Obicetrapib
REMBRANDT trial design: 300 ASCVD patients to test whether obicetrapib plus ezetimibe shrinks coronary plaque on CT angiography (Am Heart J 2025)
Original title: Rationale and design of the REMBRANDT trial: A phase 3 study to evaluate the effect of obicetrapib/ezetimibe on coronary plaque characteristics
The rationale and design paper for REMBRANDT, a placebo-controlled, double-blind, randomised phase 3 trial testing an obicetrapib 10 mg plus ezetimibe 10 mg fixed-dose combination once daily against placebo in 300 participants aged 45 or older with atherosclerotic cardiovascular disease and LDL-C of 70 mg/dL or above despite maximally tolerated therapy. The primary outcome is percent change in total non-calcified coronary plaque volume from baseline to 18 months by coronary CT angiography, with secondary endpoints covering absolute plaque change, the most diseased segment, LDL-C change and perivascular fat attenuation. The trial will test whether the LDL-C lowering from obicetrapib and ezetimibe translates into a measurable reduction in coronary plaque burden, a mechanistic bridge toward cardiovascular outcomes. Registered as NCT06305559; no results reported here.
Original 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.
ezetimibeobicetrapibphase 3plaque imaging
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.