Evaluation of High-Dose Pulse Intravenous Methylprednisolone Sodium Succinate in Patients with Complicated Fulminant Acute Myocarditis

The primary objective of this study is to demonstrate a reduction in the rate of the primary composite endpoint in patients with **complicated/fulminant acute myocarditis** treated with high-dose pulse intravenous corticosteroid therapy compared to those receiving standard therapy and maximal supportive care. This objective is clinically relevant as it aims to establish the efficacy of corticosteroid therapy in reducing severe cardiac inflammation, potentially improving patient outcomes and survival rates.

The main secondary objectives are to demonstrate a reduction in the rate of the main secondary composite endpoint in patients treated with pulsed corticosteroid therapy versus standard therapy and maximal supportive care. This evaluation is crucial for understanding the broader impact of corticosteroid therapy on secondary clinical outcomes, which may include measures of cardiac function, symptom relief, and quality of life.

The clinical trial involves a total of **one participant** diagnosed with **severe cardiac inflammation**. The study population includes both male and female subjects, aged between 18 and 69 years. Participants are required to have acute heart failure with clinically suspected acute myocarditis, indicated by specific biomarker levels, and a left ventricular ejection fraction below 41%. The trial excludes individuals with coronary artery disease unless myocarditis is histologically confirmed. Participants must have experienced the clinical onset of cardiac symptoms within three weeks prior to randomization and must be randomized within 120 hours of hospital admission. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are mentioned. The sponsor has not provided additional information regarding the selection process or other demographic details of the trial population.

The clinical trial is designed as a **single-blind**, randomized, controlled study to evaluate the safety and efficacy of high-dose pulse intravenous corticosteroid therapy in patients with complicated or fulminant **acute myocarditis**. The trial aims to demonstrate a reduction in the rate of the primary composite endpoint in patients treated with pulsed corticosteroid therapy compared to those receiving standard therapy and maximal supportive care. The study will involve two main pharmaceutical products: **Sodium Chloride** solution for infusion and **Methylprednisolone Sodium Succinate** solution for injection, administered via intravenous routes. The trial is expected to commence recruitment on June 11, 2024, and conclude by December 31, 2028.

Participants will be involved in the study for a maximum treatment period of three days, with the primary endpoint being the time from randomization to the first event occurring within six months. The inclusion criteria specify that participants must be aged between 18 and 69 years, with acute heart failure and clinically suspected acute myocarditis, among other specific clinical parameters. The exclusion criteria are not explicitly detailed in the provided data. The trial will include several study visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Randomization must occur within 120 hours of hospital admission.

Follow-up visits will be scheduled to monitor the participants' health status and collect data on primary and secondary endpoints, such as mortality rates, rehospitalization due to heart failure or ventricular arrhythmias, and changes in left ventricular ejection fraction. The end-of-study visit will occur at the six-month mark to assess the final outcomes and gather comprehensive data for analysis. Participants may be withdrawn from the study if they experience adverse events that necessitate discontinuation of the treatment or if they fail to comply with the study protocol. The trial's design ensures rigorous monitoring and data collection to achieve its objectives while maintaining participant safety and scientific integrity.

The clinical trial involves the administration of **Sodium Chloride** as a non-experimental treatment. The product, marketed under the name "Sodio cloruro Fresenius Kabi Italia 0,9%, soluzione per infusione," is provided in the form of a **solution for infusion**. The active substance, sodium chloride, is of chemical origin. The solution is administered via **intravenous infusion**. The maximum daily dose is 250 ml, with a total maximum dose of 750 ml over a treatment period of up to 3 days. This product is manufactured by Fresenius Kabi Italia S.R.L. and is classified under the ATC code B05BB01, which pertains to electrolytes.

The experimental treatment in this trial is **Methylprednisolone Sodium Succinate**, marketed as "SOLU MEDROL 1000 mg/15,6 ml polvere e solvente per soluzione iniettabile." This product is a **solution for injection** and is also of chemical origin. The administration route is **intravenous use**. The maximum daily dose is 1000 mg, with a total maximum dose of 3000 mg over a treatment period of up to 3 days. This product is manufactured by Pfizer Italia S.R.L. and is classified under the ATC code H02AB04, which pertains to methylprednisolone. The trial aims to assess the safety and efficacy of high-dose pulse intravenous corticosteroid therapy in treating patients with complicated or fulminant acute myocarditis.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary composite endpoint is defined as the time from randomization to the first event occurring within six months, which includes all-cause death, heart transplantation (HTx), long-term left ventricular assist device (LVAD) implant, need for an upgrading of the temporary mechanical circulatory support (t-MCS), ventricular tachycardia (VT) or fibrillation (VF) treated with direct current (DC) shock, and first rehospitalization due to heart failure (HF) or ventricular arrhythmias, or advanced atrioventricular (AV) block.

Secondary endpoints include the time from randomization to the first event occurring within six months among all-cause death, HTx, long-term LVAD implant, and first rehospitalization due to HF or ventricular arrhythmias, or advanced AV block. Additional secondary endpoints are mortality within six months, in-hospital composite endpoint during index hospitalization, number of days on t-MCS, number of days in the intensive care unit (ICU), increase in left ventricular ejection fraction (LVEF) on echocardiogram after five days, relative reduction of troponin levels after five days, reduction in heart rate (HR) on electrocardiogram (ECG) after three days, and the proportion of patients with LVEF less than 55% and/or left ventricular dilation on six-month cardiac magnetic resonance imaging (CMRI). ECHO and CMRI clips will be centrally reviewed in a blind fashion by readers to ensure objective assessment.