Drug: Pitavastatin plus Ezetemibe; Pitvastatin 4 mg plus ezetemibe 10 mg will be given.
Active Comparator: Group A; Atorvastatin 40 mg administration group	Drug: Atorvastatin; Atorvastatin 40 mg will be given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change form baseline homeostatic model assessment for insulin resistance (HOMA-IR) at 24 weeks	Changes of homeostatic model assessment for insulin resistance (HOMA-IR) form baseline to 24 weeks will be compared among the three groups.	At 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of fasting glucose ≥100 mg/dL	At 24 weeks
Proportion of HbA1C ≥6.5%	At 24 weeks
Proportion of new-onset diabetes mellitus	At 24 weeks
Changes of HOMA-β at 24 weeks	At 24 weeks
Changes of fasting glucose at 24 weeks	At 24 weeks
Changes of insulin at 24 weeks	At 24 weeks
Changes of HbA1c at 24 weeks	At 24 weeks
Changes of triglyceride at 24 weeks	At 24 weeks
LDL-cholesterol change at 24 weeks	At 24 weeks
HDL-cholesterol change at 24 weeks	At 24 weeks

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Byeong-Keuk Kim, Severance Cardiovascular Hospital, Yonsei University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 29, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Insulin Resistance; Hyperinsulinism; Lipid Metabolism Disorders; Cardiovascular Diseases; Metabolic Syndrome; Dyslipidemias; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Pitavastatin
• Other Study ID Numbers: 4-2022-1325

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No