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The aim of this study is to compare the effect of combined immunosuppressive therapy given on the top standard medical therapy of chronic heart failure according to current guidelines with standard medical therapy of chronic heart failure alone in patients with infammatory cardiomyopathy (ICM).
Suitable subjects are characterized by EMB established presence of myocardial inflammation / negative polymerase chain reaction assay (PCR) findings of cardiotropic infectious agents and with varying duration of heart failure symptoms and left ventricular (LV) systolic dysfunction (phase A).
Further, to compare the effect of two regimens of combined immunosuppressive therapy in these patients with ICM (phase B).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| R1 - combined immunosuppressive therapy | Experimental | application of the combined immunosuppressive therapy in the first dosing regimen |
|
| R2 - combined immunosuppressive therapy | Experimental | application of the combined immunosuppressive therapy in the second dosing regimen |
|
| S - standard therapy | Other | only standard medical therapy of chronic heart failure without application of the combined immunosuppressive therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combination of prednisone and azathioprine | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| comparison of the change in LV ejection fraction | baseline and in 12 months after the initiation of immunosuppressive therapy |
| Measure | Description | Time Frame |
|---|---|---|
| comparison of the change of LV end-diastolic and end-systolic diameters | baseline and in 12 months after the initiation of immunosuppressive therapy | |
| comparison of the change of New York Heart Association (NYHA) class | baseline and in 12 months after the initiation of immunosuppressive therapy |
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Inclusion Criteria:
Males and females aged 18 to 65 years at the time of signing the informed consent
Signing of the informed consent.
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).
Positive immunohistochemistry finding of myocardial inflammation in endomyocardial biopsy (EMB). EMB must have been be performed no more than 6 weeks prior to the inclusion in the study. Positive immunohistochemistry EMB finding demonstrating myocardial inflammation is defined by the presence of at least 7/mm2 cluster of differentiation 3 (CD3) positive lymphocytes and/or at least 14 infiltrating leucocytes (LCA+ cells)/mm2 in the specimen.
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 (herpes simplex virus (HSV-1), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus (HHV-6)), Borrelia burgdorferi and parvovirus 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.
Negative blood pregnancy test in fertile females.
Usage of the effective method of contraception (hormonal or 2 barrier method of contraception)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jan Krejci, MD, Ph.D | employee | Principal Investigator |
| Tomas Palecek, Assoc. prof. | without affiliation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Anne's University Hospital Brno | Recruiting | Brno | Czechia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11435335 | Background | Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, Glanowska G, Wilczewski P, Niklewski T, Zembala M, Polonski L, Rozek MM, Wodniecki J. Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results. Circulation. 2001 Jul 3;104(1):39-45. doi: 10.1161/01.cir.104.1.39. | |
| 19556262 |
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| ID | Term |
|---|---|
| D009205 | Myocarditis |
| D009202 | Cardiomyopathies |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D001379 | Azathioprine |
| ID | Term |
|---|---|
| D013872 | Thionucleosides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D015122 | Mercaptopurine |
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|
| Combination of prednisone and azathioprine | Drug |
|
|
| No intervention | Other | No intervention, only standard medical therapy |
|
| comparison of total mortality | baseline and in 12 months after the initiation of immunosuppressive therapy |
| comparison of the combined end-point | combined end-point (death from cardiac reasons, heart transplantation, hospitalization for heart failure, successful resuscitation for cardiac arrest and adequate implantable cardioverter-defibrillator (ICD) shock for ventricular tachycardia or fibrillation | baseline and in 12 months after the initiation of immunosuppressive therapy |
| comparison of the change in the number of infiltrating inflammatory cells in EMB | baseline and in 12 months after the initiation of immunosuppressive therapy |
| General University hospital in Prague | Recruiting | Prague | Czechia |
|
| Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. Eur Heart J. 2009 Aug;30(16):1995-2002. doi: 10.1093/eurheartj/ehp249. Epub 2009 Jun 25. |
| D011687 |
| Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |