What is the Ekstrom trial procedure and how is it performed?

The Ekstrom Trial Procedure: Method and Implementation

The Ekstrom trial is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque progression in patients with stable coronary artery disease. 1

Trial Design and Methodology

• The trial enrolls patients with stable coronary artery disease who are randomized in a 1:1 fashion to receive either colchicine 0.5mg/day or placebo as add-on to standard care 1
• All participants undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months to assess changes in plaque characteristics 1
• The study follows Good Clinical Practice principles with emphasis on proper informed consent and the right to withdraw from the trial 2
• An appropriate ethical committee approves the study procedure to ensure patient safety and scientific validity 2

Primary and Secondary Endpoints

• The primary endpoint is change in low attenuation plaque volume as measured by CCTA 1
• Secondary endpoints include:
  • Changes in different plaque types (total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index) 1
  • Changes in inflammatory markers (IL-6, IL-1β, IL-18, hs-CRP) 1
  • Changes in pericoronary adipose tissue attenuation 1
  • Changes in epicardial adipose tissue volume and attenuation 1
  • Changes in brachial flow-mediated dilation 1

Patient Monitoring and Assessment

• Patients undergo rigorous neurological evaluations at defined time points after treatment initiation (typically at 24 hours, 72 hours, 7-10 days, 30 days, and 90 days) 2
• Additional evaluations are performed when any signs of neurological deterioration occur 2
• Patients are carefully monitored throughout the study period for adverse events, which are defined as any untoward medical occurrence irrespective of causal relation with the procedure or treatment 2

Informed Consent Considerations

• Before enrollment, patients must receive comprehensive information about:
  • The novel nature of the intervention being studied 3
  • Potentially unknown risks and benefits 3
  • The experience level of the providers involved in the procedure 3
  • Available outcome data when applicable 3

Data Collection and Analysis

• The trial employs a randomized, double-blind crossover protocol where patients are randomized to treatment or placebo conditions 2
• Both patients and researchers remain unaware of these allocations to minimize bias 2
• Treatment evaluation includes assessment of various factors including symptom severity, quality of life, and functional outcomes 2

Importance and Limitations

• The Ekstrom trial is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat 1
• Results from this single trial should be interpreted with caution, as single-trial evidence is generally less reliable than its statistical analysis suggests 4
• The confidence intervals from single trials may be narrower than they should be when heterogeneity is not accounted for, with the ratio of confidence interval widths being 1.15,1.41, and 2.00 when heterogeneity I² values are 0.25,0.50, and 0.75, respectively 4

Current Status

• As of November 2023, the study is 100% enrolled with expected completion by the second quarter of 2024 1
• The trial is registered on clinicaltrials.gov with Registration Number: NCT06342609 1

The Ekstrom trial represents an important contribution to understanding the mechanistic effects of colchicine on the cardiovascular system, though its findings should be considered alongside other evidence when making clinical decisions about treatment approaches for coronary artery disease.