The Effect of Moderate-intensity Rosuvastatin Plus Ezetimibe Versus High-intensity Rosuvastatin on Coronary Atherosclerotic Plaque by Intravascular Ultrasound (ROSUZET-IVUS Trial)
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 280
- 试验地点
- 1
- 主要终点
- Change in percent atheroma volume(PAV) in non-culprit lesions
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: Rosuvastatin 10 mg plus ezetimibe 10 mg orally once a day (Drug)
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.
干预措施: Rosuvastatin 20 mg orally once a day (Drug)
结局指标
主要结局
Change in percent atheroma volume(PAV) in non-culprit lesions
时间窗: 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
次要结局
- Change in index of microcirculatory resistance(IMR)(12 months after index CAG)
- Change in homeostatic model assessment(HOMA) index(6 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 normalized TAV in non-culprit lesions(12 months after index CAG)
- Change in indexed TAV(12 months after index CAG)
- Change in fasting glucose(6 and 12 months after index CAG)
- Change in TAV in coronary computed tomography(CT) angiography(24 months after index CAG)
- Change in lipid profile(1, 6 and 12 months after index CAG)
- Change in coronary flow reserve(CFR)(12 months after index CAG)
- Major adverse cardiovascular events(MACE)(12, 24 and 36 months after index CAG)
- Change in hemoglobin A1c(6 and 12 months after index CAG)
- Change in high-sensitivity C-reactive protein(hs-CRP)(1 and 12 months after index CAG)
- Safety endpoint: Number of participants with abnormal laboratory values and adverse events(1 and 12 months after index CAG)
研究者
Joo-Yong Hahn
Professor
Samsung Medical Center