Patients with endomyocardial biopsy (EMB) proven inflammatory cardiomyopathy (ICM) defined by EMB established presence of myocardial inflammation and absence of cardiotropic infectious agents established by PCR.
Conditions
Interventions
Trade Name: Prednison 5 léciva
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisonum
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrati
Sponsors
Fakultní nemocnice u sv. Anny v Brne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged 18 to 65 years at the time of signing the informed consent 2. Signing of the informed consent. 3. LV systolic dysfunction defined by ejection fraction less than or equal 40% as assessed by echocardiography and symptoms of heart failure (minimum NYHA class II) lasting for at least 2 weeks at the time of randomization. This criterion also determines the inclusion of the study subjects in one of two substudies (CZECH-ICIT 1 or CZECH-ICIT 2). - LV systolic dysfunction (defined by ejection fraction less than or equal 40%) and symptoms of heart failure (minimun NYHA class II) lasting 2 weeks to 6 months, with standard medical therapy of chronic heart failure given for at least 2 weeks – the subject fullfills criterion for inclusion in CZECH-ICIT 1 substudy - LV systolic dysfunction (defined by ejection fraction less than or equal 40%) and symptoms of heart failure (minimum NYHA class II) lasting more than 6 months, with standard medical therapy of chronic heart failure given for at least 2 weeks – the subject fullfills criterion for inclusion in CZECH-ICIT 2 substudy 4. Positive imunohistochemistry finding of myocardial inflammation in endomycardial biopsy (EMB). EMB must have been be performed no more than 6 weeks prior to the inclusion in the study. Positive imunohistochemistry EMB finding demonstrating myocardial inflammation is defined by the presence of at least 7/mm2 CD-3 positive lymphocytes and/or at least 14 infiltrating leucocytes (LCA+ cells)/mm2 in the specimen. 5. The absence of infectious agent in EMB is defined by negative results of PCR testing of EMB specimens. PCR testing will be aimed to exclude the presence of enteroviruses (ECHO, coxsackie), adenoviruses, herpes viruses (HSV-1, EBV, CMV, HHV-6), Borrelia burgdorferi and parvorvirus B19. In the case of parvovirus B19, a negative PCR result will be considered when less than 500 viral copies/ug genomic DNA are detected. EMB must have been performed no more than 6 weeks prior to the inclusion in the study. 6. Negative blood pregnancy test in fertile females. 7. Effective form of contraception in fertile females (hormonal contraception and/or 2 barrier contraception) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 234 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. The presence of coronary artery disease, defined by angiographic findings of one or more coronary artery stenosis > 50%, history of previous myocardial infarction and/or percutaneous or surgical myocardial revascularization. Coronary angiography must not have been performed more than 2 years before randomization into the study. 2. Permanent pacemaker including cardiac resynchronization therapy. 3. The presence of uncontrolled, persistent supraventricular tachyarrhythmia, with ventricular rate > 120/min, lasting more than 1 week before EMB. 4. The presence of uncontrolled arterial hypertension, defined by blood pressure values > 180mmHg (for systolic) and/or > 110mmHg (for diastolic) lasting more than 3 months. 5. The presence of at least moderately hemodynamically significant primary valvulopathy or congenital heart disease (apart from patent foramen ovale and non-significant atrial septal defect). 6. Previous heart valve surgery (replacement or reconstruction) or surgical correction of congenital heart disease. 7. A history of cytostatic therapy or radiotherapy. 8. Alcoholism defined as ethanol intake >90 g/day. 9. The presence of uncontrolled endocrine of metabolic disorder. 10. Gravidity and lactation. 11. Known hypersensitivity to investigational drugs. 12. All contraindications of immunosuppresive therapy according to SmPC: mainly untreated systemic infection, poorly managable diabetes mellitus, osteoporosis, florid gastric or duodenal ulcer, uncontrolled arterial hypertension, history of malignant disease with oncological treatment finished less than 5 years, proven immunodeficiency, renal of hepatic insufficiency (serum creatinine > 200 µmol/l; ALT and/or AST activity greater than three times the standard), leukocytopenia (leucocytes less than 4 x 109/l), trombocytopenia (platelets less than 100 x 109/l), anemia (hemoglobin concentration less than 100 g/l).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Comparison of the change in LV ejection fraction (evaluated by echocardiography) in patients treated with two different dosing regimens of combined immunosuppresive therapy given on the top standard medical therapy of chronic heart failure and in patients treated only with standard medical therapy of chronic heart failure according to current guidelines.;Secondary Objective: 1. Comparison of the change of LV end-diastolic and end-systolic diameters 2. Comparison of the change in NYHA class 3. Comparison o the occurrence of the combined end-point (death from cardiac reasons, heart transplantation, hospitalization for heart failure, succesfull resuscitation for cardiac arrest and adequate ICD shock for ventricular tachycardia or ventricular fibrillation) 4. Comparison of the total mortality 5. Comparison of the number of infiltrating inflammatory cells in EMB (lymfocytes and LCA+ cells/mm2) 6. Comparison of the overall tolerability and adverse events occurrence ;Primary end point(s): The change in LV ejection fraction ;Timepoint(s) of evaluation of this end point: 12 months after the initiation of immunosuppresive therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The change of LV end-diastolic and end-systolic diameters 2. The change of NYHA class 3. Total mortality 4. Combined end-point (death from cardiac reasons, heart transplantation, hospitalization for heart failure, succesfull resuscitation for cardiac arrest and adequate ICD shock for ventricular tachcardia or ventricular fibrillation) 5. Change of the number of infiltrating inflammatory cells in EMB (lymfocytes and LCA+ cells/mm2) ;Timepoint(s) of evaluation of this end point: 12 months after the initiation of immunosuppresive therapy | — |
Countries
Czech Republic
Contacts
Public ContactOddelení klinických studií
Fakultní nemocnice u sv. Anny v Brne
Outcome results
None listed