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

NCT03169985 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: Rosuzet-IVUS16453143
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Disease

Keywords

Rosuvastatin; Ezetimibe; Atherosclerotic plaque; Intravascular ultrasound

Outcome Measures

Primary Outcomes (1)

• Change in percent atheroma volume(PAV) in non-culprit lesions

  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 Outcomes (14)

• Change in normalized TAV in non-culprit lesions

  12 months after index CAG

• Change in indexed TAV

  12 months after index CAG

• Change in fibrous cap thickness by OCT(optical coherence tomography)

  12 months after index CAG

• Change in fractional flow reserve(FFR)

  12 months after index CAG

• Change in coronary flow reserve(CFR)

  12 months after index CAG

Study Arms (2)

Rosuvastatin plus ezetimibe arm

ACTIVE COMPARATOR

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

High-dose rosuvastatin monotherapy arm

ACTIVE COMPARATOR

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

Interventions

Rosuvastatin 10 mg plus ezetimibe 10 mg orally once a day DRUG

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.

Also known as: Rosuzet tablet 10/10 mg

Rosuvastatin plus ezetimibe arm

Rosuvastatin 20 mg orally once a day DRUG

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.

Also known as: Crestor tablet 20 mg

High-dose rosuvastatin monotherapy arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Samsung Medical Center: lead
• Hanmi Pharmaceutical co., ltd.: collaborator

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

Location

MeSH Terms

Conditions

Coronary Artery Disease; Plaque, Atherosclerotic

Interventions

Rosuvastatin Calcium; Ezetimibe

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azetidines; Azetines

Study Officials

• Joo-Yong Hahn, MD, PhD

  Samsung Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The obtained intravascular ultrasound(IVUS) data will be stored through the storage device in the core lab of Heart Center of Heart Vascular Stroke Institute in Samsung Medical Center, and the treatment group to which the patient belongs would not be known. Subsequent baseline and follow-up IVUS data will be analyzed together by independent experts without knowledge of the patient's treatment group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, open label, two-arm, randomized controlled trial

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: May 30, 2017
• Study Start: July 12, 2017
• Primary Completion (Estimated): January 28, 2027
• Study Completion (Estimated): January 28, 2027
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

KR (1)