Pulse Corticosteroids Or/and Immunoglobulins to Treat Fulminant Myocarditis

NCT06896253 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: APHP2208082023-506599-28-01
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

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

Keywords

Fulminant myocarditis

Outcome Measures

Primary Outcomes (1)

• A composite hierarchical outcome composed of four components : 1) mortality at D28 2) heart transplant/VAD/persisting t-MCS at D28, and 3) number of days alive without t-MCS and inotropes at D28

  Each patient will be compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better. If one patient survived without heart transplantation or long-term assist ventricular device or t-MCS still ongoing at day 28 and the other does not, scores of +1 and -1 will be assigned, respectively. Otherwise, the assigned score will depend on which patient had more days free from t-MCS and inotropes: the patient with more days off t-MCS and inotropes will receive a score of +1, and the other patient -1. If both patients survived and had the same number of days off t-MCS and inotropes, or if both patients died or had a heart transplant or a VAD, they will be both assigned a score of 0 for that pairwise comparison. For each patient, scores for all pairwise comparisons will be summed, resulting in a cumulative score which will be the primary endpoint of the study.

  Day 28

Secondary Outcomes (13)

• Mortality

  Day 28, Day 60, Day 90

• Number of temporary mechanical circulatory support free days

  Day 28

• Number of inotropes-free days

  Day 28

• Incidence of ventricular assisted device use

  Day 28, Day 60, Day 90

• Incidence of heart transplant

  Day 28, Day 60, Day 90

Study Arms (3)

Pulse bolus corticosteroids group

EXPERIMENTAL

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

Drug: Pulse bolus corticosteroids

Pulse bolus corticosteroids and IVIG group

EXPERIMENTAL

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.

Drug: Pulse bolus corticosteroids and IVIG

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

PLACEBO COMPARATOR

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

Interventions

Pulse bolus corticosteroids DRUG

Treatment administration

Pulse bolus corticosteroids group

Pulse bolus corticosteroids and IVIG DRUG

Treatment administration

Pulse bolus corticosteroids and IVIG group

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

Treatment administration

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

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• \. 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.
• \. 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Interventions

Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Alain COMBES, MD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Central Study Contacts

Matthieu SCHMIDT, MD

CONTACT

33142162937; matthieu.schmidt@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Sponsor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2025
• First Posted: March 26, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: March 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal