Colchicine Versus Placebo in Acute Myocarditis Patients

• Status: Not yet recruiting
• Trial end date: 2027-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Myocarditis is an inflammatory disease of the heart, mostly caused by viruses. Patients with acute myocarditis are exposed to several complications: recurrence, ventricular arrhythmias (from 5 to 30%), heart failure (5-10%), death or heart transplantation (< 4%). To date, there is no specific treatment for myocarditis. Patient management only focuses upon empirical optimal care of arrhythmia and heart failure.

There is a strong rationale for using colchicine in acute myocarditis:

• the IL1 (Interleukin1) pathway plays a detrimental role in acute myocarditis. NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome assembly, and subsequent IL-1beta production, are profoundly inhibited by colchicine.

• colchicine has been shown to improve cardiac outcomes in inflammatory cardiac disorders, including pericarditis, coronary artery disease, and post pericardiotomy syndrome.

• In murine model of CVB3-induced myocarditis (coxsackievirus B3), colchicine improved myocarditis through reduction of NLRP3 activity.

• Small case series with improvement of left ejection fraction in myocarditis following low-dose colchicine in addition to conventional heart failure therapy have been reported.

With its pleiotropic anti-inflammatory effect in the pro-inflammatory cascade, reducing the myocardial damage and cell death induced during myocarditis, colchicine has the potential to reduce the risk of heart failure and ventricular arrhythmias. Finally, colchicine is a drug widely available, at low cost, and has a long and well-known safety record.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Fonds de Dotation ACTION; Hospices Civils de Lyon
• Treatments: Colchicine

Criteria

Inclusion Criteria:

• Symptom onset of 21 days or less,

• Chest pain and/or Heart failure symptoms and/or palpitations

• Troponins superior to 99 percentile of reference value,

• Myocarditis diagnostic confirmation (by Contrast-Enhanced Cardiac Magnetic Resonance (CMR), according to the Lake Louise criteria with the presence of myocardial damage),

• 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) or all recent acute illness

• 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, pace maker, defibrillator, history of hypersensitivity to gadoteric acid or to gadolinium contrast agents or to meglumine),

• Chronic treatment with corticosteroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 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

• 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

• 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,

• Participant under legal protection: under guardianship (trusteeship or curatorship)