METHYLPREDNISOLONE for Fulminant myocarditis

Inclusion criteria

• {"criterion_text":"-\t1.\tFulminant myocarditis defined by •\tthe acute illness (<1 month from symptom onset), •\themodynamic compromise due to cardiogenic shock or electrical storm, •\televated plasma cardiac troponin > twice normal value •\tneed for hemodynamic support (inotropes or temporary mechanical circulatory support) for less than 72 hours in the absence of an ischemic cause or other pre-existing cardiomyopathies Noticeably, a coronary angiogram should be performed in patients ≥40 years of age when myocarditis has not been proven histologically. Besides, an endomyocardial biopsy will not be mandatory to fulfill the definition of fulminant myocarditis."}
• {"criterion_text":"-\t2.\tSigned informed consent from the patient, a close relative or surrogate or a family member or a legal representative for minor patient. •\tAdult : According to the specifications of emergency inclusion, randomization without the close relative/surrogate consent could be performed if the patientis unable to give his/her consent and when the close relative/surrogate/family member are absent. Close relative/surrogate/family member consent will be asked as soon as possible after randomization. The patient will be asked as soon as possible to give his/her consent for the continuation of the trial when his/her condition will allow. •\tMinor : According to the specifications of emergency inclusion, randomization could be performed when legal representative are absent. Legal representative consent will be asked as soon as possible after randomization"}
• {"criterion_text":"-\t3.\tSocial security registration (AME excluded)"}

Exclusion criteria

• {"criterion_text":"-\t1.\tAge <15"}
• {"criterion_text":"-\t10.\tPatient moribund on the day of randomization, SAPS II >90"}
• {"criterion_text":"-\t11.\tContraindication or allergies to corticosteroids or immunoglobulins or any components of the formulations or their excipients"}
• {"criterion_text":"-\t12.\tPatients already on corticosteroids or receiving IVIG"}
• {"criterion_text":"-\t13.\tParticipation in another interventional study or being in the exclusion period at the end of a previous study."}
• {"criterion_text":"-\t2.\tPregnancy or breastfeeding or baby delivery <6 months"}
• {"criterion_text":"-\t3.\tInitiation of inotropes or temporary mechanical circulatory support >72 hours"}
• {"criterion_text":"-\t4.\tResuscitation >20 minutes (cumulative low-flow time > 20 minutes )"}
• {"criterion_text":"-\t5.\tPre-existing ischemic or dilated cardiomyopathy"}
• {"criterion_text":"-\t6.\tKnown systemic autoimmune disorder or other conditions requiring immunosuppression"}
• {"criterion_text":"-\t7.\tPatients with peripheral eosinophilia (≥1000 G/L)"}
• {"criterion_text":"-\t8.\tMyocarditis associated with anti-cancer immune checkpoint inhibitor agents"}
• {"criterion_text":"-\t9.\tActive severe bacterial or fungal infectious disease"}

Primary endpoints

• {"endpoint_text":"-\tA hierarchical composite outcome assessed at day 28 of mortality or heart transplantation/VAD/persisting t-MCS and the number of days alive without t-MCS and inotropes within the 28 days following randomization","definition_or_measurement_approach":"Assessed at day 28: hierarchical composite of mortality or heart transplantation/long-term ventricular assist device (VAD)/persisting temporary mechanical circulatory support (t-MCS), and the number of days alive without t-MCS and inotropes within 28 days following randomization."}

Secondary endpoints

• {"endpoint_text":"Mortality at day 28/60/90","definition_or_measurement_approach":"All-cause mortality measured at days 28, 60 and 90 after randomization."}
• {"endpoint_text":"-\tVAD or/and heart transplant at day 28/60/90","definition_or_measurement_approach":"Occurrence of ventricular assist device implantation and/or heart transplantation assessed at days 28, 60 and 90."}
• {"endpoint_text":"-\tNumber of t-MCS-free days at day 28","definition_or_measurement_approach":"Number of days without temporary mechanical circulatory support within the first 28 days post-randomization."}
• {"endpoint_text":"-\tNumber of inotropes-free days at day 28","definition_or_measurement_approach":"Number of days without inotropic support within 28 days post-randomization."}
• {"endpoint_text":"-\tTime to improvement in left ventricular function assessed by echocardiography at D3/D7/D14/D28 following randomization","definition_or_measurement_approach":"Time to documented improvement in LV function evaluated by echocardiography at days 3, 7, 14 and 28."}
• {"endpoint_text":"-\tTime to normalize troponin and N-terminal pro–B-type natriuretic peptide within 14 days after randomization","definition_or_measurement_approach":"Time to normalization of cardiac biomarkers (troponin and NT-proBNP) within 14 days of randomization."}
• {"endpoint_text":"-\tIncidence of drugs side effects (nosocomial infections, significant gastrointestinal bleeding, renal insufficiency, acute delirium leading to the use of neuroleptic agents)","definition_or_measurement_approach":"Incidence of specified adverse events collected during hospitalization and follow-up (nosocomial infections, significant GI bleeding, renal insufficiency, acute delirium requiring neuroleptics)."}
• {"endpoint_text":"-\tProportion of patients with left ventricular ejection fraction (LVEF) < 55% and/or left ventricular dilatation at 28-day","definition_or_measurement_approach":"Proportion of patients with LVEF <55% and/or LV dilatation measured at day 28."}
• {"endpoint_text":"-\tProportion of patients with at least one episode of ventricular arrhythmia at day-28","definition_or_measurement_approach":"Proportion with ≥1 ventricular arrhythmia episode assessed up to day 28."}
• {"endpoint_text":"-\tProportion of patients with at least one episode of atrioventricular block (degree II and III) or sinoatrial, atrioventricular or intraventricular block","definition_or_measurement_approach":"Proportion with ≥1 episode of AV block (degree II/III) or other conduction blocks during follow-up (timepoint not further specified)."}
• {"endpoint_text":"-\tThe proportion of patients with LVEF<55%, left ventricular dilatation, and late gadolinium enhancement at 6 months evaluated by cardiac magnetic resonance imaging","definition_or_measurement_approach":"Proportion of patients with LVEF <55%, LV dilatation and late gadolinium enhancement assessed by cardiac MRI at 6 months."}

Methods

• Identification and recruitment of eligible patients hospitalized in intensive care units or emergency cardiology departments at participating hospitals in France (site-based hospital recruitment).
• Emergency inclusion procedure: randomization may occur in emergency situations when legal representatives or close relatives are absent; consent from the relative/legal representative and patient (when able) will be sought as soon as possible following randomization.

France

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

09-01-2025

Processing Time Days

73

Number Of Sites

8

Number Of Participants

120

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France