MYTHS - MYocarditis THerapy With Steroids

NCT05150704 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: MYTHS
• Study Type: interventional
• Target: 288
• Locations: 9 countries
• Sites: 49

Brief Summary

This is a phase III, multi-center international, single blind randomized controlled trial to test the efficacy of pulsed intravenous (IV) methylprednisolone versus standard therapy on top of maximal support in patients with Acute myocarditis (AM).

Conditions

Myocarditis Acute

Keywords

Acute Myocarditis; Corticosteroid therapy; Myocarditis; Trial; Immunosuppression; Acute heart failure; Fulminant acute myocarditis

Outcome Measures

Primary Outcomes (1)

• Time from randomization to the first event among: all-cause death, HTx, long-term LVAD implant, need for an upgrading of the t-MCS, VT/VF treated with DC shock, first rehospitalization due to HF or ventricular arrhythmias, or AV block.

  The Primary composite endpoint is defined as the time from randomization to the first event occurring within 6 months on patients treated with pulsed corticosteroid therapy vs. standard therapy and maximal supportive care, among: (1) all-cause death, or (2) heart transplantation (HTx), or (3) long-term left ventricular assist device (LVAD) implant, or (4) need for an upgrading of the t-MCS, or (5) a ventricular tachycardia (VT)/fibrillation (VF) treated with direct current (DC) shock (excluding VT/VF in patients on t-MCS other than IABP), or (6) first rehospitalization due to HF or ventricular arrhythmias, or advanced Atrioventricular (AV) block.

  6 months from patients enrollment

Secondary Outcomes (11)

• Time from randomization to the first event among: all-cause death, HTx, long-term LVAD implant, first rehospitalization due to HF or ventricular arrhythmias, or advanced AV block.

  6 months from patients enrollment

• Mortality

  6 months from patients enrollment

• 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

  6 months from patients enrollment

• Number of days on t-MCS from randomization

  6 months from patients enrollment

• Number of days in ICU from randomization

  6 months from patients enrollment

Other Outcomes (1)

• Safety endpoints

  6 months from patients enrollment

Study Arms (2)

Experimental arm

EXPERIMENTAL

Pulsed corticosteroid therapy (methylprednisolone 1 g IV qd for 3 days diluted in saline solution 250 mL) on top of standard therapy and maximal supportive care

Drug: Methylprednisolone

Control arm

PLACEBO COMPARATOR

Placebo (saline solution 250 mL IV qd for 3 days) on top of standard therapy and maximal supportive care.

Drug: saline solution

Interventions

Methylprednisolone DRUG

Pulsed corticosteroid therapy (methylprednisolone 1 g IV qd for 3 days diluted in saline solution 250 mL) on top of standard therapy and maximal supportive care

Experimental arm

saline solution DRUG

Placebo (saline solution 250 mL IV qd for 3 days) on top of standard therapy and maximal supportive care.

Control arm

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted to hospital for suspected AM
• Age 18 years or older and below 70 years (18-69 years)
• Acute HF with clinically suspected acute myocarditis based on 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;
• Left ventricular ejection fraction (LVEF)\<41% and left ventricular end diastolic diameter (LV-EDD)\<56 mm (parasternal long-axis view) on echocardiogram;
• Increased troponin (3x upper reference limit \[URL\]) 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.

You may not qualify if:

• 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 giant cell myocarditis (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 of a systemic autoimmune disorder, or cardiac sarcoidosis or GCM;
• 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 endomyocardial biopsy (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 disease (i.e., previous cardiomyopathy) that does NOT include previous myocarditis if there is a functional recovery at the time of screening);
• Known chronic infective disease, such as HIV infection or tuberculosis;
• out-of-hospital cardiac arrest;
• t-MCS instituted more than 48 hours before randomization;
• Patients clinically judged too sick to initiate t-MCS (i.e., irreversible multiorgan failure);
• 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.

Sponsors & Collaborators

• Niguarda Hospital: lead
• Ministry of Health, Italy: collaborator
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator
• University of Milano Bicocca: collaborator
• Regione Lombardia: collaborator

Study Sites (49)

University of California San Diego

San Diego, California, 92093, United States

RECRUITING

University of Texas

Houston, Texas, 77204, United States

NOT YET RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

NOT YET RECRUITING

Medical University of Graz

Graz, Austria

RECRUITING

Medical University Innsbruck

Innsbruck, Austria

NOT YET RECRUITING

Medical University of Wien

Vienna, Austria

RECRUITING

Onze Lieve Vrouwziekenhuis

Aalst, Belgium

RECRUITING

Antwerp University Hospital

Edegem, Belgium

RECRUITING

Jessa Hospital Hasselt

Hasselt, Belgium

RECRUITING

University Hospitals Leuven

Leuven, Belgium

RECRUITING

Masaryk University and St. Anne's University Hospital

Brno, Czechia

RECRUITING

Charles University in Prague and General University Hospital

Prague, Czechia

RECRUITING

Institute for Clinical and Experimental Medicine - IKEM

Prague, Czechia

RECRUITING

Heart and Lung Center, Helsinki University Hospital

Helsinki, Finland

NOT YET RECRUITING

AOU Ospedali Riuniti Umberto I°-Lancisi-Salesi di Ancona

Ancona, Italy

RECRUITING

ASST Papa Giovanni XXIII

Bergamo, Italy

RECRUITING

Policlinico S.Orsola-Malpighi

Bologna, Italy

RECRUITING

ASST Spedali Civili

Brescia, Italy

RECRUITING

Azienda Ospedaliera "G.Brotzu"

Cagliari, Italy

RECRUITING

P.O. SS. Annunziata Chieti -ASL 2 Abruzzo

Chieti, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

RECRUITING

Ospedale Policlinico San Martino, IRCCS

Genova, Italy

RECRUITING

Azienda Socio-Sanitaria Territoriale (ASST) di Lecco

Lecco, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

RECRUITING

Centro Cardiologico Monzino

Milan, Italy

RECRUITING

ASST Monza, Ospedale San Gerardo

Monza, Italy

RECRUITING

Azienda Ospedaliera Specialistica dei Colli - Ospedale Monaldi

Napoli, Italy

RECRUITING

Azienda Ospedaliero Universitaria di Parma

Parma, Italy

RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

RECRUITING

Fondazione Toscana Gabriele Monasterio

Pisa, Italy

RECRUITING

Azienda Ospedaliera San Camillo Forlanini di Roma

Roma, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy

RECRUITING

Azienda Ospedaliera Universitaria Senese, Policlinico Santa Maria alle Scotte

Siena, Italy

RECRUITING

Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino

Torino, Italy

RECRUITING

Presidio Ospedaliero Universitario "Santa Maria della Misericordia"

Udine, Italy

RECRUITING

University Medical Centre Ljubljana

Ljubljana, Slovenia

RECRUITING

Complexo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, Spain

RECRUITING

Bellvitge University Hospital

Barcelona, Spain

RECRUITING

Hospital de La Santa Creu I Sant Pau

Barcelona, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Spain

RECRUITING

Hospital 12 de Octubre

Madrid, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón in Madrid

Madrid, Spain

RECRUITING

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, Spain

RECRUITING

Hospital Universitario Virgen de la Arrixaca

Murcia, Spain

RECRUITING

Sahlgrenska Universitetssjukhuset

Göthenburg, Sweden

NOT YET RECRUITING

Lund University and Skåne University Hospital

Lund, Sweden

NOT YET RECRUITING

Karolinska Universitetssjukhuset

Stockholm, Sweden

NOT YET RECRUITING

Related Publications (9)

• Ammirati E, Frigerio M, Adler ED, Basso C, Birnie DH, Brambatti M, Friedrich MG, Klingel K, Lehtonen J, Moslehi JJ, Pedrotti P, Rimoldi OE, Schultheiss HP, Tschope C, Cooper LT Jr, Camici PG. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document. Circ Heart Fail. 2020 Nov;13(11):e007405. doi: 10.1161/CIRCHEARTFAILURE.120.007405. Epub 2020 Nov 12.

  PMID: 33176455 BACKGROUND

• Kociol RD, Cooper LT, Fang JC, Moslehi JJ, Pang PS, Sabe MA, Shah RV, Sims DB, Thiene G, Vardeny O; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology. Recognition and Initial Management of Fulminant Myocarditis: A Scientific Statement From the American Heart Association. Circulation. 2020 Feb 11;141(6):e69-e92. doi: 10.1161/CIR.0000000000000745. Epub 2020 Jan 6.

  PMID: 31902242 BACKGROUND

• Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Ciro A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG; Registro Lombardo delle Miocarditi. Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry. Circulation. 2018 Sep 11;138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319.

  PMID: 29764898 BACKGROUND

• Ammirati E, Veronese G, Brambatti M, Merlo M, Cipriani M, Potena L, Sormani P, Aoki T, Sugimura K, Sawamura A, Okumura T, Pinney S, Hong K, Shah P, Braun O, Van de Heyning CM, Montero S, Petrella D, Huang F, Schmidt M, Raineri C, Lala A, Varrenti M, Foa A, Leone O, Gentile P, Artico J, Agostini V, Patel R, Garascia A, Van Craenenbroeck EM, Hirose K, Isotani A, Murohara T, Arita Y, Sionis A, Fabris E, Hashem S, Garcia-Hernando V, Oliva F, Greenberg B, Shimokawa H, Sinagra G, Adler ED, Frigerio M, Camici PG. Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction. J Am Coll Cardiol. 2019 Jul 23;74(3):299-311. doi: 10.1016/j.jacc.2019.04.063.

  PMID: 31319912 BACKGROUND

• Chen H, Liu J, Yang M. Corticosteroids for viral myocarditis. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD004471. doi: 10.1002/14651858.CD004471.pub2.

  PMID: 17054204 BACKGROUND

• Mason JW, O'Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, Moon TE. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. 1995 Aug 3;333(5):269-75. doi: 10.1056/NEJM199508033330501.

  PMID: 7596370 BACKGROUND

• Ammirati E, Cipriani M, Lilliu M, Sormani P, Varrenti M, Raineri C, Petrella D, Garascia A, Pedrotti P, Roghi A, Bonacina E, Moreo A, Bottiroli M, Gagliardone MP, Mondino M, Ghio S, Totaro R, Turazza FM, Russo CF, Oliva F, Camici PG, Frigerio M. Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis. Circulation. 2017 Aug 8;136(6):529-545. doi: 10.1161/CIRCULATIONAHA.117.026386. Epub 2017 Jun 2.

  PMID: 28576783 BACKGROUND

• Ammirati E, Moslehi JJ. Diagnosis and Treatment of Acute Myocarditis: A Review. JAMA. 2023 Apr 4;329(13):1098-1113. doi: 10.1001/jama.2023.3371.

  PMID: 37014337 BACKGROUND

• Veronese G, Nonini S, Cannata A, Aresta F, Olivieri G, Montrasio E, De Caria D, Perna E, Calini A, Bottiroli M, Cislaghi F, Pedrazzini G, Baltaro F, Quattrocchi G, Pedrotti P, Russo CF, Garascia A, Mondino M, Ammirati E. Fulminant Lymphocytic Myocarditis During Pregnancy Treated With Temporary Mechanical Circulatory Supports and Aggressive Immunosuppression. Circ Heart Fail. 2022 Dec;15(12):e009810. doi: 10.1161/CIRCHEARTFAILURE.122.009810. Epub 2022 Oct 28. No abstract available.

  PMID: 36305298 DERIVED

MeSH Terms

Conditions

Myocarditis

Interventions

Methylprednisolone; Saline Solution

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Enrico Ammirati, MD, PhD

CONTACT

+39 0264447791; enrico.ammirati@ospedaleniguarda.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single blind randomized controlled trial

Study Record Dates

• First Submitted: November 14, 2021
• First Posted: December 9, 2021
• Study Start: October 7, 2021
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9); CZ (3); SE (3); AU (3); IT (21); US (4); BE (4); FI (1); SL (1)