Endomyocardial biopsy proven virus-negative myocarditis with left ventricular ejection fraction lower than 55%. MedDRA version: 20.1 Level: PT Classification code 10064539 Term: Autoimmune myocarditis System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: KINERET 100 mg/0,67 ml soluzione iniettabile uso sc siringhe preriempite
Product Name: KINERET
Product Code: [035607062]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AN
Sponsors
OSPEDALE SAN RAFFAELE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 18 Years to 75 Years. Myocarditis defined on endomyocardial biopsy according to Dallas criteria and to immunohistochemical criteria (CD3+ >7/mm2). Any impairment of left ventricular ejection fraction (LV-EF) =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: Coronary artery stenosis > 50% at angiography or coronary CT Scan (acceptable if performed during the last 12 months). Evidence of genome of cardiotropic viruses by Polymerase chain reaction on EBM. Clinical suspicion or proven underlying disease: Lyme disease, any other bacterial disease possibly responsible for myocarditis, trypanosomiase disease, giant cell myocarditis. Known presence or suspicion of active or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Pregnancy, breastfeeding. Female patients of childbearing potential may participate if adequate contraception is used during the study. (For the purposes of this trial, women of childbearing potential are defined as “All female subjects after puberty unless they are post-menopausal for at least 2 years or are surgically sterile.”). Contra-indication to ANAKINRA (known hypersensitivity to the active substance or to any of the excipients or to Escherichia coli-derived proteins). Presence of neutropenia 10 mg daily and/or immuno-suppressive agents within 3 months before the enrolment. Hepatic impairment = Child-Pugh Class C. Mechanical ventilation circulatory assistance. Congenital and/or acquired valvular disease or any other heart disease that could justify the severity of cardiac dysfunction. Major surgery within 2 weeks prior to randomization, or unhealed operation wounds.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Anakinra in addition to standard immunosuppressive therapy at improving Left Ventricular Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE) at 2 months.;Secondary Objective: To evaluate the efficacy of Anakinra in reducing venricular arrhythmias on 24h-ECG Holter at 3 different time points: 2 weeks, 2 months and 6 months. To evaluate the efficacy of Anakinra in improving Left Ventricular Ejection Fraction(LVEF) at 2 weeks and at 6 months and to imprrove LV volumes and diameters at 3 different time points(2 weeks, 2 months and 6 months). To evaluate the efficacy of Anakinra in preventing myocarditis complications (ventricular arrhythmias, heart failure, chest pain, syncope) and decreasing Cardiovascular deaths rate at 2 weeks, 2 months and 6 months. To assess the ability of Anakinra in improving patient's symptoms (New York Heart Association dyspnea class), quality of life ( patients reported outcomes), cardiac enzymes and inflammatory markers at 2 weeks, 2 months and 6 months. To evaluate the safety of anakinra in the treatment of myocarditis at 4 different time points: baseline, 2 weeks, 2 months and at 6 months.;Primary end point(s): 2-months improvement in left-ventricular function, based on the increase of left ventricular (LV) ejection fraction (EF) assessed by transthoracic echocardiography.;Timepoint(s) of evaluation of this end point: 2 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Arrhytmic burden (number of ventricular and supraventricular ectopic beats, runs of sutained or non-sustained ventricular tachycardia) at 3 different time points: 2 weeks, 2 months and 6 months.; LVEF assessed by TTE at 2 weeks and at 6 months; LV volumes and diameters on TTE at 3 different time points: 2 weeks, 2 months and 6 months.; Heart failure symptoms [NYHA class], PROs (Minnesota Living with SF36, Heart Failure and Kansas City Cardiomiopathy questionnaires), QALYs and 6-minute walking test at 3 different time points: 2 weeks, 2 months and 6 months.; Inflammatory markers (CRP, ESR, IL1RA, IL1¿, IL1¿, IL6 and IL18) serum levels at 3 different time points: 2 weeks, 2 months and 6 months.; Number of days alive free of any myocarditis complications defined as ventricular arrhythmias, heart failure, chest pain, syncope, at 3 different time points: 2 weeks, 2 months and 6 months.; Reduction in all cause of death, cardiovascular death and heart failure rate at 3 different time points: 2 weeks, 2 months and 6 months.; 2 settimane, 2 mesi e 6 mesi; Cardiac biomarkers (NT-proBNP and high sensitive troponin T) serum levels at 2 weeks, 2 months and 6 months.;Timepoint(s) of evaluation of this end point: 2 weeks, 2 months and 6 months; 2 weeks and at 6 months; 2 weeks, 2 months and 6 months; 2 weeks, 2 months and 6 months; 2 weeks, 2 months and 6 months.; 2 weeks, 2 months and 6 months; 2 weeks, 2 months and 6 months; Baseline, 2 weeks, 2 months and 6 months; 2 weeks, 2 months and 6 months | — |
Countries
Italy
Contacts
Public ContactUnità di Immunologia, Reumatologia,
IRCCS San Raffaele
Outcome results
None listed