METHYLPREDNISOLONE SODIUM SUCCINATE for Acute myocarditis

Inclusion criteria

• {"criterion_text":"- Age 18 years or older and below 70 years (18-69 years)\n- LVEF<50% and LV-EDD<56 mm (parasternal long-axis view) on echocardiogram\n- Increased troponin (3x URL) at the time of randomization\n- Clinically suspected myocarditis with onset of cardiac symptoms within 3 weeks from randomization;\n- Excluded coronary artery disease by coronary angiogram in subjects ≥46 years of age, in case myocarditis is not histologically proven\n- Randomization within 120 hours from hospital admission\n- Endomyocardial biopsy (EMB) is not considered necessary before randomization and performing EMB is based on the decision of the local team\n- Patient has voluntarily signed and dated an informed consent form (ICF), approved by an Ethics Committee (EC) or institutional review board (IRB), after the nature of the study has been explained and the patient has had the opportunity to ask questions."}

Exclusion criteria

• {"criterion_text":"- Known systemic autoimmune disorder or other conditions at the time of randomization where immunosuppression is 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\n- Myocarditis associated with the ongoing administration of anti-cancer immune checkpoint inhibitor (ICI) agents\n- Previously known chronic cardiac disease\n- 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\n- Known chronic infective disease, such as HIV infection or tuberculosis\n- Out of hospital cardiac arrest before randomisation\n- Contraindication for CMRI\n- Echocardiographic presence of images suggestive of other cardiac diseases (i.e. endocarditis)\n- Participants involved in another clinical trial\n- Pregnant women (known pregnancy) or POSITIVE human chorionic gonadotropin (HCG) test measures (urine/blood) for women of 18-50 years of age\n- Any other significant disease with expected life expectancy <12 months (i.e., evidence of irreversible severe brain injury) 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\n- If LVEF<41%, 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; (if LVEF 41%-<50% any NT-proBNP or BNP concentration is allowed).\n- Patients already on oral/IV chronic corticosteroid therapy or other chronic immunosuppressive therapies\n- Contraindication to corticosteroids, including history of previous (steroid) psychosis, allergies to this medication and its excipients;\n- Patients with persistent peripheral eosinophilia (persistent eosinophil count >7% of the leukocytes) or known hypereosinophilic syndrome at the time of randomization"}

Primary endpoints

• {"endpoint_text":"- The primary objective is to demonstrate an increase in the rate of the primary composite endpoint (LVEF >55% or increase of 10%) in patients treated with pulsed corticosteroid therapy vs. standard therapy and maximal supportive care.","definition_or_measurement_approach":"Primary composite endpoint defined as LVEF >55% or an absolute increase in LVEF ≥10% on echocardiogram measured after 5 days from randomization (measured by echocardiogram)."}

Secondary endpoints

• {"endpoint_text":"- The main secondary composite endpoint is defined as the reduction in the 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)","definition_or_measurement_approach":"Assessed by 6-month CMRI; CMRI clips centrally reviewed blinded by readers; endpoint is proportion with LVEF<55% and/or LV dilation at 6 months."}
• {"endpoint_text":"- Proportion of patients with LV dilation on 6-months CMRI","definition_or_measurement_approach":"Assessed by 6-month CMRI."}
• {"endpoint_text":"- Proportion of patients with LVEF<55% on 6-month CMRI","definition_or_measurement_approach":"Assessed by 6-month CMRI."}
• {"endpoint_text":"- LGE burden (% of mass) on 6 month CMRI","definition_or_measurement_approach":"Late gadolinium enhancement (LGE) burden measured as % of myocardial mass on 6-month CMRI."}
• {"endpoint_text":"- Composite endpoint defined as the time from randomization to the first event ((1) all-cause death or (2) HTx or (3) long-term LVAD implantation, or (5) first rehospitalization due to HF or ventricular arrhythmias, or advanced AV block) occurring within 6 months and 2 years","definition_or_measurement_approach":"Time-to-event composite assessed from randomization with events adjudicated within 6 months and up to 2 years."}
• {"endpoint_text":"- Mortality: Time from randomization to all-cause death within 6 months and 2 years","definition_or_measurement_approach":"Time-to-event all-cause mortality assessed within 6 months and up to 2 years from randomization."}
• {"endpoint_text":"- Time from randomization tot hospitalization for heart failure within 6 months and 2 years","definition_or_measurement_approach":"Time-to-event hospitalization for heart failure assessed within 6 months and up to 2 years."}
• {"endpoint_text":"- Composite endpoint of presence of NSVT OR burden of PVC`s>10% on 24 hour ECG ambulatory monitoring, performed at 6 months follow-up","definition_or_measurement_approach":"24-hour ambulatory ECG (Holter) at 6 months; endpoint defined as presence of NSVT or PVC burden >10%."}
• {"endpoint_text":"- Burden of PVCs (% of total heart beats) on 24 hour holtermonitoring, performed at 6 months follow-up","definition_or_measurement_approach":"PVC burden measured as % of total beats on 24-hour Holter at 6 months."}
• {"endpoint_text":"- Presence of NSVT on 24 hour holtermonitoring performed at 6 months follow-up","definition_or_measurement_approach":"NSVT presence assessed on 24-hour Holter at 6 months."}
• {"endpoint_text":"- Quality of life and health assessment at 2 and 6 months follow-up using the EuroQol 5-dimension, 5 level questionnaire","definition_or_measurement_approach":"Quality of life measured using EQ-5D-5L at 2 and 6 months."}
• {"endpoint_text":"- Recurrence of acute myocarditis at six months and 2 years","definition_or_measurement_approach":"Clinical assessment/adjudication of recurrent acute myocarditis at 6 months and 2 years."}
• {"endpoint_text":"- Hospitalization due to recurrence of AM, pericarditis or recurrence of chest pain or atrial fibrillation","definition_or_measurement_approach":"Hospitalization events for listed causes recorded during follow-up."}
• {"endpoint_text":"- In-hospital composite endpoint, 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.","definition_or_measurement_approach":"Composite assessed during index hospitalization; proportion experiencing any listed events."}
• {"endpoint_text":"- relative reduction of troponin levels after 5 days from randomization","definition_or_measurement_approach":"Change in troponin levels measured at baseline and at 5 days post-randomization; relative reduction calculated."}
• {"endpoint_text":"- Reduction in heart rate on ECG after 3 days from randomization","definition_or_measurement_approach":"ECG heart rate measured at baseline and at 3 days; change recorded."}
• {"endpoint_text":"- increase in LVEF on echocardiogram after 5 days from randomization","definition_or_measurement_approach":"Echocardiographic LVEF measured at baseline and at 5 days post-randomization; change recorded."}
• {"endpoint_text":"- Number of days in the hospital","definition_or_measurement_approach":"Length of initial hospital stay recorded in days."}
• {"endpoint_text":"- number of days on the ICU","definition_or_measurement_approach":"Number of ICU days recorded during index hospitalization."}
• {"endpoint_text":"- Need for inotropes","definition_or_measurement_approach":"Requirement for inotropic therapy during hospitalization recorded (yes/no and duration)."}
• {"endpoint_text":"- number of days on t-MCS","definition_or_measurement_approach":"Number of days on temporary mechanical circulatory support recorded."}

Belgium

Earliest CTIS Part Ii Submission Date

15-01-2024

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

781

Number Of Sites

5

Number Of Participants

40

Italy

Earliest CTIS Part Ii Submission Date

14-01-2024

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

782

Number Of Sites

16

Number Of Participants

100

Slovenia

Earliest CTIS Part Ii Submission Date

20-02-2024

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

745

Number Of Sites

1

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

652

Number Of Sites

3

Number Of Participants

50

Primary sponsor

Full Name

Antwerp University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium