Study to assess the safety and efficacy of high dose pulse intravenous corticosteroid therapy to treat patients with complicated/fulminant acute myocarditis, randomly comparing this treatment with standard therapy

Phase 1

• Conditions: Complicated/fulminant acute myocarditis; MedDRA version: 20.0Level: LLTClassification code 10000932Term: Acute myocarditisSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2021-000938-34-IT
• Lead Sponsor: AZIENDA OSPEDALIERA AO OSPEDALE NIGUARDA CA' GRANDA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-07
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

- 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 72 hours from hospital admission.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 223
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

- Known systemic autoimmune disorder at the time of randomization where corticosteroids are 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);
- Patients with peripheral eosinophilia (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 disease (i.e., previous cardiomyopathy);
- 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;
- Cardiac arrest before randomization or occurrence of 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 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified