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Coronary Artery DiseasePhase 3ESCALATENCT06469528

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

A Phase 3 study testing Colchicine 0.5 MG in people with Coronary Artery Disease, run by King's College Hospital NHS Trust.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Coronary Artery Disease
What is being tested?
Colchicine 0.5 MG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
No sites listed yet
Study dates
24 Jun 2024to 5 Oct 2026
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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)

Who cannot join

  • 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
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  • 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
  • History of hypersensitivity to the study drug or its constituents
  • 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
  • Any biologic drugs targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, tocilizumab)
  • Established long-term pharmacotherapy with a strong CYP3A4 inhibitor or a P-glycoprotein inhibitor (P-gpi) (e.g., macrolide antibiotics, ciclosporin, ketoconazole, itraconazole, voriconazole, HIV protease inhibitors, verapamil, diltiazem and disulfiram)
  • Contraindications to intravenous adenosine will exclude patients from adenosine induced hyperaemia
  • Any life-threatening condition with life expectancy <6 months that might prevent the patient from completing the study.

Trial locations and contacts

No sites are listed yet.

Anne-Marie Murtagh contact

+44 02032999000 ext. 31285

qm.khpcto@kcl.ac.uk

Michael McGarvey, MA MBBS MRCP contact

+44 02032999000 ext. 31285

michael.mcgarvey@nhs.net

About this study

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.

Read the detailed description
  1. Background and study aims Despite recent advances, coronary artery disease (CAD) remains the main cause of death worldwide. CAD occurs when the arteries bringing blood to the heart become narrowed by a build-up of fatty material within their walls. If this occurs gradually, it can cause chest discomfort i.e., angina. In a heart attack, the artery wall becomes inflamed and splits causing blood clot formation and an abrupt blockage of flow, resulting in severe pain and damaged heart muscle. Current treatments focus on reducing cholesterol, slowing the build-up of fatty material, and rapidly restoring blood flow during a heart attack. Chronic inflammation, acting in tandem with other risk factors, has been identified as playing a central role in CAD progression and its acute manifestations. Colchicine is a safe, well-tolerated, anti-inflammatory therapy used in the treatment of gout and other inflammatory conditions. Daily treatment with low-dose colchicine has proven effective in reducing rates of heart attack and death in large clinical trials, but use in routine practice remains low. A contributing factor to this reticence is uncertainty regarding the mechanism through which colchicine provides benefit. This study is designed to address this knowledge gap.
  2. Who can participate? Patients aged 18 to 90 years old with coronary artery disease and high clinical risk
  3. What does the study involve?

Using traditional markers of clinical risk and state-of-the-art imaging from inside the coronary artery, the researchers will identify patients with CAD and the greatest clinical risk. Eligible patients, already established on statin therapy will be allocated to a six-month course of low-dose colchicine plus usual care, or usual care only. Researchers, participants, and usual clinicians will be aware of the allocation during the study.

After 6 months, the researchers will assess the impact of colchicine on the appearance of individual coronary artery lesions, blood flow in the large and small blood vessels of the heart. This study will provide a detailed assessment of colchicine and its mechanism of action in CAD.

Being tested
Colchicine 0.5 MG
Keywords
Chronic coronary syndromes
Medical subject headings
Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Colchicine 0.5 MGDrug

    Low dose daily colchicine

Study groups in NCT06469528
Study groupRoleWhat they receive
Low dose colchicine 0.5mg ODExperimentalLow dose colchicine 0.5mg OD for 6 months
Receives: Drug: Colchicine 0.5 MG
Guideline directed therapyNo interventionGuideline directed therapy; participants will be maintained on maximal tolerated dose of established statin therapy (>4 weeks)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6months

Secondary outcomes (14)

  1. Major adverse clinical events

    Major adverse cardiovascular event (MACE): Composite of cardiovascular death, non-fatal MI, unplanned revascularisation and ischaemic stroke

    Measured: 6 months

  2. Acute kidney injury

    AKI secondary to contrast induced nephropathy

    Measured: 6 months

  3. Major bleeding events (BARC 3-5)

    Periprocedural major bleeding events (BARC 3-5)

    Measured: 6 months

  4. Hospitalisation with serious infection

    Hospitalisation requiring intravenous antibiotics

    Measured: 6 months

  5. % change in minimal fibrous cap thickness

    Percentage change in minimal fibrous cap thickness, as determined by OCT, in a defined arterial region of interest

    Measured: 6 months

  6. % change in maximal lipid arc

    Percentage change in lipid arc, as determined by OCT, in a defined arterial region of interest

    Measured: 6 months

  7. Percentage change in lipid index

    Percentage change in lipid index, as determined by OCT, in a defined arterial region of interest

    Measured: 6 months

  8. Absolute change in maximum lipid core burden index in a 4-mm segment (maxLCBI4mm)

    Absolute change in maximum lipid core burden index in a 4-mm segment (maxLCBI4mm), as determined by NIRS, in a defined arterial region of interest

    Measured: 6 months

  9. Relative change (%) in maximum lipid core burden index in a 4-mm segment (maxLCBI4mm)

    Relative change (%) in maximum lipid core burden index in a 4-mm segment (maxLCBI4mm), as determined by NIRS, in a defined arterial region of interest

    Measured: 6 months

  10. Change in total atheroma volume

    Change in percent atheroma volume, as determined by IVUS, in a defined arterial region of interest

    Measured: 6 months

  11. Absolute and percentage change in coronary flow reserve (CFR)

    Absolute and percentage change in coronary flow reserve (CFR), measured in artery of interest

    Measured: 6 months

  12. Absolute and percentage change in index of microvascular resistance (IMR)

    Absolute and percentage change in index of microvascular resistance (IMR), measured in artery of interest

    Measured: 6 months

  13. Absolute and percentage change in vessel fractional flow reserve (FFR)

    Absolute and percentage change in vessel fractional flow reserve (FFR), measured in artery of interest

    Measured: 6 months

  14. Percentage change in high-sensitivity c-reactive protein (hs-CRP)

    Percentage change in high-sensitivity c-reactive protein (hs-CRP)

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2024
  2. Study start24 Jun 2024 (estimated)
  3. Primary completion5 Oct 2025 (estimated)
  4. Study completion5 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Single centre, open-label prospective, randomised controlled trial; patients randomised 1:1 to low-dose colchicine 0.5mg OD vs guideline directed medical therapy
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06469528
Sponsor's protocol ID
KCH23-187
Acronym
ESCALATE
Status last verified
Jun 2024
First submitted
10 Jun 2024
Last updated
21 Jun 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Colchicine 0.5 MG in people with Coronary Artery Disease, run by King's College Hospital NHS Trust.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Anne-Marie Murtagh (+44 02032999000 ext. 31285, qm.khpcto@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute change in minimal fibrous cap thickness (time frame: 6months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06469528.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2024.

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