Colchicine Versus Placebo in Acute Myocarditis Patients

This study is a prospective, randomized, multicenter, double blind, controlled versus placebo, phase III study in which two groups of participants are compared: a group treated with the experimental treatment Colchicine (in addition to standard of care therapy) compared to a control group that receive the corresponding placebo (in addition to standard of care therapy).

The inclusion visit takes place during the initial hospitalization stay. The study is presented to all patients presenting with acute myocarditis symptoms and inclusion criteria, hospitalized in participating centers.

Once eligible participants have been informed and signed their informed consent, they are randomized (1:1) by a centralized web system (IWRS) in the experimental group (Colchicine) or the control group (Placebo).

Participants receive then a numbered box with three months' treatment of Colchicine or placebo. The treatment must start at least within 72h after randomization. Another dispensing is performed during the three months' follow-up visit.

All randomized participants are followed during six months after the end of the treatment.

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)