Myocarditis, inflammatory cardiomyopathy MedDRA version: 20.0 Level: PT Classification code 10028606 Term: Myocarditis System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Azathioprine VIS, 50mg, tablets
Product Name: Azathioprine 50 mg, tablets
Product Code: not applicable
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coat
Sponsors
Medical University of Warsaw
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for inclusion in this study, patient must fulfill all of the following inclusion criteria: 1. Written informed consent to participate in the IMPROVE-MC study (including two EMBs and two cardiac CMRs) prior to any evaluation or procedure related to the study. 2. Patient with clinically suspected myocarditis or inflammatory cardiomyopathy (according to the criteria of the ESC Working Group on Myocardial & Pericardial Diseases, and ESC Heart Failure Guidelines 2021); OR / AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy who will undergo diagnostic right ventricular (or/and left ventricular) endomyocardial biopsy during the screening OR / AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy confirmed by right ventricular (or/and left ventricular) endomyocardial biopsy that was performed according to the IMPROVE-MC study protocol within 3 months from screening. 3. Men or women aged 18-65. Women of childbearing age must have a negative pregnancy test result. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: Patients fulfilling any of the following exclusion criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients. 1. Presence of contraindications to immunosuppressive therapy with steroids and/ or azathioprine (including hypersensitivity to azathioprine/ 6-mercaptopurine or prednisone, mainly untreated systemic infection, uncontrolled diabetes, poorly controlled endocrine diseases, osteoporosis, active gastric or duodenal ulcer, uncontrolled hypertension, leukocytopenia (leukocyte counts 40 kg/m2 or body weight 1.5 mg/dL. 12. Impaired renal function, defined as eGFR 30%) which could influence the result of LVEF measurement in the investigator’s opinion. 16. Gastrointestinal surgery or gastrointestinal disorder that could interfere with trial drug(s) absorption in the investigator’s opinion. 17. History or presence of any other disease with a life expectancy <3 years. 18. Any contraindications or intolerance to CMR*, including but not limited to: a) the presence of cardiac implantable electronic device implanted <6 weeks ago; b) pacing capture threshold out of the normal range; c) additional cardiac leads (particularly abandoned pacemaker leads), epicardial leads, fractured leads, additional components such as lead
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this trial is to assess the efficacy and safety of 12 – month treatment with prednisone and azathioprine comparing to placebo on top of guideline-recommended medical therapy in patients with biopsy-proven virus negative myocarditis or inflammatory cardiomyopathy and reduced ejection fraction (LVEF 10 - 45%). The study will also assess persistence of the treatment effects after 12 months.;Secondary Objective: Not applicable.;Primary end point(s): LVEF at 12 – months.;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): KEY SECONDARY ENDPOINTS: • Proportion of patients who responded to immunosuppressive therapy as defined by an LVEF increase of = 10% over time. • LVEF at 12 months in subgroups of patients with baseline LVEF = 30% and > 30% • Change in the LV end-systolic and end-diastolic dimensions as well as the LV end-systolic and end-diastolic volumes over time. • Change from baseline in NYHA class over time. • Occurrence of adjudicated heart failure decompensation (hospitalization or ambulatory visit). Secondary endpoints for follow up (compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months): • LVEF at 24 months (maintenance or further improvement). • LVEF at 24 months (maintenance or further improvement) in subgroups of patients with baseline LVEF =30% and >30% • Change in the LV end-systolic and end-diastolic dimensions as well as the LV end-systolic and end-diastolic volumes over time. • Change in NYHA class over time. • Occurrence of adjudicated heart failure decompensation (hospitalization or ambulatory visit). ;Timepoint(s) of evaluation of this end point: Key secondary endpoints will be assessed in 3-month intervals up to 24-months from the randomization. | — |
Countries
Poland
Contacts
Public ContactKrzysztof Ozieranski - PM
1st Chair and Department of Cardiology, University Clinical Center of WUM, Central Clinical Hospital
Outcome results
None listed