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

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Status and phase: Completed; Phase 4

Conditions: Coronary Artery Disease

Treatments: Drug: Colchicine 0.5 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT06342609

32857-01-EKSTROM

Details and patient eligibility

About

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.

Full 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.

Enrollment: 84 patients

Sex: All

Ages: 30 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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84 participants in 2 patient groups, including a placebo group

Colchicine

Active Comparator group

Description:

0.5 milligram (mg) per day of Colchicine orally administered over the period of 52 weeks

Treatment:

Drug: Colchicine 0.5 MG

Placebo

Placebo Comparator group

Description:

0.5mg per day of Placebo orally administered over the period of 52 weeks

Treatment:

Drug: Colchicine 0.5 MG