Complicated/fulminant acute myocarditis MedDRA version: 20.0 Level: LLT Classification code 10000932 Term: Acute myocarditis System Organ Class: 100000004849
Conditions
Interventions
Product Name: Metilprednisolone
Product Code: [Metilprednisolone]
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: METILPREDNISOLONE
Current Sponsor code: Metilp
Sponsors
AZIENDA OSPEDALIERA AO OSPEDALE NIGUARDA CA' GRANDA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18 years or older and below 70 years (18-69 years) - Acute HF with clinically suspected acute myocarditis based on an N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration of 1600 pg/mL or more or a B-type natriuretic peptide (BNP) concentration of 400 pg/mL or more; - Left ventricular ejection fraction (LVEF)=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: - Known systemic autoimmune disorder at the time of randomization where corticosteroids are assumed useful. Patients in whom a systemic autoimmune disorder will be diagnosed during hospitalization will be included in the study if randomized, including patients with a diagnosis of cardiac sarcoidosis or GCM). Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis; - Patients already on oral/IV chronic corticosteroid therapy or other chronic immunosuppressive therapies (colchicine or nonsteroidal anti-inflammatory drugs [NSAIDs] are not considered immunosuppressive drugs); - Patients with peripheral eosinophilia (Eosinophil count >7% of the leukocytes) or known hypereosinophilic syndrome at the time of randomization. Patients in whom eosinophilic myocarditis will be diagnosed on EMB will be included in the study if already randomized. Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis; - Myocarditis associated with the ongoing administration of anti-cancer immune checkpoint inhibitor (ICI) agents; - Previously known chronic cardiac disease (i.e., previous cardiomyopathy); - Evidence of active bacterial or fungal infectious disease (presence of fever or increased C-reactive protein are not considered exclusion criteria), or suspected bacterial/fungal infection associated with increased levels of procalcitonin (cut-off >10 ng/mL), if the laboratory exam is available in the center; - Known chronic infective disease, such as HIV infection or tuberculosis; - Cardiac arrest before randomization or occurrence of out-of-hospital cardiac arrest; - t-MCS instituted more than 48 hours before randomization; - Patients clinically judged too sick to initiate t-MCS (i.e., irreversible multiorgan failure); - Echocardiographic presence of images suggestive of other cardiac diseases (i.e. endocarditis) - Participants involved in another clinical trial; - Pregnant women (known pregnancy) or POSITIVE human chorionic gonadotropin (HCG) test measures (urine/blood) for women of 18-50 years of age. - Any other significant disease with expected life expectancy <12 months or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate a reduction in the rate of the primary composite endpoint on patients treated with pulsed corticosteroid therapy vs. standard therapy and maximal supportive care.;Secondary Objective: The main secondary objectives are to demonstrate a reduction in the rate of the main secondary composite endpoint on patients treated pulsed corticosteroid therapy vs. standard therapy and maximal supportive care. For all other secondary endpoints, the aim is to assess the superiority of pulsed corticosteroid therapy vs. placebo on top of standard therapy and maximal supportive care.;Primary end point(s): The Primary composite endpoint is defined as the time from randomization to the first event occurring within 6 months among: (1) all-cause death, or (2) HTx, or (3) long-term LVAD implant, or (4) need for an upgrading of the t-MCS, or (5) a ventricular tachycardia (VT)/fibrillation (VF) treated with direct current (DC) shock (excluding VT/VF in patients on t-MCS other than IABP), or (6) first rehospitalization due to HF or ventricular arrhythmias, or advanced AV block.;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The main secondary composite endpoint is defined as the time from randomization to the first event occurring within 6 months among: (1) all-cause death or (2) HTx or (3) long-term LVAD implant or (4) first rehospitalization due to HF or ventricular arrhythmias, or advanced AV block. 2. Secondary composite endpoint is defined as the time from randomization to the first event occurring within 6 months among: (1) all-cause death or (2) heart transplantation (HTx) or (3) long-term left ventricular assist device (LVAD) implant. 3. Mortality: time from randomization to all-cause death within 6 months. 4. In-hospital composite endpoint is defined as the proportion of patients who experience at least one of the following events during index hospitalization: (1) all-cause death, or (2) HTx, or (3) long-term LVAD implant, or (4) need for an upgrading of the t-MCS, or (5) a VT/VF treated with DC shock (excluding VT/VF in patients on t-MCS other than IABP). 5. Number of days on t-MCS from randomization. 6. Number of days in ICU from randomization. 7. Increase in LVEF on echocardiogram after 5 days from randomization (ECHO clips will be centrally reviewed in a blind fashion by readers). 8. Relative reduction of troponin levels after 5 days from randomization (ratio of troponin level/local troponin URL). 9. Reduction in heart rate (HR) on ECG after 3 days from randomization (ECG recorded at the hour of initial randomization - ECGs will be centrally reviewed in a blind fashion by readers). 10. Proportion of patients with LVEF<55% AND/OR LV dilation on 6-month cardiac magnetic resonance imaging (CMRI) (CMRI clips will be centrally reviewed in a blind fashion by readers). 11. Proportion of patients with LVEF<55% on 6-month CMRI (CMRI clips will be centrally reviewed in a blind fashion by readers). 12. Proportion of patients with LV dilation on 6-month CMRI (CMRI clips will be centrally reviewed in a blind fashion by readers).; The following safety endpoint | — |
Countries
Belgium, Finland, France, Italy, Japan, Spain, Sweden, United States
Contacts
Public ContactStruttura Complessa Cardiologia 2 -
ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA
Outcome results
None listed