Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients With Stable Coronary Artery Disease (EKSTROM)

Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients With STable CoROnary Artery Disease CoMpared to Placebo - EKSTROM Trial

This is a randomized double-blind, placebo-controlled, investigator-initiated trial that compares Colchicine 0.5mg/day with placebo, among patients with stable CAD. Subjects will be educated to maintain medication compliance with other prescribed medications.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Colchicine 0.5 MG

Detailed Description

The goal of this study is to evaluate whether treatment with Colchicine results in greater change of low attenuation plaque volume from baseline level when compared to placebo in subjects with stable Coronary Artery Disease (CAD). The Primary objective of the study is to determine progression rates of low attenuation plaque under influence of Colchicine as compared to placebo. The study will also look to determine effects of Colchicine on the morphology and composition non -calcified coronary plaque, progression of total plaque volume, progression of high vulnerability features of plaque and to assess whether these effects are modulated by a change in HsCRP and other markers of inflammation (HsCRP, IL-6, IL-1α, IL-1β, IL-18) as well as the effect on Pericoronary adipose tissue (PCAT) and Epicardial adipose tissue (EAT) volume and well as on the endothelial function.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 30-85 years
2. Proven coronary artery disease; as evidenced by coronary angiography, CT coronary angiography or a Coronary Artery Calcium Score (Agatston score >400).
3. Clinically stable for at least six months
4. Patients should have no major competing co-morbidities or contra-indication to colchicine therapy
5. Patients must be considered to be compliant with their usual therapy
6. Willingness to be on birth control for women of childbearing age or established postmenopausal for at least 1 year
7. Patients must provide written informed consent after the scope and nature of the investigation has been explained to them.
8. Patients must be considered to be compliant with their usual therapy
9. Patients must provide written informed consent after the scope and nature of the investigation has been explained to them.
10. Patients must be able and willing to comply with the requirements of this study protocol

Exclusion Criteria:

1. Women who are pregnant, breast feeding or may be considering pregnancy during the study period
2. Renal impairment as evidenced by a serum creatinine >150 μmol/l or estimated glomerular filtration rate (eGFR) <50mL/min/1.73m2
3. Severe heart failure - systolic or diastolic New York Heart Association Functional classification 3 or 4
4. Moderate or severe valvular heart disease considered likely to require intervention
5. Dependency, frailty or a predicted life expectancy < 5 years
6. Peripheral neuritis, myositis or marked myo-sensitivity to statins
7. Requirement for long term colchicine therapy for any other reason
8. Current enrollment in another trial
9. Patients with inflammatory bowel disease (Crohn's disease or ulcerative colitis) or patients with chronic diarrhea
10. Any unstable medical, psychiatric or substance abuse disorder that in the opinion of the investigator or principal investigator is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study
11. Patient with progressive neuromuscular disease of Creatine Phosphokinase (CPK) level >3 times the upper limit of normal as measured within the past 30 days and determined to be non-transient through repeat testing.
12. Patients already taking long term colchicine therapy for any other reason
13. History of malignancy within the last 5 years (other than skin cancer) or evidence of active cancer which would require concomitant cancer chemotherapy
14. Hematological or biochemical values at screening outside the reference ranges considered as clinically significant in the opinion of the investigator or PI.
15. Allergy to contrast material

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Colchicine; 0.5 milligram (mg) per day of Colchicine orally administered over the period of 52 weeks	Drug: Colchicine 0.5 MG; 0.5mg per day of Colchicine orally administered; Other Names: Colcrys; Mitigare
Placebo Comparator: Placebo; 0.5mg per day of Placebo orally administered over the period of 52 weeks	Drug: Colchicine 0.5 MG; 0.5mg per day of Colchicine orally administered; Other Names: Colcrys; Mitigare

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of change in low attenuation plaque volume as measured by multidetector computed tomography (MDCT) angiography	Reduction of low attenuation plaque volume from baseline (start of the study) till the final visit will be measured using Coronary Computed Tomography Angiography (CTA).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Colchicine on markers of inflammation using laboratory tests	To determine the effect of Colchicine on markers of inflammation (IL-6, IL-1α, IL-1β, IL-18 high sensitivity C-reactive protein)	12 months
Effects of Colchicine on Pericoronary Adipose Tissue (PCAT) volume using CTA	To determine the effects of Colchicine on PCAT volume.	12 months
Effects of Colchicine on Epicardial Adipose Tissue (EAT) volume using CTA	To determine the effects of Colchicine on EAT volume.	12 months
Effect of Colchicine on the markers of Endothelial Function using Flow-mediated dilation (FMD)	To determine the effect of Colchicine on Endothelial function using FMD.	12 months

Collaborators and Investigators

• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Investigators: Principal Investigator: Matthew Budoff, MD, The Lundquist Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Actual): September 7, 2024
• Study Completion (Actual): September 7, 2024

Study Registration Dates

• First Submitted: March 16, 2024
• First Submitted That Met QC Criteria: March 28, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 10, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 32857-01-EKSTROM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes