Refer to the "Detailed Description" section.
Introduction: Acute myocarditis (AM) is an inflammatory disease of the heart. The incidence is approximately 22 out of 100 000 patients annually. Clinically, it ranges from subclinical pauci-symptomatic forms to life-threatening arrhythmias, cardiogenic shock and sudden cardiac death. In approximately more than 70% of cases, AM resolves spontaneously. In the remaining patients, it evolves to a poor prognosis with left ventricular dilatation, reduced cardiac contractility and progression to chronic heart failure. Complicated AM is defined as an AM with Left Ventricular Ejection Fraction (LVEF) \< 50% and/or a sustained ventricular arrhythmia and/or a hemodynamic instability. Complicated AM is often associated with a poor prognosis (in example risk of heart transplantation of 10.4% at 30 days and 14.7% at 5-year follow up) whereas uncomplicated AM have none. Administration of immunosuppressive treatment (IT) is still debated. According to experts' consensus, immunosuppressive treatment should be considered in complicated AM and should be used in recommended in case of fulminant myocarditis (acute myocarditis with a presentation of cardiogenic shock, ventricular arrhythmias, or multiorgan system failure). Nevertheless, there is no data on use of glucocorticoids (GC) in complicated AM. Early application of high dose of GC in AM can control the cytokine storm and the inflammatory response, rather than suppressing the overall immune response. Best timing for their administration remains unknown. The aim of this multicenter controlled randomized study is to demonstrate the benefit of high dose of GC therapy on mortality and cardiac events in patients with AM and left ventricular (LV) dysfunction. Hypothesis/Objective: The main objective is to evaluate in patients with acute myocarditis with left-ventricular dysfunction the efficacy of a pulse of Methylprednisolone IV for 3 days at diagnosis followed by Prednisone per os versus placebo IV followed by placebo per os in association with conventional Heart Failure (HF) therapy on the occurrence of Major Cardiovascular Events (MACE) and/or persistence of left ventricular dysfunction defined as LVEF \< 50% and/or Global Longitudinal Strain (GLS) \< -16% between baseline and at 6 months. The primary endpoint is the Major Cardiovascular Events (MACE) and/or persistence of left ventricular dysfunction defined as LVEF \< 50% and/or Global Longitudinal Strain (GLS) \< - 16% between baseline (D-2) and 6 months (M6) follow up. MACE is a combined criterion that includes all-cause mortality, heart failure hospitalization, sustained ventricular arrhythmia, heart transplantation or assistance and recurrent acute myocarditis with LV dysfunction at 6 months. Method: Phase III, prospective, randomized, placebo controlled, superiority, double blinded trial with 2 parallel groups randomized in a 1:1 ratio: * Experimental group: Methylprednisolone IV for 3 days followed by Prednisone per os + conventional HF treatment. * Control group: placebo of Methylprednisolone IV followed by placebo of Prednisone per os + conventional HF treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
420
Patients will take intravenous administration of Methylprednisolone (500mg/100ml by IV over 30 minutes per day) for 3 days.
After intravenous administration of Methylprednisolone patients will take by oral Prednisone 1mg/kg per day once a day (with a maximum dose of 90 mg per day for patients weighing \> 90kg) for 1 month, followed with a progressive decrease of 10 mg Prednisone every 15 days until a dose of 10mg per day during 15 days (= stop).
Patients will take perfusion of placebo (G5%: 100ml over 30 minutes per day) for 3 days.
Efficacy of treatments
Major Cardiovascular Events (MACE) and/or persistence of left ventricular dysfunction defined as LVEF \< 50% and/or Global Longitudinal Strain (GLS) \< - 16%. MACE is a combined criterion that includes all-cause mortality, heart failure hospitalization, sustained ventricular arrhythmia, heart transplantation or assistance and recurrent acute myocarditis with LV dysfunction.
Time frame: 6 months
Changes in LVEF ≥ 50%
Changes in LVEF ≥ 50% at 6 months using 2D trans-thoracic echocardiography (2D-TTE)
Time frame: 6 months
Global Longitudinal Strain (GLS) ≥ -16%
Changes in Global Longitudinal Strain (GLS) ≥ -16% at 6 months using 2D-TTE
Time frame: 6 months
All-cause mortality
Occurred of a death
Time frame: 6 months
Heart failure hospitalization
Occurred of hospitalization for heart failure
Time frame: 6 months
Sustained ventricular arrhythmia
Occurred of sustained ventricular arrhythmia
Time frame: 6 months
Heart transplantation
Occurred of heart transplantation
Time frame: 6 months
Heart assistance by extracorporeal membrane oxygenation (ECMO), Intra-aortic balloon pump (IABP), Impella® device or Left Ventricular Assistance Devices (LVAD)
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After the perfusion of placebo, patients will take by oral Prednisone placebo once a day for the same duration as that required if the patient was in the investigational medicinal products group (1 month + progressive decrease).
Need for heart assistance by extracorporeal membrane oxygenation (ECMO), Intra-aortic balloon pump (IABP), Impella® device or Left Ventricular Assistance Devices (LVAD)
Time frame: 6 months
Recurrence of acute myocarditis with LV dysfunction
Time to recurrence of acute myocarditis with LV dysfunction
Time frame: 6 months
Safety of the treatment regimens
Adverse events and serious adverse events
Time frame: 6 months
Adherence to the treatment regimen
Compliance to the treatment (premature ending of the treatment or proportion of non-administered doses of the treatment)
Time frame: 6 months
Evaluate quality of life using Minnesota living with heart failure questionnaire (MLHFQ)
Increased quality of life evaluated by Minnesota living with heart failure questionnaire during follow up. 21 questions rated from 0 to 5. Overall score from 0 to 105. The score increase with the adverse impact of heart failure.
Time frame: 6 months