Pulse Corticosteroids Or/and Immunoglobulins to Treat Fulminant Myocarditis

NCT ID: NCT06896253

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-30
• Study Completion Date: 2029-11-30

Brief Summary

Fulminant myocarditis (FM) is the most severe manifestation of acute myocarditis, an acute inflammatory myocardial disease most often triggered by viral infections.

Currently, the most accepted definition of FM requires acute illness, hemodynamic compromise due to cardiogenic shock, and need for hemodynamic support (inotropes and/or temporary mechanical circulatory support (t-MCS) in the absence of an ischemic cause or other pre-existing cardiomyopathies. Unfortunately, there is a paucity of evidence-based management strategies for this disease and the management of patients affected by FM often varies according to local experience and practice with the role of immunosuppression being the most debated issue.

Besides, due to inconsistent results obtained in several studies and frequent spontaneous recovery with supportive therapy alone, immunosuppression is largely debated in the setting of lymphocytic myocarditis (LM). Among available medications for this disease, corticosteroids are often used despite a lack of clear evidence in the context of FM. Similarly, intravenous immunoglobulin (IVIG) has both antiviral and anti-inflammatory effects on myocarditis. In adults, a recent meta-analysis based on case series showed that IVIG therapy significantly reduced in-hospital mortality, improved the left ventricular ejection fraction, and significantly increased the survival rate in patients with FM. More recently, FM among patients with COVID-19, including post-infectious multisystem inflammatory syndrome, has been reported in young adult patients. These severe forms have been successfully treated with intravenous corticosteroids and IVIG, highlighting the relevance of the systemic inflammatory response in determining cardiac injury in COVID-19, even though more evidence is needed.

Conditions

Myocarditis Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Pulse bolus corticosteroids group

1. 1 gram/day of methylprednisolone IV for three days followed by 1mg/kg/day IV until inotropes weaning or 7 days whatever come first.

2. Placebo of IVIG: glucose 5% 0.5g/kg/day for 4 days

Group Type: EXPERIMENTAL

Pulse bolus corticosteroids

Intervention Type: DRUG

Treatment administration

Pulse bolus corticosteroids and IVIG group

1. 1 gram/day of methylprednisolone IV for three days followed by 1mg/kg/day IV until inotropes weaning or 7 days whatever come first.

2. 0.5g/kg/day IVIG for 4 days.

Group Type: EXPERIMENTAL

Pulse bolus corticosteroids and IVIG

Intervention Type: DRUG

Treatment administration

Double placebo pulse bolus corticosteroids (G5%) and IVIG (G5 %)

Group Type: PLACEBO_COMPARATOR

Pulse bolus corticosteroids (G5%) and IVIG (G5 %)

Intervention Type: DRUG

Treatment administration

Interventions

Pulse bolus corticosteroids

Treatment administration

Intervention Type: DRUG

Pulse bolus corticosteroids and IVIG

Treatment administration

Intervention Type: DRUG

Pulse bolus corticosteroids (G5%) and IVIG (G5 %)

Treatment administration

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Fulminant myocarditis defined by

• the acute illness (<1 month from symptom onset),
• hemodynamic compromise due to cardiogenic shock (confirmed by echocardiography) or electrical storm,
• elevated plasma cardiac troponin > twice normal value
• need for hemodynamic support (inotropes or temporary mechanical circulatory support) for less than 72 hours in the absence of an ischemic cause or other pre-existing cardiomyopathies Noticeably, a coronary angiogram should be performed in patients ≥40 years of age when myocarditis has not been proven histologically. Besides, an endomyocardial biopsy will not be mandatory to fulfill the definition of fulminant myocarditis.

2. Signed informed consent from the patient, a close relative or surrogate or a family member or a legal representative for minor patient.

• Adult : According to the specifications of emergency inclusion, randomization without the close relative/surrogate consent could be performed if the patientis unable to give his/her consent and when the close relative/surrogate/family member are absent. Close relative/surrogate/family member consent will be asked as soon as possible after randomization. The patient will be asked as soon as possible to give his/her consent for the continuation of the trial when his/her condition will allow.
• Minor : According to the specifications of emergency inclusion, randomization could be performed when legal representative are absent. Legal representative consent will be asked as soon as possible after randomization 3. Social security registration (AME excluded)

Exclusion Criteria

• 1. Age <15 2. Pregnancy or breastfeeding or baby delivery <6 months 3. Initiation of inotropes or temporary mechanical circulatory support >72 hours 4. Resuscitation >20 minutes (cumulative low-flow time > 20 minutes ) 5. Pre-existing ischemic or dilated cardiomyopathy or Tako-Tsubo evaluated by echocardiography.

6. Known systemic autoimmune disorder or other conditions requiring immunosuppression 7. Patients with peripheral eosinophilia (≥1000 G/L) 8. Myocarditis associated with anti-cancer immune checkpoint inhibitor agents 9. Active severe bacterial or fungal infectious disease 10. Patient moribund on the day of randomization, SAPS II >90 11. Contraindication or allergies to corticosteroids or immunoglobulins or any components of the formulations or their excipients 12. Patients already on corticosteroids or receiving IVIG 13. Participation in another interventional study or being in the exclusion period at the end of a previous study.

14. Patients with an uncontrolled psychotic condition Patients with known anti-IgA antibodies in line with the contraindications of methylprednisolone IV and of IVIg based products respectively

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alain COMBES, MD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Central Contacts

Matthieu SCHMIDT, MD

Role: CONTACT

matthieu.schmidt@aphp.fr

33142162937

Other Identifiers

2023-506599-28-01

Identifier Type: CTIS

Identifier Source: secondary_id

APHP220808

Identifier Type: -

Identifier Source: org_study_id