Clinical Trials/NCT01877746

NCT01877746

Unknown

Phase 3

RANDOMIZED, MULTICENTRIC STUDY COMPARING THE EFFECT OF TWO REGIMENS OF COMBINED IMMUNOSUPPRESSIVE THERAPY IN THE TREATMENT OF INFLAMMATORY CARDIOMYOPATHY CZECH-ICIT (CZECH INFLAMMATORY CARDIOMYOPATHY IMMUNOSUPPRESSION TRIAL)

St. Anne's University Hospital Brno, Czech Republic2 sites in 1 country234 target enrollmentJanuary 2013

ConditionsInflammatory Cardiomyopathy

InterventionsCombination of prednisone and azathioprine No intervention

DrugsCombination of prednisone and azathioprine

Overview

Phase: Phase 3
Intervention: Combination of prednisone and azathioprine
Conditions: Inflammatory Cardiomyopathy
Sponsor: St. Anne's University Hospital Brno, Czech Republic
Enrollment: 234
Locations: 2
Primary Endpoint: comparison of the change in LV ejection fraction
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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).

Registry

clinicaltrials.gov

Start Date

January 2013

End Date

September 2015

Last Updated

12 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

St. Anne's University Hospital Brno, Czech Republic

Responsible Party

Principal Investigator

Jan Krejci, MD, Ph.D

MD, Ph.D

St. Anne's University Hospital Brno, Czech Republic

Eligibility Criteria

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).
•LV systolic dysfunction (defined by ejection fraction less than/or equal 40%) and symptoms of heart failure (minimum 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 fulfills 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 fulfills criterion for inclusion in CZECH-ICIT 2 substudy
•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 B
•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

•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.
•Permanent pacemaker including cardiac resynchronization therapy.
•The presence of uncontrolled, persistent supraventricular tachyarrhythmia, with ventricular rate \> 120/min, lasting more than 1 week before EMB.
•The presence of uncontrolled arterial hypertension, defined by blood pressure values \> 180mmHg (for systolic pressure) and/or 110mmHg (for diastolic pressure) lasting more than 3 months.
•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).
•Previous heart valve surgery (replacement or reconstruction) or surgical correction of congenital heart disease. adu.
•A history of cytostatic therapy or radiotherapy.
•Alcoholism defined as ethanol intake \>90 g/day.
•The presence of uncontrolled endocrine of metabolic disorder.
•Gravidity and lactation.

Arms & Interventions

R1 - combined immunosuppressive therapy

application of the combined immunosuppressive therapy in the first dosing regimen

Intervention: Combination of prednisone and azathioprine

R2 - combined immunosuppressive therapy

application of the combined immunosuppressive therapy in the second dosing regimen

Intervention: Combination of prednisone and azathioprine

S - standard therapy

only standard medical therapy of chronic heart failure without application of the combined immunosuppressive therapy

Intervention: No intervention

Outcomes

Primary Outcomes

comparison of the change in LV ejection fraction

Time Frame: baseline and in 12 months after the initiation of immunosuppressive therapy

Secondary Outcomes

comparison of total mortality(baseline and in 12 months after the initiation of immunosuppressive therapy)
comparison of the combined end-point(baseline and in 12 months after the initiation of immunosuppressive therapy)
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)
comparison of the change in the number of infiltrating inflammatory cells in EMB(baseline and in 12 months after the initiation of immunosuppressive therapy)