Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
juillet 2024
juillet 2028
18 septembre 2025
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.
Etablissements
Critères
Tous
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 (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.
- 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 (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.
- 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, non-MR compatible
cardiac devices (pace maker or 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, azole antifungals,
vitamin K antagonists]
- Participant under legal protection: under guardianship (trusteeship or curatorship)