Methylprednisolone for Acute myocarditis

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- Written signed informed consent"}
• {"criterion_text":"- Affiliation to the French health care system (Sécurité Sociale) or to another social protection scheme with the exception of State Medical Aid (Aide Médicale de l’Etat AME)"}
• {"criterion_text":"- Active myocarditis defined by (all items are required): 1- Chest pain and/or heart failure and/or syncope and/or sustained ventricular arrhythmias and/or aborted sudden death and/or cardiogenic shock and/or ECG modification (atrioventricular block or bundle branch block or sinus arrest or ST or T waves change or ventricular arrhythmia or atrial fibrillation or abnormal Q waves), 2- And troponin rise (1,5 times the normal range) and 3- And diagnosis of active myocarditis on Cardiac Magnetic Resonance (according to Lake-Louise criteria) or by histological evidence on endomyocardial biopsy (Dallas’s criteria)"}
• {"criterion_text":"- Left-ventricular dysfunction defined as LVEF < 50% and/or GLS < -16% assessed with 2D-TTE"}
• {"criterion_text":"- Normal coronary angiography or CT Scan (without stenosis > 50%) during the previous year"}

Exclusion criteria

• {"criterion_text":"- Active coronary disease"}
• {"criterion_text":"- Other auto-immune or inflammatory disease requiring corticosteroids treatment within 6 months before enrolment"}
• {"criterion_text":"- Pregnancy or breastfeeding"}
• {"criterion_text":"- Woman of childbearing potential without effective method of birth control"}
• {"criterion_text":"- Contra-indication linked to auxiliary drugs according to respective SmPC"}
• {"criterion_text":"- Patient deprived of liberty or under Curatorship/Tutorship, safeguard of justice, according to French law"}
• {"criterion_text":"- According to the opinion of the investigator, foreseeable inability to respect the protocol (understanding of research, ability to go to hospital, ability to take oral treatment, etc."}
• {"criterion_text":"- Patient not speaking or understanding French"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Any medical and/or cognitive condition which limits the ability of participant to participate in study"}
• {"criterion_text":"- Contra-indication linked to steroids (Methylprednisolone and Prednisone) according to SmPC: 1- Any infectious condition excluding the specified therapeutic indications of Methylprednisolone and Prednisone, 2- Certain evolving viruses (notably hepatitis, herpes, chickenpox, shingles), 3- Psychotic states not yet controlled by treatment, 4- Recent live vaccines or live attenuated vaccines in patients receiving dosages greater than 20 mg/day of prednisone equivalent for more than two weeks and during the 3 months following the cessation of corticosteroid therapy (risk of generalized vaccine disease possibly fatal), 5- Hypersensitivity to the active substances or to any of the excipients"}
• {"criterion_text":"- Other causes of chronic heart failure (coronary artery disease, primary valvular heart disease, congenital heart disease)"}
• {"criterion_text":"- Other etiology of myocarditis requiring corticosteroids treatment as giant cells myocarditis, eosinophilic myocarditis and cardiac sarcoidosis or immune checkpoint inhibitor myocarditis"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Persistence of LV dysfunction defined by LVEF < 50% and/or GLS < -16% between baseline (D-2) and 6 months (M6). MACE is a composite endpoint including all-cause mortality, heart failure hospitalization, sustained ventricular arrhythmia, heart transplantation or mechanical assistance, and recurrent acute myocarditis with LV dysfunction at 6 months."}

Secondary endpoints

• {"endpoint_text":"- Changes in LVEF ≥ 50% at 6 months using 2D trans-thoracic echocardiography (2D-TTE) between baseline (D-2 maximum) and 6 months (M6)","definition_or_measurement_approach":"Measured by 2D transthoracic echocardiography (2D-TTE) comparing baseline (D-2 maximum) and 6 months (M6)."}
• {"endpoint_text":"- Changes in Global Longitudinal Strain (GLS) ≥ -16% at 6 months using 2D-TTE between baseline (D-2 maximum) and 6 months (M6)","definition_or_measurement_approach":"Measured by 2D-TTE GLS comparing baseline (D-2 maximum) and 6 months (M6)."}
• {"endpoint_text":"- All-cause mortality","definition_or_measurement_approach":"Death from any cause during follow-up."}
• {"endpoint_text":"- Hospitalization for heart failure","definition_or_measurement_approach":"Hospital admission for heart failure during follow-up."}
• {"endpoint_text":"- Sustained ventricular arrhythmia","definition_or_measurement_approach":"Occurrence of sustained ventricular arrhythmia during follow-up (as captured in clinical records)."}
• {"endpoint_text":"- Heart transplantation","definition_or_measurement_approach":"Receipt of heart transplant during follow-up."}
• {"endpoint_text":"- Heart assistance by extracorporeal membrane oxygenation (ECMO), Intra-aortic balloon pump (IABP), Impella device or Left Ventricular Assistance Devices (LVAD)","definition_or_measurement_approach":"Use of listed mechanical circulatory support devices during follow-up."}
• {"endpoint_text":"- Time to recurrence of acute myocarditis with LV dysfunction","definition_or_measurement_approach":"Time from randomization to documented recurrence of acute myocarditis with LV dysfunction."}
• {"endpoint_text":"- Adverse events and serious adverse events especially nosocomial infectious and duration of treatment by insulin","definition_or_measurement_approach":"Safety monitoring of AEs/SAEs, with specific attention to nosocomial infections and insulin treatment duration."}
• {"endpoint_text":"- Compliance to the treatment (premature ending of the treatment or proportion of non-administered doses of the treatment)","definition_or_measurement_approach":"Assessment of treatment adherence (premature discontinuation or proportion of missed doses)."}
• {"endpoint_text":"- Increased quality of life evaluated by Minnesota living with heart failure questionnaire (MLHFQ) during follow up","definition_or_measurement_approach":"Quality of life measured using the MLHFQ at follow-up visits."}

France

Earliest CTIS Part Ii Submission Date

29-11-2024

Latest Decision Or Authorization Date

04-08-2025

Processing Time Days

248

Number Of Sites

26

Number Of Participants

420

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France