Verified May 2017 by Joo-Yong Hahn, Samsung Medical Center
Hanmi Pharm. Co., Ltd.
Information provided by (Responsible Party):
Joo-Yong Hahn, Samsung Medical Center
First received: May 24, 2017
Last updated: May 26, 2017
Last verified: May 2017
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.
|Coronary Artery Disease||Drug: Rosuvastatin 10 mg plus ezetimibe 10 mg orally once a day
Drug: Rosuvastatin 20 mg orally once a day
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Prospective, open label, two-arm, randomized controlled trial
Masking: Outcomes Assessor
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.
Primary Purpose: Treatment
|Official Title:||The Effect of Usual Dose Rosuvastatin Plue Ezetimibe Versus High-dose Rosuvastatin on Coronary Atherosclerotic Plaque: A Randomized Controlled Trial|
- 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
- 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
- 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
- Change in fibrous cap thickness by OCT(optical coherence tomography) [ Time Frame: 12 months after index CAG ]
In case that OCT is conducted
- Change in fractional flow reserve(FFR) [ Time Frame: 12 months after index CAG ]
- Change in coronary flow reserve(CFR) [ Time Frame: 12 months after index CAG ]
- Change in index of microcirculatory resistance(IMR) [ Time Frame: 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
- 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.
- 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
- Change in fasting glucose [ Time Frame: 6 and 12 months after index CAG ]
For risk of developing diabetes mellitus by statin therapy
- Change in hemoglobin A1c [ Time Frame: 6 and 12 months after index CAG ]
For risk of developing diabetes mellitus by statin therapy
- 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.
- Change in high-sensitivity C-reactive protein(hs-CRP) [ Time Frame: 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 ]
- Creatine kinase(CK) elevation > 10 times upper limit of normal(ULN)
- CK elevation > 10 times ULN on two consecutive visits
- Hepatic transaminases > 3 times ULN
- Hepatic transaminases > 3 times ULN on two consecutive visits
- 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.
|Anticipated Study Start Date:||June 1, 2017|
|Estimated Study Completion Date:||December 31, 2023|
|Estimated Primary Completion Date:||December 31, 2021 (Final data collection date for primary outcome measure)|
|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 Name: 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 Name: Crestor tablet 10 mg
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, we 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.
|Ages Eligible for Study:||18 Years and older (Adult, Senior)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Please refer to this study by its ClinicalTrials.gov identifier: NCT03169985
|Samsung Medical Center|
|Seoul, Korea, Republic of, 06351|
Samsung Medical Center
Hanmi Pharm. Co., Ltd.
|Study Chair:||Joo-Yong Hahn, MD, PhD||Samsung Medical Center|
|Responsible Party:||Joo-Yong Hahn, Professor, Samsung Medical Center|
|ClinicalTrials.gov Identifier:||NCT03169985 History of Changes|
|Other Study ID Numbers:||Rosuzet-IVUS16453143|
|Study First Received:||May 24, 2017|
|Last Updated:||May 26, 2017|
|Individual Participant Data|
|Plan to Share IPD:||Yes|
|Plan Description:||After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked.|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Keywords provided by Joo-Yong Hahn, Samsung Medical Center:
Additional relevant MeSH terms:
|Coronary Artery Disease
Arterial Occlusive Diseases
Pathological Conditions, Anatomical
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
ClinicalTrials.gov processed this record on May 30, 2017