Targeted use of low-dose colchicine in patients with coronary artery disease and high clinical risk

Phase 4

Conditions: Chronic inflammation
atherosclerosis
coronary artery disease
chronic coronary syndromes
Circulatory System

Registration Number: ISRCTN46375134

Lead Sponsor: King's College Hospital NHS Foundation Trust

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 50

Inclusion Criteria

1. Ability to provide written informed consent
2. Age 18 to 90 years old
3. Male, or female of non-child-bearing potential
4. Elevated clinical risk, as evidenced by =1 of:
4.1. Previous spontaneous acute myocardial infarction (diagnosed according to the universal MI criteria) with or without persistent ST-segment elevation
4.2. Previous stroke or intervention for peripheral arterial disease (i.e., evidence of atherosclerotic disease affecting >1 vascular bed)
4.3. Established diagnosis of diabetes mellitus
4.4. Systemic Coronary Risk Estimation 2 (SCORE2) or Systemic Coronary Risk Estimation 2 – Older Persons (SCORE2-OP) algorithm 10-year risk of fatal and non-fatal myocardial infarction or stroke >10%
5. Documented evidence of coronary artery disease, with an angiographically moderate stenosis on invasive coronary angiography (30-80%)
6. At least one non-flow limiting (FFR >0.80) moderate lesion with TCFA (minimum fibrous cap thickness of <120µm and lipid arc >90°)
7. History of prescribed statin therapy, at a stable dose, for >4 weeks
8. Evidence of residual inflammation at baseline (i.e., high-sensitivity CRP =2)

Exclusion Criteria

1. Women who are pregnant, breastfeeding, or of child-bearing potential
2. Symptoms of unstable angina, characterised as: angina at rest; new onset of severe exertional angina (CCS grade III or higher for <4 weeks); or distinct, sudden, intensification of previously stable angina
3. Previous spontaneous acute myocardial infarction (diagnosed according to the universal MI criteria) with or without persistent ST-segment elevation <4 weeks from recruitment
4. Previous coronary artery bypass grafting
5. Known chronic total occlusion of coronary artery
6. Chronic kidney disease with eGFR <50 mL/min/1.73 m2 per MDRD formula or renal replacement therapy at baseline assessment
7. Known active or recurrent hepatic disorder (including cirrhosis, hepatitis B and hepatitis C, or confirmed ALT/AST levels > 3 times ULN or total bilirubin > 2 times ULN) at baseline assessment
8. Symptoms of severe heart failure (systolic or diastolic) with New York Heart Association (NYHA) Functional Classification 3 or 4
9. Moderate or severe valvular heart disease considered likely to require intervention
10. History of blood dyscrasia including anaemia, thrombocytopenia, neutrophilia, leukopenia or other abnormality of blood count at baseline
11. Peripheral neuritis, myositis or marked myo-sensitivity to statins
12. A history of alcohol and/or substance abuse that could interfere with the conduct of the trial
13. Patients with suspected or proven immunocompromised state, including:
13.1. Those with evidence of Human Immunodeficiency Virus (HIV) infection; Patients on anti-retroviral therapy are excluded
13.2. Those with any other medical condition which in the opinion of the investigator places the patient at unacceptable risk for participation in immunomodulatory therapy
14. History of hypersensitivity to the study drug or its constituents
15. Patients who have received an investigational drug or device within 30 days (inclusive) of baseline assessment, or who are expected to participate in any other investigational drug or device study during the conduct of this trial
16. Any biologic drugs targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, tocilizumab)
17. Established long-term pharmacotherapy with a strong CYP3A4 inhibitor or a P-glycoprotein inhibitor (P-gp) (e.g., macrolide antibiotics, ciclosporin, ketoconazole, itraconazole, voriconazole, HIV protease inhibitors, verapamil, diltiazem and disulfiram)
18. Contraindications to intravenous adenosine will exclude patients from adenosine induced hyperaemia
19. Any life-threatening condition with life expectancy <6 months that might prevent the patient from completing the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Minimal fibrous cap thickness in a defined arterial region of interest, as assessed by intracoronary optical coherence tomography (OCT) at baseline and 6 months

Secondary Outcome Measures