Inflammatory CardiomyopathyPhase 3NCT01877746
CZECH-ICIT (CZECH Inflammatory Cardiomyopathy Immunosuppression Trial)
A Phase 3 study testing Combination of prednisone and azathioprine in people with Inflammatory Cardiomyopathy, run by St. Anne's University Hospital Brno, Czech Republic at 2 sites in Czechia.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Inflammatory Cardiomyopathy
- What is being tested?
- Combination of prednisone and azathioprine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 234 participants
- Where
- 2 sitesCzechia
- Study dates
- Jan 2013to Sep 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
Who cannot join
- 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.
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- 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).
Trial locations and contacts
2 sites in 1 country.
Czechia2 sites, 2 recruiting
- Recruiting
St. Anne's University Hospital Brno
Brno
Jan Krejci, MD, Ph.D, 543 182 405 ext. 00420, jan.krejci@fnusa.cz
Jan Krejci, MD, Ph.D
- Recruiting
General University hospital in Prague
Prague
Tomas Palecek, Assoc. professor, 224 962 634 ext. 00420, tpalec@lf1.cuni.cz
Tomas Palecek, Assoc. prof.
About this study
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)
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
- Being tested
- Combination of prednisone and azathioprine, No intervention
- Keywords
- ICM, myocarditis, cardiomyopathy, endomyocardial biopsy, immunosuppression
- Medical subject headings
- Myocarditis, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination of prednisone and azathioprineDrug
- 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.
Combination of prednisone and azathioprineDrug
- 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.
No interventionOther
No intervention, only standard medical therapy
| Study group | Role | What they receive |
|---|---|---|
| R1 - combined immunosuppressive therapy | Experimental | application of the combined immunosuppressive therapy in the first dosing regimen Receives: Drug: Combination of prednisone and azathioprine |
| R2 - combined immunosuppressive therapy | Experimental | application of the combined immunosuppressive therapy in the second dosing regimen Receives: 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 Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
comparison of the change in LV ejection fraction
Measured: 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
Measured: baseline and in 12 months after the initiation of immunosuppressive therapy
comparison of the change of New York Heart Association (NYHA) class
Measured: baseline and in 12 months after the initiation of immunosuppressive therapy
comparison of total mortality
Measured: 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
Measured: baseline and in 12 months after the initiation of immunosuppressive therapy
comparison of the change in the number of infiltrating inflammatory cells in EMB
Measured: baseline and in 12 months after the initiation of immunosuppressive therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2013 (estimated)
- Study startJan 2013
- Primary completionSep 2015 (estimated)
- Study completionSep 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Inflammatory CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 234 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Anne's University Hospital Brno, Czech Republic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jan Krejci, MD, Ph.D, St. Anne's University Hospital Brno, Czech Republic
- Investigators
- Jan Krejci, MD, Ph.D, Principal investigator, employeeTomas Palecek, Assoc. prof., Principal investigator, without affiliation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01877746
- Sponsor's protocol ID
- ICRC-ICIT-01
- Status last verified
- Jun 2013
- First submitted
- 28 Jun 2012
- Last updated
- 14 Jun 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11435335Frustaci 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.
PubMed 19556262
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01877746
- Acronym / sponsor ID
- ICRC-ICIT-01
- Conditions
- Inflammatory Cardiomyopathy
- Keywords
- ICM, myocarditis, cardiomyopathy, endomyocardial biopsy, immunosuppression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 234 participants (estimated)
- Lead sponsor
- St. Anne's University Hospital Brno, Czech RepublicUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Sep 2015 (estimated)
- Study completion
- Sep 2015 (estimated)
- First posted
- 14 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| R1 - combined immunosuppressive therapy | Experimental | Drug: Combination of prednisone and azathioprineapplication of the combined immunosuppressive therapy in the first dosing regimen |
| R2 - combined immunosuppressive therapy | Experimental | Drug: Combination of prednisone and azathioprineapplication of the combined immunosuppressive therapy in the second dosing regimen |
| S - standard therapy | Other | Other: No interventiononly standard medical therapy of chronic heart failure without application of the combined immunosuppressive therapy |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | R1 - combined immunosuppressive therapy |
| 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. | Drug | R2 - combined immunosuppressive therapy |
| No interventionNo intervention, only standard medical therapy | Other | S - standard therapy |
Primary outcome
comparison of the change in LV ejection fraction
Time frame: baseline and in 12 months after the initiation of immunosuppressive therapy
5 secondary outcomes
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
comparison of the change of New York Heart Association (NYHA) class
Time frame: baseline and in 12 months after the initiation of immunosuppressive therapy
comparison of total mortality
Time frame: baseline and in 12 months after the initiation of immunosuppressive therapy
comparison of the combined end-point
Time frame: baseline and in 12 months after the initiation of immunosuppressive therapy
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2013.
- Background: PubMed 11435335Wojnicz 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.
- Background: PubMed 19556262Frustaci 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Krejci, MD, Ph.D principal investigator
employee
Tomas Palecek, Assoc. prof. principal investigator
without affiliation
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Combination of prednisone and azathioprine in people with Inflammatory Cardiomyopathy, run by St. Anne's University Hospital Brno, Czech Republic at 2 sites in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
comparison of the change in LV ejection fraction (time frame: baseline and in 12 months after the initiation of immunosuppressive therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01877746, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2013.