Rationale and Design of the Rembrandt Trial: A Phase 3 Study To Evaluate the Effect of Obicetrapib/Ezetimibe on Coronary Plaque Characteristics

Authors

• 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

Language

English

Publication Date

12-1-2025

Journal

American Heart Journal

DOI

10.1016/j.ahj.2025.07.012

PMID

40683616

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.

Keywords

Aged, Female, Humans, Male, Middle Aged, Anticholesteremic Agents, Cholesterol Ester Transfer Proteins, Cholesterol, LDL, Coronary Angiography, Coronary Artery Disease, Double-Blind Method, Drug Combinations, Drug Therapy, Combination, Ezetimibe, Plaque, Atherosclerotic, Clinical Trials, Phase III as Topic, Randomized Controlled Trials as Topic

Comments

Clinical trial registration: NCT06305559.

Published Open-Access

yes

Recommended Citation

McCarthy, Cian P; Ballantyne, Christie M; Blankstein, Ron; et al., "Rationale and Design of the Rembrandt Trial: A Phase 3 Study To Evaluate the Effect of Obicetrapib/Ezetimibe on Coronary Plaque Characteristics" (2025). Faculty, Staff and Students Publications. 6685.
https://digitalcommons.library.tmc.edu/baylor_docs/6685