CZECH-ICIT (CZECH Inflammatory Cardiomyopathy Immunosuppression Trial)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by St. Anne's University Hospital Brno, Czech Republic
Sponsor:
Information provided by (Responsible Party):
Jan Krejci, MD, Ph.D, St. Anne's University Hospital Brno, Czech Republic
ClinicalTrials.gov Identifier:
NCT01877746
First received: June 28, 2012
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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).


Condition Intervention Phase
Inflammatory Cardiomyopathy
Drug: Combination of prednisone and azathioprine
Other: No intervention
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by St. Anne's University Hospital Brno, Czech Republic:

Primary Outcome Measures:
  • comparison of the change in LV ejection fraction [ Time Frame: baseline and in 12 months after the initiation of immunosuppressive therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • comparison of the change of LV end-diastolic and end-systolic diameters [ Time Frame: baseline and in 12 months after the initiation of immunosuppressive therapy ] [ Designated as safety issue: No ]
  • comparison of the change of New York Heart Association (NYHA) class [ Time Frame: baseline and in 12 months after the initiation of immunosuppressive therapy ] [ Designated as safety issue: No ]
  • comparison of total mortality [ Time Frame: baseline and in 12 months after the initiation of immunosuppressive therapy ] [ Designated as safety issue: No ]
  • comparison of the combined end-point [ Time Frame: baseline and in 12 months after the initiation of immunosuppressive therapy ] [ Designated as safety issue: No ]
    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

  • comparison of the change in the number of infiltrating inflammatory cells in EMB [ Time Frame: baseline and in 12 months after the initiation of immunosuppressive therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 234
Study Start Date: January 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R1 - combined immunosuppressive therapy
application of the combined immunosuppressive therapy in the first dosing regimen
Drug: Combination of prednisone and azathioprine
  • Prednisone for a total of 90 days, with initial dose 1mg/kg/day p.o., given for 12 days and then tapered every 5 days for 5mg/day to the maintenance dose of 0.2mg/kg/day. The daily dose of Prednisone will be rounded to the nearest value divisible by 5.
  • Azathioprine for 100 days in total, with dose 1 mg/kg/day. The daily dose of Azathioprine will be rounded to the nearest value divisible by 25.
Experimental: R2 - combined immunosuppressive therapy
application of the combined immunosuppressive therapy in the second dosing regimen
Drug: Combination of prednisone and azathioprine
  • Prednisone for a total of 6 months, with initial dose 1mg/kg/day p.o. given for 4 weeks with a subsequent maintenance dose of 0,33 mg/kg/den. The daily dose of Prednisone will be rounded to the nearest value divisible by 5.
  • Azathioprine for 6 months in total, with dose 2mg/kg/day. The daily dose of Azathioprine will be rounded to the nearest value divisible by 25.
S - standard therapy
only standard medical therapy of chronic heart failure without application of the combined immunosuppressive therapy
Other: No intervention
No intervention, only standard medical therapy

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (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
  4. 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.
  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 (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.
  6. Negative blood pregnancy test in fertile females.
  7. Usage of the effective method of contraception (hormonal or 2 barrier method of contraception)

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 pressure) and/or 110mmHg (for diastolic pressure) 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. adu.
  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 immunosuppressive therapy according to Summary of product characteristics (SmPC) of both investigational medicinal products: untreated systemic infection, poorly manageable 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; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) activity greater than three times the standard), leukocytopenia (leucocytes less than 4 x 10 9/l), thrombocytopenia (platelets less than 100 x 10 9/l), anemia (hemoglobin concentration less than 100 g/l).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01877746

Locations
Czech Republic
St. Anne`s University Hospital Brno Recruiting
Brno, Czech Republic
Contact: Jan Krejci, MD, Ph.D    543 182 405 ext 00420    jan.krejci@fnusa.cz   
Principal Investigator: Jan Krejci, MD, Ph.D         
General University hospital in Prague Recruiting
Prague, Czech Republic
Contact: Tomas Palecek, Assoc. professor    224 962 634 ext 00420    tpalec@lf1.cuni.cz   
Principal Investigator: Tomas Palecek, Assoc. prof.         
Sponsors and Collaborators
St. Anne's University Hospital Brno, Czech Republic
Investigators
Principal Investigator: Jan Krejci, MD, Ph.D employee
Principal Investigator: Tomas Palecek, Assoc. prof. without affiliation
  More Information

Publications:
Responsible Party: Jan Krejci, MD, Ph.D, MD, Ph.D, St. Anne's University Hospital Brno, Czech Republic
ClinicalTrials.gov Identifier: NCT01877746     History of Changes
Other Study ID Numbers: ICRC-ICIT-01
Study First Received: June 28, 2012
Last Updated: June 11, 2013
Health Authority: Czech Republic: State Institute for Drug Control

Keywords provided by St. Anne's University Hospital Brno, Czech Republic:
ICM
myocarditis
cardiomyopathy
endomyocardial biopsy
immunosuppression

Additional relevant MeSH terms:
Cardiomyopathies
Cardiovascular Diseases
Heart Diseases
Azathioprine
Immunosuppressive Agents
Prednisone
Anti-Inflammatory Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014