Colchicine treatment for patients with acute myocarditis

Colchicine Versus Placebo in Acute Myocarditis Patients to Reduce Late Gadolinium Enhancement Mass on Cardiac Magnetic Resonance and the Risk of Clinical Outcomes: The ARGO Trial

This study is testing if colchicine can help hospitalized patients with acute myocarditis feel better and improve their heart health compared to a placebo.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 2 sites (Bron and 1 other locations)
• Trial ID: NCT05855746 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial investigates the efficacy of colchicine compared to a placebo in patients diagnosed with acute myocarditis. The study involves a randomized, double-blind, multicenter approach where participants receive either colchicine or a placebo alongside standard care. Eligible patients will be hospitalized with symptoms of myocarditis and will be monitored for six months following treatment. The trial aims to assess whether colchicine can improve cardiac outcomes by targeting inflammation associated with the condition.

Who should consider this trial

Good fit: Ideal candidates are individuals with acute myocarditis symptoms that began within the last 21 days and who meet specific diagnostic criteria.

Not a fit: Patients with ischemic heart disease or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a specific therapeutic option for patients suffering from acute myocarditis, potentially reducing complications and improving recovery.

How similar studies have performed: Previous studies have shown colchicine to be effective in other inflammatory cardiac conditions, suggesting potential success in this novel application.

Eligibility criteria

Inclusion Criteria:

* Symptom onset of 28 days or less,
* Myocarditis initially presenting with chest pain and/or Heart failure symptoms and/or palpitations
* Troponins superior to 99 percentile of reference value, at any time between admission and inclusion
* Myocarditis diagnostic confirmation (by Contrast-Enhanced Cardiac Magnetic Resonance (CMR), according to the Lake Louise criteria (2009 or later),
* No evidence for ischemic heart disease on coronary angiography or coronary computed tomography angiography for patients with age superior to 40-year-old with one or more cardiovascular risk factor (hypertension, smoking, hypercholesterolemia, diabetes, personal or family history of coronary artery disease),
* Woman of child-bearing age with an effective contraception method according to the investigator for the duration of treatment and one month after,
* Man accepting effective contraception for the duration of treatment and one month after,
* Participant with affiliation to the French Health Care System "sécurité sociale",
* Written informed consent of the patient obtained.

Exclusion Criteria:

* Cardiogenic shock requiring inotropes or vasopressors (patients with inotropes discontinued for more than 24 hours can be enrolled)
* Giant cell myocarditis or eosinophilic myocarditis
* Acute coronary syndrome or known coronary stenosis superior to 50%
* Toxic cardiomyopathy
* Active chronic inflammatory disease, chronic active infection, evolving cancer
* A recent severe sepsis (7 days)
* Hypersensitivity to Investgational Medical Product's active substances (colchicine) or to any of the excipients (including lactose, sucrose, microcrystalline cellulose, colloidal silica, magnesium stearate, colourants : E127, Dual Red 40 )
* Any known contra-indication to CMR or associated contract products (claustrophobia; intra-ocular metal foreign bodies, clips such as cerebral, carotid, or aortic aneurysm, cochlear implants, any implant held in by magnet, history of hypersensitivity to gadoteric acid or to gadolinium contrast agents or to meglumine). Patients with an implantable cardioverter-defibrillator (ICD) or pacemaker (PM) are also excluded due to the risk of imaging artifacts, which may compromise the reliable quantification of late gadolinium enhancement (LGE).
* Chronic treatment with corticosteroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or high-dose aspirin or immunosuppressant.
* Sarcoidosis
* Severe liver (Child Pugh C) or known renal dysfunction (known Glomerular Filtration Rate (GFR) less or equal to 30 ml/min according Cockroft),
* Cytopenia : hemoglobin less than 100 grams/L, white blood cell count less than 3.0 G/L, platelet count less than 100 G/L between admission and inclusion (within 7 days)
* Major digestive disorders (chronic diarrhea, inflammatory disease of the digestive tract as uncontrolled ulcerative colitis or active Crohn disease)
* Immunosuppression, spinal cord aplasia
* Hemopathy
* Hypereosinophilia more than 0.5 G/L between admission and inclusion
* Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive local laboratory test,
* Administration of any investigational drug or participation in another interventional trial, within 30 days before randomization,
* Participant under treatment having an interaction with colchicine \[macrolides (telithromycin, azithromycin, clarithromycin, dirithromycin, erythromycin, josamycin, midecamycin, roxithromycin), pristinamycin,, cyclosporine, verapamil, all protease inhibitors, telaprevir, CYP3A4 powerful inhibitors, azole antifungals, vitamin K antagonists\]
* Participant under legal protection: under guardianship (trusteeship or curatorship)

Where this trial is running

Bron and 1 other locations

• Unité de Soins Intensifs Cardiologiques - Hôpital Cardiovasculaire Louis Pradel — Bron, France (Recruiting)
• Institut de Cardiologie - APHP Pitié Salpêtrière — Paris, France (Recruiting)

Study contacts

• Study coordinator: Thomas BOCHATON

Conditions Acute Myocarditis; Myocarditis; Inflammation; Colchicine