Randomized Controlled Trial of Moderate-Intensity Rosuvastatin With Ezetimibe Combination Therapy Versus High-Intensity Rosuvastatin on Progression of Coronary Atherosclerotic Plaque (Rosuzet-IVUS)

July 13, 2025 updated by: Joo-Yong Hahn, Samsung Medical Center

The Effect of Moderate-intensity Rosuvastatin Plus Ezetimibe Versus High-intensity Rosuvastatin on Coronary Atherosclerotic Plaque by Intravascular Ultrasound (ROSUZET-IVUS Trial)

The aim of this prospective, open-label, randomized, single center study is to compare the effect of usual dose rosuvastatin plus ezetimibe and high-dose rosuvastatin on modifying atherosclerotic plaque.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

High-intensity statin therapy have shown improved clinical outcomes compared to placebo or moderate-intensity statin therapy. Based on these results, 2013 American College of Cardiology/American Heart Association(ACC/AHA) guideline on treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults recommended high-intensity statin therapy to patient with coronary artery disease for secondary prevention. However, high-intensity statin therapy was known to increase risk of diabetes mellitus and complication such as hepatotoxicity and myalgia. An alternative to high-intensity statin therapy is reducing the dose of statin and using drug that can improve blood cholesterol level by a different mechanism than statin. Ezetimibe acts on Niemann-Pick C1-like protein then inhibits cholesterol absorption in the intestine, which can reduce low-density lipoprotein(LDL) cholesterol more effectively when administered with statin. In IMPROVE-IT study, simvastatin plus ezetimibe decreased ischemic events more than simvastatin alone in patients with acute coronary syndrome. Although this study could confirm the additional effect of ezetimibe by using the same amount of simvastatin in both groups, it could not compare the effect of statin plus ezetimibe and high dose statin monotherapy. Moreover, there were few data on the efficacy of ezetimibe added to rosuvastatin which is one of the effective statin recommended by various guidelines. One study reported that rosuvastatin 2.5 mg plus ezetimibe 10 mg was superior to rosuvastatin 5 mg monotherapy in reducing LDL cholesterol. Another study reported that adding rosuvastatin 5 mg to ezetimibe 10 mg was more effective than rosuvastatin 5 mg alone in reducing coronary atherosclerotic lesions as measured by intravascular ultrasound. However, the previous studies did not compare the efficacy of combination therapy of usual dose rosuvastatin and ezetimibe to high-dose statin monotherapy. Therefore, investigators aimed to compare the effect of rosuvastatin 10 mg plus ezetimibe 10 mg to rosuvastatin 20 mg alone on the reduction of coronary atherosclerosis in patient with coronary artery disease. If this study shows that the combination of usual dose rosuvastatin and ezetimibe is not inferior to high dose rosuvastatin monotherapy in anti-atherosclerotic effect and safety, it would provide a basis for effective and safe cholesterol treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
280

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Joo-Yong Hahn, MD, PhD
  • Phone Number: 82-2-3410-6653
  • Email: ichjy1@gmail.com

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subject must be at least 19 years of age
  • Subject with suspected ischemic heart disease undergoing coronary angiography and have intermediate coronary artery stenosis (30-70% by visual estimation) whose revascularization was deferred based on invasive physiologic assessment using fractional flow reserve (>0.80) or intravascular ultrasound (minimum lumen area> 4mm2)
  • Subject can verbally confirm understandings of risks, benefits and treatment alternatives of receiving statin or ezetimibe and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.

Exclusion Criteria:

  • Subject has calculated creatinine clearance <30 mL/min or dialysis within 30 days.
  • Subject has active liver disease or persistent unexplained serum transaminase elevations (x2 x upper limit of normal [ULN]).
  • Subject requires the following concomitant medications: cyclosporine, danazol, niacin, fibrates as concomitant medications
  • Subject requires any of the potent CYP3A4 inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, and telithromycin, HIV protease inhibitors, nefazodone, probucol, resins, and any investigational drugs.
  • Subject has an allergy/sensitivity to any statin, ezetimibe, and/or their excipients.
  • Subject with history of myopathy or family history of myopathy
  • Untreated hypothyroidism
  • Subject has a history of alcohol and/or drug abuse.
  • Subject is a pregnant or lactating woman, or woman intending to become pregnant.
  • Non-cardiac co-morbid conditions are present with life expectancy <2 year or that may result in protocol non-compliance (per site investigator's medical judgment).

  • Unwillingness or inability to comply with the procedures described in this protocol.

    • Eligible patients will be randomly assigned to treatment arms, stratified by diagnosis on admission(acute coronary syndrome or stable ischemic heart disease) and presence of chronic statin use (more than one month)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Rosuvastatin plus ezetimibe arm
In patients who have moderate stenosis(30-70%) in coronary artery and deferred to medical treatment by intracoronary physiologic or radiologic test, this arm will be received rosuvastatin 10 mg plus ezetimibe 10 mg qd during 12 months after randomization.
Drug: Rosuvastatin 10 mg plus ezetimibe 10 mg orally once a day
After the initial 12 months, randomized intervention will be stopped and then this arm will be received either usual dose rosuvastatin plus ezetimibe or high-dose rosuvastatin during the next 24 months by clinical judgement.
Other Names:
  • Rosuzet tablet 10/10 mg
Active Comparator: High-dose rosuvastatin monotherapy arm
In patients who have moderate stenosis(30-70%) in coronary artery and deferred to medical treatment by intracoronary physiologic or radiologic test, this arm will be received rosuvastatin 20 mg qd during 12 months after randomization.
Drug: Rosuvastatin 20 mg orally once a day
After the initial 12 months, randomized intervention will be stopped and then this arm will be received either usual dose rosuvastatin plus ezetimibe or high-dose rosuvastatin during the next 24 months based by clinical judgement.
Other Names:
  • Crestor tablet 20 mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in percent atheroma volume(PAV) in non-culprit lesions
Time Frame: 12 months after index coronary angiography(CAG)

PAV is calculated as the percentage of the sum of external elastic membrane(EEM) cross sectional areas(CSA) occupied by total atheroma volume(TAV). TAV was determined by summation of the plaque area, defined as the difference between EEM and lumen CSA, for all evaluable images. These values could be expressed as follows:

TAV = ∑(EEM CSA - lumen CSA), PAV = 100 X ∑(EEM CSA - lumen CSA) / ∑EEM CSA
12 months after index coronary angiography(CAG)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in normalized TAV in non-culprit lesions
Time Frame: 12 months after index CAG

The TAV is normalized to the length corresponding to the median number of comparable slices for each treatment group in view of the variability in the length of pullback analyzed between subjects. This value could be expressed as follows:

normalized TAV = [∑(EEM CSA - lumen CSA) / number of images in pullback] X median number of images in cohort
12 months after index CAG
Change in indexed TAV
Time Frame: 12 months after index CAG

Indexed TAV is calculated as TAV divided by the length of plaque in each subject. This value could be expressed as follows:

Indexed TAV = ∑(EEM CSA - lumen CSA) / plaque length
12 months after index CAG
Change in fibrous cap thickness by OCT(optical coherence tomography)
Time Frame: 12 months after index CAG
In case that OCT is conducted
12 months after index CAG
Change in fractional flow reserve(FFR)
Time Frame: 12 months after index CAG
Physiologic index
12 months after index CAG
Change in coronary flow reserve(CFR)
Time Frame: 12 months after index CAG
Physiologic index
12 months after index CAG
Change in index of microcirculatory resistance(IMR)
Time Frame: 12 months after index CAG
Physiologic index
12 months after index CAG
Change in TAV in coronary computed tomography(CT) angiography
Time Frame: 24 months after index CAG
TAV which is measured in CT angiography
24 months after index CAG
Major adverse cardiovascular events(MACE)
Time Frame: 12, 24 and 36 months after index CAG
MACE is defined as a composite of death, myocardial infarction, stroke and revascularization.
12, 24 and 36 months after index CAG
Change in homeostatic model assessment(HOMA) index
Time Frame: 6 months after index CAG

HOMA index is a method used to quantify insulin resistance. This values could be calculated with fasting plasma glucose and insulin, as follows:

HOMA index = glucose X insulin (mg/dL) / 405
6 months after index CAG
Change in fasting glucose
Time Frame: 6 and 12 months after index CAG
For risk of developing diabetes mellitus by statin therapy
6 and 12 months after index CAG
Change in hemoglobin A1c
Time Frame: 6 and 12 months after index CAG
For risk of developing diabetes mellitus by statin therapy
6 and 12 months after index CAG
Change in lipid profile
Time Frame: 1, 6 and 12 months after index CAG
Fasting plasma triglyceride(TG), high-density lipoprotein(HDL), LDL and total cholesterol. These items will be compared separately, and described as a group of lipid profile.
1, 6 and 12 months after index CAG
Change in high-sensitivity C-reactive protein(hs-CRP)
Time Frame: 1 and 12 months after index CAG
hs-CRP
1 and 12 months after index CAG
Safety endpoint: Number of participants with abnormal laboratory values and adverse events
Time Frame: 1 and 12 months after index CAG
  1. Creatine kinase(CK) elevation > 10 times upper limit of normal(ULN)
  2. CK elevation > 10 times ULN on two consecutive visits
  3. Hepatic transaminases > 3 times ULN
  4. Hepatic transaminases > 3 times ULN on two consecutive visits
  5. Document reason for discontinuation of study medication

These items will be described together as a group of safety endpoint, such as number of participants with abnormal laboratory values and adverse events.
1 and 12 months after index CAG

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Samsung Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hanmi Pharmaceutical co., ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Joo-Yong Hahn, MD, PhD, Samsung Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 12, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 28, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 28, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 24, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 30, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 16, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 13, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Rosuzet-IVUS16453143

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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