Pulse Corticosteroids Or/and Immunoglobulins to Treat Fulminant Myocarditis

Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age15+
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Pulse bolus corticosteroids

    Drug

    Treatment administration

  • Pulse bolus corticosteroids and IVIG

    Drug

    Treatment administration

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

    Drug

    Treatment administration

Treatment groups

120 Participants
are divided into 3 treatment groups
Group A: Pulse bolus corticosteroids groupExperimental treatment 1 intervention
Group B: Pulse bolus corticosteroids and IVIG groupExperimental treatment 1 intervention
Group C: Double placebo pulse bolus corticosteroids (G5%) and IVIG (G5 %)Placebo comparator 1 intervention

Trial outcomes

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.

Time frame
Day 28

Secondary outcomes

1

Mortality

Time frame
Day 28, Day 60, Day 90
2

Number of temporary mechanical circulatory support free days

Time frame
Day 28
3

Number of inotropes-free days

Time frame
Day 28
4

Incidence of ventricular assisted device use

Time frame
Day 28, Day 60, Day 90

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

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