Efficacy and Safety of Combination Therapy of Moderate-intensity Statin and Ezetimibe Compared to High-intensity Statin

Efficacy and Safety of Combination Therapy of Moderate-intensity Statin and Ezetimibe Compared to High-intensity Statin: Study Protocol for a Randomized Controlled Trial

This study is a multicenter, randomized, open-label, parallel, phase IV trial.

The purpose of this study efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Drug: Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin

Detailed Description

The study is planned to include 272 patients with a clinical atherosclerotic cardiovascular disease requiring optimal statin therapy.

After enrollment, subjects are randomized into two groups in a 1:1 manner. The combination therapy group will receive a single-pill combination of rosuvastatin 10 mg and ezetimibe 10 mg once daily.

The subjects in the intensive statin group will receive rosuvastatin 20 mg once daily.

Subjects will visit at weeks 12 and 24 to identify medication adherence and clinical side effects.

The primary endpoint of this study is a % change of low-density lipoprotein cholesterol at 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 06511
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged between 19 and 75 years

2. Presence of atherosclerotic cardiovascular disease Coronary artery disease

   • History of acute coronary syndrome
   • Stable or unstable angina
   • History of coronary revascularization Stroke or TIA Peripheral arterial disease, history of peripheral arterial revascularization
3. Patients who have been taking lipid-lowering agents (statin or ezetimibe) for ≥4 weeks at the time of randomization
4. Patients who gave informed consent

Exclusion Criteria:

1. Patients who have used lipid-lowering agents other than statin or ezetimibe within the last 3 months
2. A serum triglyceride on fasting >400 mg/dL
3. A history of muscular symptoms or rhabdomyolysis due to the use of statin
4. Hypersensitivity to rosuvastatin or ezetimibe
5. Labeled contraindications to rosuvastatin or rosuvastatin Severe renal impairment (CrCl <30 mL/min by Cockcroft-Gault formula or estimated GFR <30 mL/min / 1.73 m2 by MDRD equation) ALT, AST ≥3 × ULN or active liver disease CPK ≥3 × ULN
6. Enrollment of other clinical trials within 30 days
7. Any other issues that the treating physician assumes ineligible for participation in the trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: combination therapy group; The combination therapy group will receive a single-pill combination of rosuvastatin 10 mg and ezetimibe 10 mg once daily.	Drug: Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin; This study is a multicenter, randomized, open-label, parallel, phase IV trial. The study is planned to include 272 patients with clinical ASCVD requiring optimal statin therapy. After enrollment, subjects are randomized into two groups in a 1:1 manner. patients in combination therapy group(rosuvastation 10mg and ezetimibe 10mg daily) will be provided a fixed-dose single pill comibation and patients in the intensive statin group will receive rosuvastatin 20mg daily.
Other: intensive statin group; The subjects in the intensive statin group will receive rosuvastatin 20 mg once daily.	Drug: Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin; This study is a multicenter, randomized, open-label, parallel, phase IV trial. The study is planned to include 272 patients with clinical ASCVD requiring optimal statin therapy. After enrollment, subjects are randomized into two groups in a 1:1 manner. patients in combination therapy group(rosuvastation 10mg and ezetimibe 10mg daily) will be provided a fixed-dose single pill comibation and patients in the intensive statin group will receive rosuvastatin 20mg daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% change of low-density lipoprotein cholesterol	%change of LDL-C = (LDL-C at 12 weeks) - (LDL-C at baseline)/LDL-C at baseline * 100	at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% change of serum cholesterol level	total cholesterol, LDL, HDL cholesterol, triglyceride (mg/dL)	at 12 and 24 weeks
% change of high-sensitivity C-reactive protein	hs-CRP(mg/dL)	at 12 and 24 weeks
% change of fasting glucose	fasting plasma glucose(mg/dL)	at 12 and 24 weeks
% change of homeostatic model assessment for insulin resistance(HOMA-IR)	HOMA-IR = glucose * insulin / 405(glucose mg/dL , insulin uIU/mL)	at 12 and 24 weeks
proportion of participant with statin-associated muscle symptoms	occurrence of statin-associated muscle symptoms	at 12 and 24 weeks
proportion of participant with creatinine phosphokinase elevation	proportion of CPK elevation ≥4 or ≥10 upper normal of limit	at 12 and 24 weeks
proportion of participant with liver function test abnormality	proportion of AST/ALT elevation ≥4 or ≥10 upper normal of limit	at 12 and 24 weeks
proportion of participant with major adverse cardiovascular and cerebrovascular events(MACCE)	MACCE defined as a composite of the followings : cardiovascular death, acute myocardial infarction, unstable angina, stroke	at 12 and 24 weeks

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Yuhan Corporation

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Actual): June 15, 2019
• Study Completion (Actual): September 17, 2019

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: September 3, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 19, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Other Study ID Numbers: YMC033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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