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About
Double blind RCT aiming to compare the efficacy of Anakinra vs placebo, on top of the standard of care, on restoration of myocardial function at 3 days following treatment initiation, in children admitted for acute myocarditis in intensive care units.
Full description
Activation of the inflammasome is increasingly recognized in the pathogenesis of acute myocarditis. We hypothesize that by blocking inflammasome using anakinra, we interfere with the key mechanism driving myocardial inflammation and fibrosis, allowing for restauration of myocardial function compared to standard of care alone. Children from ≥ 3 months to < 18 years of age hospitalized in the Intensive Care Unit for acute myocarditis defined as a reduced left ventricle ejection fraction below 50% and troponin T rise (>1.5x normal range) will be randomized to either receive SC Anakinra or Placebo in addition to standard of care treatment. Primary endpoint: Proportion of children with recovered left ventricle ejection fraction (LVEF ≥ 50%) measured by echocardiography at 3 days after treatment initiation.
Secondary endpoints:
Proportion of children with recovered left ventricle ejection fraction (LVEF
≥ 50%) measured by echocardiography at 7 and 28 days after treatment initiation. Patients who die or undergo heart transplant within the first 7 and 28 days after treatment initiation respectively will be considered as a failure (i.e, LVEF < 50%). Patients who still require ECMO at 7 and 28 days after treatment initiation respectively will also be considered as failure (i.e., LVEF < 50%).
Time to recovery of normal left ventricular ejection fraction (LVEF ≥ 50%) within the first 3 days after treatment initiation
Proportion of children requiring ECMO within the first 3 days after treatment initiation
Proportion of children who undergo heart transplant within 6 months after treatment initiation
Time to all-cause death within 6 months after treatment initiation
Time to cardiovascular-related death within 6 months after treatment initiation
Proportion of children with drug-related side effects (hypersensitivity, neutropenia, drug-related liver enzymes elevation…)
a- NT proBNP at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation - Troponin T at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation - Proportion of children with ventricular tachycardia assessed by EKG at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation - b - NT proBNP at 7 days following treatment initiation - Troponin T at 7 days following treatment initiation - Proportion of children with ventricular tachycardia assessed by EKG at 7 days following treatment initiation - Proportion of children with fibrosis on cardiac MRI according to modified Lake Louise criteria at 6 months following treatment initiation - Proportion of children with dilated cardiomyopathy on cardiac echocardiography (Left ventricular end diastolic diameter ˃ 2 SD with altered systolic function <50%) at 3 and 6 months following treatment initiation - Proportion of children with ventricular arrhythmia at 6 months following treatment initiation.
Enrollment
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Inclusion criteria
Exclusion criteria
Children weighing less than 5 Kgs
Known anterior cardiomyopathy or operated cardiopathy
Neutropenia (< 1,5 × 10^9 /L).
Known hypersensitivity to Anakinra or any of its excipients (citric acid anhydrous, sodium chloride, disodium EDTA dihydrate, polysorbate 80, E. coli derived proteins)
Administration of a live vaccine in the 4 weeks prior to inclusion
Hepatitis B infection, defined as positive HBsAg and/or detectable HBV DNA (PCR). Patients with increased risk of Tuberculosis (TB) infection
Recent tuberculosis infection or with active TB
Patients with overt concomitant bacterial infection
Patients previously treated with another biotherapy
Patients with any type of immunodeficiency or cancer
Anti TNF-α within the past 14 days
Malignancy or history of malignancy or any comorbidity limiting survival or conditions predicting inability to complete the study Ongoing or recent use of any other medication Known inhibitors/inducers of cytochrome P450
Pregnancy or breastfeeding
No affiliation to the Social Security
Current enrollment in another clinical trial
Inability of the legal representative (and the patient, when applicable) to understand the national language (French)
Primary purpose
Allocation
Interventional model
Masking
110 participants in 2 patient groups, including a placebo group
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Central trial contact
Ramy CHARBEL, Study Principal Investigator
Data sourced from clinicaltrials.gov
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