MYTHS-MR Trial (MYocarditis THerapy With Steroids in Patients With Mildly Reduced Ejection Fraction)

Trial details

Who runs it

University Hospital, Antwerp

Trial code

NCT05974462EU 2022-501547-33-01

Record updated

17 April 2025

Original description

The goal of this clinical trial is to demonstrate the efficacy of pulsed intravenous methylprednisolone in a single-blind randomized controlled trial versus standard therapy in patients with acute myocarditis and a mildly reduced LVEF.Read full original descriptionShow less

Single-blind, Investigator-initiated, Randomized, Controlled Trial to Assess the Safety and Efficacy of Intravenous Corticosteroid Therapy to Treat Patients With Acute Myocarditis With Mildly Reduced Left Ventricular Ejection Fraction

The goal of this clinical trial is to demonstrate the efficacy of pulsed intravenous methylprednisolone in a single-blind randomized controlled trial versus standard therapy in patients with acute myocarditis and a mildly reduced LVEF.

The main question[s] it aims to answer are:

* is there an increase in LVEF (≥55% or an absolute increase in LVEF ≥ 10%) on echocardiogram after 5 days from randomization in patients treated with pulsed corticosteroid therapy vs. standard therapy? * is there a reduction in the proportion of patients with LVEF < 55% AND/OR LV dilation on a 6-month CMRI in patients treated pulsed corticosteroid therapy vs. standard therapy? * To assess the effect of corticosteroids on the occurrence of the combined endpoint(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.

Participants will be randomized in two arms in a 1:1 ratio. The experimental group will receive pulsed corticosteroid therapy on top of the standard therapy and patients in the placebo group will be treated with a saline solution on top of their standard therapy. All other tests are executed according to standard of care.

Inclusion: LVEF<50% and LV-EDD<56 mm (parasternal long-axis view) on echocardiogram; Increased troponin (3x URL) at the time of randomization; Clinical onset of cardiac symptoms within 3 weeks from randomization; Excluded coronary artery disease by coronary angiogram in subjects ≥46 years of age, in case myocarditis is not histologically proven; Randomization within 120 hours from hospital admission; Endomyocardial biopsy (EMB) is not considered necessary before randomization and performing EMB is based on the decision of the local team.

Exclusion: 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); Previously known chronic cardiac (i.e., previous cardiomyopathy, that does NOT include previous myocarditis if there is a functional recovery at the time of screening); 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; Contraindication to corticosteroids, including allergies to this medication and its excipients; Myocarditis associated with the ongoing administration of anti-cancer immune checkpoint inhibitor (ICI) agents; Known chronic infective disease, such as HIV infection or tuberculosis; Out-of-hospital cardiac arrest; Echocardiographic presence of images suggestive of other cardiac diseases (i.e. endocarditis); 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; Patients with persistent peripheral eosinophilia (persistent 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; 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; 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); Pregnant women (known pregnancy) or POSITIVE human chorionic gonadotropin (HCG) test measures (urine/blood) for women of 18-50 years of age; Participants involved in another clinical trial.

ClinicalTrials.gov NCT05974462 · EU CTIS 2022-501547-33-01