Status and phase
Conditions
Treatments
About
Refer to the "Detailed Description" section.
Full description
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:
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Age ≥ 18 years
Written signed informed consent
Affiliation to the French health care system or to another social protection scheme with the exception of State Medical Aid
Active myocarditis defined by (all items are required):
Left-ventricular dysfunction defined as LVEF < 50% and/or GLS < -16% assessed with 2D-TTE
Normal coronary angiography or CT Scan (without stenosis > 50%) during the previous year
Exclusion criteria
Active coronary disease
Other causes of chronic heart failure (coronary artery disease, primary valvular heart disease, congenital heart disease)
Other etiology of myocarditis requiring corticosteroids treatment as giant cells myocarditis, eosinophilic myocarditis and cardiac sarcoidosis or immune checkpoint inhibitor myocarditis
Other auto-immune or inflammatory disease requiring corticosteroids treatment within 6 months before enrolment
Pregnancy or breastfeeding
Woman of childbearing potential without effective method of birth control (included contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices)
Patient deprived of liberty or under Curatorship/Tutorship, safeguard of justice, according to French law
Foreseeable inability, according to the investigator, to participate in all the visits, treatments and measures provided for in the protocol
Patient not speaking or understanding French
Concomitant participation in another clinical trial on medical product for human use, to a clinical investigation on a medical device, to interventional study involving human participants or in the exclusion period at the end of a previous clinical trial on medical product for human use, a clinical investigation on a medical device, or study involving human participants. Participation in non-interventional research is permitted.
Any medical and/or cognitive condition which limits the ability of participant to participate in study
Contra-indication linked to steroids (Methylprednisolone and Prednisone) according to summary of product characteristics:
Contra-indication linked to auxiliary drugs according to respective summary of product characteristics:
Primary purpose
Allocation
Interventional model
Masking
420 participants in 2 patient groups, including a placebo group
Loading...
Central trial contact
Raphäelle HUGUET, Dr; David AOUATE, Dr
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal