CZECH-ICIT (CZECH Inflammatory Cardiomyopathy Immunosuppression Trial)

NCT01877746 | Unknown Phase 3

• 1 other identifier: ICRC-ICIT-01
• Study Type: interventional
• Target: 234
• Locations: 1 country
• Sites: 2

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).

Conditions

Inflammatory Cardiomyopathy

Keywords

ICM; myocarditis; cardiomyopathy; endomyocardial biopsy; immunosuppression

Outcome Measures

Primary Outcomes (1)

• comparison of the change in LV ejection fraction

  baseline and in 12 months after the initiation of immunosuppressive therapy

Secondary Outcomes (5)

• 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 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 in the number of infiltrating inflammatory cells in EMB

  baseline and in 12 months after the initiation of immunosuppressive therapy

Study Arms (3)

R1 - combined immunosuppressive therapy

EXPERIMENTAL

application of the combined immunosuppressive therapy in the first dosing regimen

Drug: Combination of prednisone and azathioprine

R2 - combined immunosuppressive therapy

EXPERIMENTAL

application of the combined immunosuppressive therapy in the second dosing regimen

Drug: Combination of prednisone and azathioprine

S - standard therapy

OTHER

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

Other: No intervention

Interventions

Combination of prednisone and azathioprine DRUG

* 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.

R1 - combined immunosuppressive therapy

No intervention OTHER

No intervention, only standard medical therapy

S - standard therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females aged 18 to 65 years at the time of signing the informed consent
• Signing of the informed consent.
• Negative blood pregnancy test in fertile females.
• Usage of the effective method of contraception (hormonal or 2 barrier method of contraception)

You may not qualify if:

• 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.
• Known hypersensitivity to investigational drugs.
• 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).

Sponsors & Collaborators

• St. Anne's University Hospital Brno, Czech Republic: lead

Study Sites (2)

St. Anne's University Hospital Brno

Brno, Czechia

RECRUITING

General University hospital in Prague

Prague, Czechia

RECRUITING

Related Publications (2)

• 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.

  PMID: 11435335 BACKGROUND

• 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.

  PMID: 19556262 BACKGROUND

MeSH Terms

Conditions

Myocarditis; Cardiomyopathies

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jan Krejci, MD, Ph.D

  employee

  PRINCIPAL INVESTIGATOR

• Tomas Palecek, Assoc. prof.

  without affiliation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Ph.D

Study Record Dates

• First Submitted: June 28, 2012
• First Posted: June 14, 2013
• Study Start: January 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: June 14, 2013

Record last verified: 2013-06

Locations

CZ (2)