Rationale and design of the REMBRANDT trial: A phase 3 study to evaluate the effect of obicetrapib/ezetimibe on coronary plaque characteristics.

IF 3.5 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
American heart journal Pub Date : 2025-12-01 Epub Date: 2025-07-17 DOI:10.1016/j.ahj.2025.07.012
Cian P McCarthy, Christie M Ballantyne, Ron Blankstein, Matthew J Budoff, Marc Ditmarsch, C Michael Gibson, John J P Kastelein, Ann Marie Navar, Stephen J Nicholls, Kausik K Ray, Cheerag Shirodaria, Michelle C Williams, James L Januzzi
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引用次数: 0

Abstract

Background: Obicetrapib is a potent, selective cholesteryl ester transfer protein (CETP) inhibitor that significantly lowers low-density lipoprotein cholesterol (LDL-C). Additive reductions in LDL-C occur when obicetrapib is combined with ezetimibe. The impact of obicetrapib and ezetimibe fixed-dose combination (FDC) on coronary plaque burden is unknown. Favorable changes in noncalcified coronary atherosclerotic plaque volume (NCPV) may indicate a potential beneficial effect on atherosclerotic cardiovascular disease (ASCVD) events.

Methods: REMBRANDT is a placebo-controlled, double-blind, randomized trial designed to assess the efficacy of obicetrapib and ezetimibe FDC on coronary plaque burden. Individuals aged 45 years or older with ASCVD (imaging evidence of vascular disease or clinically manifested ASCVD) and an LDL-C of ≥70 mg/dL despite maximally tolerated lipid-modifying therapy are eligible to participate. Eligible participants (N = 300) will be randomized in a 1:1 ratio to obicetrapib 10 mg and ezetimibe 10 mg FDC once daily or placebo tablet once daily. The primary efficacy outcome of REMBRANDT is percent change in total NCPV from baseline to 18 months as assessed by coronary computed tomographic angiography (CCTA). Secondary endpoints include absolute change in total NCPV, percent and absolute change in NCPV in the most diseased coronary segment, percent change in LDL-C, and change in perivascular fat attenuation index from baseline to 18 months.

Conclusion: The REMBRANDT trial will determine whether the favorable effects of obicetrapib and ezetimibe FDC on LDL-C translate to a reduction in coronary plaque burden as a potential mechanism for ASCVD risk reduction.

Clinical trial registration: NCT06305559.

REMBRANDT试验的基本原理和设计:一项评估obicetrapib/ezetimibe对冠状动脉斑块特征影响的3期研究。
Obicetrapib是一种有效的选择性胆固醇酯转移蛋白(CETP)抑制剂,可显著降低低密度脂蛋白胆固醇(LDL-C)。当obictrapib与ezetimibe联合使用时,LDL-C会发生累加性降低。obicetrapib和ezetimibe固定剂量组合(FDC)对冠状动脉斑块负荷的影响尚不清楚。非钙化冠状动脉粥样硬化斑块体积(NCPV)的有利变化可能表明对动脉粥样硬化性心血管疾病(ASCVD)事件的潜在有益影响。方法:REMBRANDT是一项安慰剂对照、双盲、随机试验,旨在评估obicetrapib和ezetimibe FDC对冠状动脉斑块负荷的疗效。年龄在45岁或以上的动脉粥样硬化性心血管疾病(血管疾病的影像学证据或临床表现的ASCVD)患者,尽管接受了最大耐受的脂质调节治疗,但LDL-C≥70 mg/dL的患者有资格参加。符合条件的参与者(N=300)将按1:1的比例随机分配至obictrapib 10mg和ezetimibe 10mg FDC,每日一次或安慰剂片,每日一次。REMBRANDT的主要疗效指标是通过冠状动脉计算机断层血管造影(CCTA)评估的从基线到18个月的总NCPV变化百分比。次要终点包括总NCPV的绝对变化,最病变冠状动脉段NCPV的百分比和绝对变化,LDL-C的百分比变化,以及从基线到18个月血管周围脂肪衰减指数的变化。结论:REMBRANDT试验将确定obictrapib和ezetimibe FDC对LDL-C的有利作用是否转化为降低冠状动脉斑块负担,作为降低ASCVD风险的潜在机制。临床试验注册:NCT06305559。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
American heart journal
American heart journal 医学-心血管系统
CiteScore
8.20
自引率
2.10%
发文量
214
审稿时长
38 days
期刊介绍: The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.
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