Effect of colchicine on progression of known coronary atherosclerosis in patients with STable CoROnary artery disease CoMpared to placebo (EKSTROM) trial-rationale and design

Am Heart J. 2024 Nov:277:20-26. doi: 10.1016/j.ahj.2024.07.005. Epub 2024 Jul 17.

Abstract

Background: Cardiovascular disease is the major cause of mortality in the United States. Despite lifestyle modification and traditional risk factor control residual inflammatory risk remains an untreated concern. Colchicine is an oral, medication that has been used for gout, mediterranean fever and pericarditis for decades. In recent trials, colchicine has been shown to reduce major adverse cardiovascular events, however the mechanism of benefit remains unclear. The objective of the randomized, double-blind, placebo controlled EKSTROM trial is to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque.

Methods: Eighty-four participants will be enrolled after obtaining informed consent and followed for 12 months. Eligible patients will be randomly assigned to colchicine 0.5mg/day or placebo in a 1:1 fashion as add-on to their standard of care. All participants will undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months.

Results: As of November 2023, the study is 100% enrolled with an expected end of study by the second quarter of 2024. The primary endpoint is change in low attenuation plaque volume as measured by CCTA. Secondary endpoints include change in volume of different plaque types (including total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index), change in inflammatory markers (IL-6, IL-1β, IL-18, hs-CRP), change in pericoronary adipose tissue attenuation, change in epicardial adipose tissue volume and attenuation and change in brachial flow mediated dilation.

Conclusion: EKSTROM is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat. EKSTROM will provide important information on the mechanistic effects of colchicine on the cardiovascular system.

Trial registration: Registry: clinicaltrials.gov, Registration Number: NCT06342609 url: https://www.

Clinicaltrials: gov/study/NCT06342609?term=EKSTROM&rank=1.

Publication types

  • Clinical Trial Protocol
  • Randomized Controlled Trial

MeSH terms

  • Colchicine* / administration & dosage
  • Colchicine* / therapeutic use
  • Computed Tomography Angiography / methods
  • Coronary Angiography / methods
  • Coronary Artery Disease* / drug therapy
  • Disease Progression*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic* / drug therapy

Substances

  • Colchicine

Associated data

  • ClinicalTrials.gov/NCT06342609