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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
120
Treatment administration
Treatment administration
Treatment administration
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
Mortality
Time frame: Day 28, Day 60, Day 90
Number of temporary mechanical circulatory support free days
Time frame: Day 28
Number of inotropes-free days
Time frame: Day 28
Incidence of ventricular assisted device use
Time frame: Day 28, Day 60, Day 90
Incidence of heart transplant
Time frame: Day 28, Day 60, Day 90
Left ventricular function (%) assessed by echocardiography (Simpson method)
Time frame: Day 3, Day 7, Day 14, Day 28
Time to normalize troponin
Time frame: From randomization to Day 14
Time to normalize N-terminal pro-B-type natriuretic peptide
Time frame: From randomization to Day 14
Incidence of drugs side effects
nosocomial infections, significant gastrointestinal bleeding, renal insufficiency, acute delirium leading to the use of neuroleptic agents
Time frame: From randomization to Day 28
Proportion of patients with left ventricular ejection fraction < 55%
Time frame: Day 28, 6 months
Proportion of patients with left ventricular dilatation
Time frame: Day 28, 6 months
Proportion of patients with late gadolinium enhancement evaluated by cardiac magnetic resonance imaging
Time frame: 6 months
Incidence of hyperglycemia
Time frame: From randomization to Day 14
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