ESCALATion of Medical Therapy Following Multimodality Plaque Evaluation in High-risk Chronic Coronary Syndromes

NCT06469528 | Not Yet Recruiting Phase 3

• 1 other identifier: KCH23-187
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

ESCALATE will provide a thorough investigation of how anti-inflammatory therapy, with low-dose colchicine, affects patients with stable coronary artery disease. Using traditional clinical risk factors and multimodality intracoronary imaging, the investigators will identify patients with the greatest clinical risk. Participants will undergo repeat multimodality intracoronary imaging assessment at 6 months to measure the impact once-daily low-dose colchicine therapy on the structure and function of coronary arteries. This study will provide valuable insights into how anti-inflammatory therapies, such as colchicine, may improve outcomes in patients with coronary artery disease.

Conditions

Coronary Artery Disease

Keywords

Chronic coronary syndromes

Outcome Measures

Primary Outcomes (1)

• Absolute change in minimal fibrous cap thickness

  The absolute change (µm) in minimal fibrous cap thickness, in a defined arterial region of interest, as assessed by OCT

  6months

Secondary Outcomes (14)

• Major adverse clinical events

  6 months

• Acute kidney injury

  6 months

• Major bleeding events (BARC 3-5)

  6 months

• Hospitalisation with serious infection

  6 months

• % change in minimal fibrous cap thickness

  6 months

Study Arms (2)

Low dose colchicine 0.5mg OD

EXPERIMENTAL

Low dose colchicine 0.5mg OD for 6 months

Drug: Colchicine 0.5 MG

Guideline directed therapy

NO INTERVENTION

Guideline directed therapy; participants will be maintained on maximal tolerated dose of established statin therapy (\>4 weeks)

Interventions

Colchicine 0.5 MG DRUG

Low dose daily colchicine

Low dose colchicine 0.5mg OD

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide written informed consent
• Age 18 to 90 years old
• Male, or female of non-child-bearing potential
• Elevated clinical risk, as evidenced by ≥1 of:
• Previous spontaneous acute myocardial infarction (diagnosed according to the universal MI criteria) with or without persistent ST-segment elevation
• Previous stroke or intervention for peripheral arterial disease (i.e., evidence of atherosclerotic disease affecting \>1 vascular bed)
• Established diagnosis of diabetes mellitus
• 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%
• Documented evidence of coronary artery disease, with an angiographically moderate stenosis on invasive coronary angiography (30-80%)
• \- At least one non-flow limiting (FFR \>0.80) moderate lesion with TCFA (minimum fibrous cap thickness of less than or equal to120µm and lipid arc \>90°)
• History of prescribed statin therapy, at a stable dose, for \>4 weeks
• Evidence of residual inflammation at baseline (i.e., high-sensitivity CRP ≥2)

You may not qualify if:

• Women who are pregnant, breast feeding, or of child-bearing potential
• 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
• Previous spontaneous acute myocardial infarction (diagnosed according to the universal MI criteria) with or without persistent ST-segment elevation \<4 weeks from recruitment
• Previous coronary artery bypass grafting
• Known chronic total occlusion of coronary artery
• Chronic kidney disease with eGFR \<50 mL/min/1.73 m2 per MDRD formula or renal replacement therapy at baseline assessment
• 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
• Symptoms of severe heart failure (systolic or diastolic) with New York Heart Association (NYHA) Functional Classification 3 or 4
• Moderate or severe valvular heart disease considered likely to require intervention
• History of blood dyscrasia including anaemia, thrombocytopenia, neutrophilia, leukopenia or other abnormality of blood count at baseline
• Peripheral neuritis, myositis or marked myo-sensitivity to statins
• A history of alcohol and/or substance abuse that could interfere with the conduct of the trial
• Patients with suspected or proven immunocompromised state, including:
• those with evidence of Human Immunodeficiency Virus (HIV) infection; Patients on anti-retroviral therapy are excluded
• those with any other medical condition which in the opinion of the investigator places the patient at unacceptable risk for participation in immunomodulatory therapy

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead
• King's College London: collaborator

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Nilesh Pareek, MA MBBS PhD

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne-Marie Murtagh

CONTACT

+44 02032999000; qm.khpcto@kcl.ac.uk

Michael McGarvey, MA MBBS MRCP

CONTACT

+44 02032999000; michael.mcgarvey@nhs.net

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single centre, open-label prospective, randomised controlled trial; patients randomised 1:1 to low-dose colchicine 0.5mg OD vs guideline directed medical therapy

Study Record Dates

• First Submitted: June 10, 2024
• First Posted: June 21, 2024
• Study Start: June 24, 2024
• Primary Completion: October 5, 2025
• Study Completion (Estimated): October 5, 2026
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share