A Randomized, Double-blind Study of Effect of Fimasartan for Modification of Atheroma Vulnerability in DEFERred Coronary Disease
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 186
- 试验地点
- 3
- 主要终点
- Change in percent necrotic core (NC) volume of plaque by VH (Virtual Histology) in the "target segment" (within deferred vessel)
研究概览
简要总结
- Fimasartan will be more beneficial in stabilizing the plaque vulnerability compared to control group in deferred coronary lesions.
- Fimasartan will be more beneficial in reducing total plaque volume compared to control group in deferred coronary lesions.
- Fimasartan will be more beneficial in reducing functional impairment of stenotic lesions (assessed by FFR:Fractional Flow Reserve) in deferred coronary lesions.
详细描述
Prospective, double-blind, randomized clinical study with enrollment of patients over at least 18 years of age who require coronary angiography for a clinical indication with hypertension defined as systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg. Inclusion requires at least one deferred coronary lesion with 1) visually-estimated angiographic %diameter stenosis 20-50% or 2) %diameter stenosis >50% without any evidence of inducible ischemia. The target vessel for IVUS interrogation must not have undergone angioplasty (deferred lesion) nor have more than 50% luminal narrowing throughout a target segment. Patients meeting inclusion criteria without any exclusion criteria will be randomized 1:1 (Fimasartan 60-120 mg vs placebo). All subjects will be followed up at 1 year for serial VH-IVUS and conventional IVUS evaluation. Also, OCT sub-study will be performed in selected patients with lesions at least 20 mm distally located from coronary ostium. All patients will be blindly assigned to control and Fimasartan once daily as 1:1 ratio and are prescribed for 1year.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hypertensive patients (systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg) or medically treated hypertension with normal blood pressure who undergo coronary angiography with clinical indications
- •18 < Age < 85
- •Patient who has received informed consent
- •at least one deferred coronary lesion with 1) visually-estimated angiographic %diameter stenosis 20-50% or 2) %diameter stenosis >50% without any evidence of inducible ischemia (FFR ≥ 0.8 or negative perfusion defect on thallium scan or negative treadmill test)
排除标准
- •Planned cardiac surgery (e.g., CABG, valve repair or replacement, or aneurysmectomy) or planned major non-cardiac surgery within the study period
- •Planned performance of PCI or CABG in the target vessel or its branches containing the index
- •Evidence of congestive heart failure, or left ventricular ejection fraction < 40%
- •Stroke or resuscitated sudden death in the past 6 months
- •Chronic disease requiring treatment with oral, intravenous, or intra-articular corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible)
- •A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer
- •Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study
- •Significant renal disease manifested by serum creatinine > 1.5 mg/dL
- •Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal)
- •Active hepatitis B or C or carrier
- •Hypotension (systolic blood pressure <90 mmHg)
- •Patients already taking ACE inhibitors or ARBs
- •Patients with STEMI requiring primary PCI
- •Patients pregnant or breast-feeding or child-bearing potential
- •Patients who are lack of intention for effective contraception
- •Patients with history of previous enrollment into a clinical trials within 3 months
- •Allergic or contraindicated to Angiotensin II antagonists
- •History of any arterial bypass or angioplastic intervention involving the target vessel
- •Luminal narrowing in the left main > 50% by visual inspection of angiogram
- •Visually-estimated angiographic reference segment diameter of <2.75mm or >4.0 mm
- •Presence of thrombus or complex plaque morphology in the target vessel that suggests a high likelihood of distal embolism
- •Severe tortuosity of the target vessel or any other anatomical reasons that the investigator deems
- •Inappropriate for IVUS procedures. Vessel with thrombus (on GS-IVUS), moderate or severe calcification, angulation
- •Culprit vessel in AMI
- •RWMA (Regional Wall Motion Abnormality) or scar tissue in the territory subtended by the studied lesion
研究组 & 干预措施
Fimasartan
Initial dose will be started with 60mg per day. At 4 week follow-up after the procedure, dose titration upto 120 mg per day will be made if the patient is not hypotensive.
干预措施: Fimasartan (Drug)
Placebo
Initial dose will be started with 60mg per day. At 4 week follow-up after the procedure, dose titration upto 120 mg per day will be made if the patient is not hypotensive.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in percent necrotic core (NC) volume of plaque by VH (Virtual Histology) in the "target segment" (within deferred vessel)
时间窗: baseline and 1 year
次要结局
- Change of total atheroma volume (TAV) and percent atheroma volume (PAV) of the target segment and the most diseased 10-mm segment (normalized to different segment length) with the largest plaque volume(baseline and 1 year)
- Change of OCT-defined fibrous cap thickness, the presence of plaque disruption, calcification or intraluminal thrombus within the target segment(baseline and 1 year)
- systolic and diastolic blood pressure(at 1 year follow-up)
- Percent change in minimal lumen area (MLA) in target segment(baseline and 1 year)
- Change of VH-IVUS (Intra Vascular UltraSound) detected plaque type from baseline(at 1 year)
- Change of percentage (%) of OCT (Optical Coherence Tomography)-defined TCFA (Thin Cap Fibrotic Atheroma) within the target segment from baseline(at 1 year)
- Change in high sensitive CRP (C-Reactive Protein)from baseline(at 1 year)
- Change of absolute area or percentages (%) of each plaque VH composition (fibrotic, fibrofatty, dense calcium, necrotic core) at minimal lumen area (MLA) and largest necrotic core area within the target segment(baseline and 1 year)
- Change of composition of OCT-defined fibrous, fibro-calcific, and lipid-rich plaque within the target segment(baseline and 1 year)
- Change of FFR in target segment from baseline(at 1 year)
研究者
Seung-Jung Park
MD,PhD, Chairman,Heart Institute, Asan Medical Center,University of Ulsan,College of Medicine
CardioVascular Research Foundation, Korea