Treatment of acute myocarditis with corticosteroids

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

This study is testing if a corticosteroid treatment can help people with acute myocarditis and heart function issues feel better compared to standard care.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 174 (estimated)
• Ages: 18 Years to 69 Years
• Sex: All
• Sponsor: University Hospital, Antwerp (Academic / other)
• Locations: 19 sites (Edegem, Antwerp and 18 other locations)
• Trial ID: NCT05974462 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of pulsed intravenous methylprednisolone compared to standard therapy in patients with acute myocarditis and mildly reduced left ventricular ejection fraction (LVEF). Participants will be randomly assigned to receive either the corticosteroid treatment or standard care, with the primary outcomes being improvements in LVEF and reductions in adverse cardiac events over a six-month period. The study aims to determine if corticosteroids can effectively reduce myocardial inflammation and improve heart function in this patient population.

Who should consider this trial

Good fit: Ideal candidates are patients with acute myocarditis, LVEF less than 50%, and recent onset of cardiac symptoms.

Not a fit: Patients with known systemic autoimmune disorders or those requiring immunosuppression for other conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve heart function and reduce complications in patients with acute myocarditis.

How similar studies have performed: While the use of corticosteroids in myocarditis is a common consideration, this specific approach has not been extensively tested in prior studies, making it a novel investigation.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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;
* 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);
* Contraindication to corticosteroids, including allergies to this medication and its excipients;
* 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;
* Myocarditis associated with the ongoing administration of anti-cancer immune checkpoint inhibitor (ICI) agents;
* 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);
* 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;
* Out-of-hospital cardiac arrest;
* 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 (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.
* 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).

Where this trial is running

Edegem, Antwerp and 18 other locations

• Antwerp University Hospital — Edegem, Antwerp, Belgium (Recruiting)
• Onze-Lieve-Vrouwziekenhuis (OLV ziekenhuis) — Aalst, Belgium (Recruiting)
• Middelheim Ziekenhuis — Antwerp, Belgium (Recruiting)
• Jessa ziekenhuis — Hasselt, Belgium (Recruiting)
• Universitair ziekenhuis Leuven — Leuven, Belgium (Recruiting)
• Niguarda Hospital — Milan, Milan, Italy (Recruiting)
• Azienda USL Toscane SUD Est — Arezzo, Italy (Not_yet_recruiting)
• Azienda Ospedaliera Papa Giovanni XXIII — Bergamo, Italy (Not_yet_recruiting)
• ASST Spedali Civili di Brescia — Brescia, Italy (Not_yet_recruiting)
• Careggi University Hospital — Florence, Italy (Not_yet_recruiting)
• Alessandro Manzoni hospital — Lecco, Italy (Not_yet_recruiting)
• San Raffaele Hospital — Milan, Italy (Not_yet_recruiting)
• Ospedale Maggiore di Milano — Milan, Italy (Not_yet_recruiting)
• Fondazione IRCCS Policlinico San Matteo — Pavia, Italy (Not_yet_recruiting)
• Fondazione Toscana Gabriele Monasterio — Pisa, Italy (Not_yet_recruiting)
• Policlinico Universitario Agostino Gemelli — Roma, Italy (Not_yet_recruiting)
• Azienda Sanitaria Universitaria Friuli Centrale — Udine, Italy (Not_yet_recruiting)
• University Medical Centre of Ljubljana — Ljubljana, Slovenia (Recruiting)
• Hospital Universitario A Coruña (CHUAC) — A Coruña, Spain (Not_yet_recruiting)

Study contacts

• Principal investigator: Caroline Van de Heyning — University Hospital, Antwerp
• Study coordinator: Caroline Van De Heyning, MD PhD

Conditions Acute Myocarditis