Compare the Efficacy and Safety of Rosuvastatin/Ezetimibe Combination Therapy Versus Rosuvastatin Monotherapy in Korean Patients With Left Ventricular Diastolic Dysfunction and Hyperlipidemia

A Randomized, Single-center, Open, Parallel, Phase 4 Study to Compare the Efficacy and Safety of Rosuvastatin/Ezetimibe Combination Therapy Versus Rosuvastatin Monotherapy in Korean Patients With Left Ventricular Diastolic Dysfunction and Hyperlipidemia

preserved left ventricular ejection fraction (LVEF ≥ 50%) and are accompanied by dyslipidemia (LDL ≥ 100 mg / dl) will be enrolled.

Only patients who do not meet the exclusion criteria should be enrolled in the study.

Once the patient is selected, the patient is informed of the study and receives the consent form.

Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly assigned in a 1: 1 dose of rosuvastatin/ezetimibe 10/10mg once daily or rosuvastatin 20 mg once daily. Patients who previously used statins have a wash-out period of 4 weeks or more.

Patients will visit outpatient clinic at 12 weeks and 24 weeks after initiation of treatment. Physical examination, blood test, and 6 minute working test will be performed. For fasting blood tests, patients visit on an empty stomach. Drug adverse events and changes in vital signs or body weight will be checked.

After 48 weeks of treatment, the patients will visit outpatient clinic for efficacy evaluation; physical examination, blood test, transthoracic echocardiography, cardiopulmonary exercise test, central blood pressure, and pulse wave velocity. Drug adverse events and medication compliance will be checked.

The primary endpoint is change of low-density lipoprotein cholesterol and secondary endpoint is improvement of diastolic dysfunction, VAC index, peak VO2, distance of 6 minute working test, and clinical outcomes including death, readmission rate.

Study Overview

• Status: Recruiting
• Conditions: Hyperlipidemias; Left Ventricular Diastolic Dysfunction
• Intervention / Treatment: Drug: Rosuvastatin 20; Drug: Rosuvamibe 10/10

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Geu-Ru Hong; Phone Number: 82-2-2228-8443; Email: grhong@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Yonsei Severance Hospital
    • Contact: Geu-Ru Hong; Phone Number: 82-2-2228-8443; Email: grhong@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants who have left ventricular diastolic dysfunction (relaxation abnormality, pseudonormalization, restrictive pattern) with preserved left ventricular systolic function (left ventricular ejection fraction ≥ 50%)
2. Adult participants (≥ 20 years old) who have dyslipidemia and need treatment
3. Patients who understand the information about the trial and voluntarily agree to participate in the trial

Exclusion Criteria:

1. Baseline fasting low-density lipoprotein cholesterol ≤ 70 mg/dL
2. Baseline fasting triglyceride ≥ 400 mg/dL
3. Baseline fasting total cholesterol ≥ 300 mg/dL
4. Participants who have structural heart disease
5. Participants who have prior acute coronary syndrome or cerebrovascular attack within 3 months.
6. Renal dysfunction (estimated glomerular filtration rate < 30mL/min/1.73m2)
7. Creatinine phosphokinase elevations greater than three times the upper limit of normal
8. Aspartate or alanine aminotransferase elevations greater than three times the upper limit of normal
9. Previous history of rhabdomyolysis
10. Females who are pregnant or breastfeeding or have a plan for pregnancy
11. Life expectancy less than a year.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rosuvastatin 20mg (Group 1)	Drug: Rosuvastatin 20; Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly enrolled in a 1: 1 dose of Rosuvastatin 20mg Monotherapy.
Experimental: Rosuvamibe 10/10mg (Group 2)	Drug: Rosuvamibe 10/10; Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly enrolled in a 1: 1 dose of rosuvastatin10mg/ezetimibe 10mg combination Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum level of low-density lipoprotein cholesterol	Compare the evaluation low-density lipoprotein cholesterol changes in Rosuvastatin/Ezetimibe Combination Therapy versus Rosuvastatin Monotherapy	24 weeks
Change in serum level of low-density lipoprotein cholesterol	Compare the evaluation low-density lipoprotein cholesterol changes in Rosuvastatin/Ezetimibe Combination Therapy versus Rosuvastatin Monotherapy	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement of diastolic dysfunction	48 weeks
Improvement of ventriculoarterial coupling index	48 weeks
Improvement of peak VO2	48 weeks
Improvement of 6 minute walking test combination therapy and monotherapy	48 weeks
Clinical outcomes including death rate	48 weeks
Clinical outcomes including readmission rate	48 weeks

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 13, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Ventricular Dysfunction; Hyperlipidemias; Hyperlipoproteinemias; Ventricular Dysfunction, Left; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: 4-2019-1125

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