NCT06522100

Corticoid Therapy in Acute Myocarditis

Use of Glucocorticoids Therapy in Acute Myocarditis With Severe Left Ventricular Dysfunction: a Multicenter Randomized Controlled Trial

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 420 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Refer to the "Detailed Description" section.

Detailed 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: * 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.

Conditions

• Acute Myocarditis

Interventions

Type	Name	Description
DRUG	Intravenous administration of Methylprednisolone	Patients will take intravenous administration of Methylprednisolone (500mg/100ml by IV over 30 minutes per day) for 3 days.
DRUG	Oral Prednisone	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).
DRUG	Perfusion of placebo	Patients will take perfusion of placebo (G5%: 100ml over 30 minutes per day) for 3 days.
DRUG	Oral Prednisone placebo	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).

Timeline

• Start date: 2025-02-01
• Primary completion: 2028-08-16
• Completion: 2028-08-16
• First posted: 2024-07-26
• Last updated: 2024-07-29