MyocarditisPhase 4IMPROVE-MCNCT04654988

Study to Evaluate the Efficacy of Immunosuppression in Myocarditis or Inflammatory Cardiomyopathy.

A Phase 4 study testing Prednisone and Azathioprine in people with Myocarditis and Heart Failure, run by Medical University of Warsaw at 1 site in Poland.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Myocarditis, Heart Failure, Endomyocardial Biopsy
What is being tested?: Prednisone and Azathioprine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 100 participants
Where: 1 sitePoland
Study dates: 1 Dec 2022to 30 Mar 2028
Phase: Phase 4
Are there results?: Not yet: the study is under way

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

To be eligible for inclusion in this study, patient must fulfill all of the following inclusion criteria:
Written informed consent to participate in the IMPROVE-MC study (including two EMBs and two cardiac CMRs) prior to any evaluation or procedure related to the study.
Patient with clinically suspected myocarditis or inflammatory cardiomyopathy (according to the criteria of the ESC Working Group on Myocardial \& Pericardial Diseases 2013 and ESC Heart Failure Guidelines 2021); OR/ AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy who will undergo diagnostic right ventricular (or/and left ventricular) EMB during the screening; OR / AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy confirmed by right ventricular (or/and left ventricular) EMB that was performed according to the IMPROVE-MC study protocol within 3 months from screening.
Men or women aged 18-65. Women of childbearing age must have a negative pregnancy test result. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (with a failure rate of < 1% per year) for the duration of the study (from the time they sign consent) and for 8 weeks after the last dose of study treatment to prevent pregnancy. Patients agreeing to total sexual abstinence can also be included, assuming it is their usual lifestyle. Women are considered postmenopausal and without the potential to have a child if they have 12 months of natural (spontaneous) amenorrhea with an appropriate clinical picture (e.g. appropriate age, history of vasomotor symptoms) or have undergone bilateral surgical ovariectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of ovariectomy alone, only if the reproductive status of the woman has been confirmed by assessing hormone levels.
No significant improvement in clinical condition or worsening course of the disease despite the standard treatment in the investigator's opinion, in the last ≥ 3 months prior to the screening period.
LVEF 10 - 45% measured by echocardiogram taken during the screening period

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No significant LVEF improvement in the last ≥3 months prior to the screening period in the investigator's opinion.
LVEF should be measured under stable conditions as assessed by the investigator.
LVEF should be verified in the CORE-LAB.
Histological and immunohistochemical evidence of active myocarditis (lymphocytic or eosinophilic) OR inflammatory cardiomyopathy during the screening period (EMB during the screening or within last 3 months).
Absence of cardiotropic viruses in cardiac tissue at PCR analysis during the screening period (EMB during the screening or within last 3 months).

Who cannot join

Patients fulfilling any of the following exclusion criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.
Presence of contraindications to immunosuppressive therapy with steroids and/ or azathioprine (including hypersensitivity to azathioprine/ 6-mercaptopurine or prednisone, mainly untreated systemic infection, uncontrolled diabetes, poorly controlled endocrine diseases, osteoporosis, active gastric or duodenal ulcer, uncontrolled hypertension, leukocytopenia (leukocyte counts <4 x 109/l), neutropenia (neutrophils <1.5 x 109/l), thrombocytopenia (platelet levels <130 x 109/l), anemia (hemoglobin levels <11 g/dl).
Positive clinical screening for active infections, including HIV, HBV, HCV. Assessment of tuberculosis infection should be considered before screening, according to the local epidemiologic status and according to investigator's opinion. After careful evaluation of the activity of the infection (or cure of the infection), the patient may continue participation in the study according to investigator's opinion.
Another specific cause of heart failure (including severe congenital, valvular, hypertensive, and/or coronary artery disease) that could justify the severity of cardiac dysfunction.
Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), storage diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, genetic hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or known pericardial constriction.
Diagnosed or suspected cardiac sarcoidosis or giant cell myocarditis, autoimmune/ systemic immune-mediated disease (i.e. granulomatosis with polyangiitis, lupus erythematosus) that might require specific immunosuppressive therapy. Recent, current or expected future need for long-term use of immunosuppressive therapy with steroids and/ or azathioprine and/ or other immunosuppressive agent (caution - short-term course of steroids [i.e. for asthma attack, occasional topical applications] is not an exclusion).

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NYHA class I and IV.
Subjects with body mass index >40 kg/m2 or body weight <50 kg.
Pregnancy, lactation or women who plan to become pregnant during the trial. Lack of consent to the use of effective forms of contraception.
Any documented or suspected active malignant neoplasm or history of malignant neoplasm within the 5 years prior to the screening period.
History of cytostatic therapy or radiotherapy.
Liver disease defined as any of the following: AST or ALT or ALP above 3x ULN; bilirubin >1.5 mg/dL.
Impaired renal function, defined as eGFR <45 mL / min / 1.73 m2 (CKD-EPI) measured under stable condition or requiring dialysis. Conditionally, according to the investigator's decision, patients with eGFR 40-45 ml / min / 1.73 m2 may be included.
The need or refusal to stop taking any drug considered to interfere with the safe course of the study (e.g., allopurinol).
Currently implanted or planned VAD, CRT or heart transplant.
Patients with pacemaker or ICD requiring a high percentage of ventricular pacing (>30%) which could influence the result of LVEF measurement in the investigator's opinion.
Gastrointestinal surgery or gastrointestinal disorder that could interfere with trial drug(s) absorption in the investigator's opinion.
History or presence of any other disease with a life expectancy <3 years.
Any contraindications or intolerance to CMR*, including but not limited to:
the presence of cardiac implantable electronic device implanted <6 weeks ago;
pacing capture threshold out of the normal range;
additional cardiac leads (particularly abandoned pacemaker leads), epicardial leads, fractured leads, additional components such as lead adapters or lead extension;
aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body that could be contraindication to CMR;
presence of claustrophobia making impossible to perform CMR;
or any other clinical history or study that determines that, in the investigator's judgment, the performance of an CMR may pose a potential risk to the patient.
Immunization with live organism vaccines in the last 3 months prior to randomization.
Chronic alcohol or drug abuse or non-compliance with medical recommendations or any condition that, in the investigator's opinion, makes patient an unreliable trial subject or unlikely to complete the trial.
Use of other investigational drugs at the time of enrollment, or within 30 days, or within 5 half-lives of enrollment, whichever is longer.
Subjects directly involved in the execution of this protocol.
CMR in non-conditional CIED proved to be safe. CMR in CIED patients will be performed according to HRS 2017 and ESC Pacing 2021 guidelines

Trial locations and contacts

1 site in 1 country.

Poland1 site

First Department of Cardiology, Medical University of Warsaw
Warsaw, 02-097

Other trials in Poland

About this study

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Immunosuppression in Biopsy-proven Virus Negative Myocarditis or Inflammatory Cardiomyopathy

Myocarditis can result in numerous complications, but there is paucity of data regarding optimal therapy, short- and long-term effects of possibly effective immunosuppressive therapy. The IMPROVE-MC study will provide high-quality scientific data about efficacy and safety of immunosuppressive therapy, non-invasive (MRI, biomarkers) and invasive diagnostics tests (endomyocardial biopsy), and prognosis in myocarditis. The objective of this multicenter, prospective, randomized, double-blind placebo-controlled trial is to assess the efficacy and safety of 12 - month treatment with prednisone and azathioprine comparing to placebo on top of guideline-recommended medical therapy in patients with biopsy-proven virus negative myocarditis or inflammatory cardiomyopathy and reduced ejection fraction (LVEF ≤ 45%). The study will also assess persistence of the treatment effects after 12 months.

Read the detailed description

Myocarditis/ inflammatory cardiomyopathy, which often leads to heart failure (HF), is still an under-studied disease with various clinical manifestations. The active myocarditis is found post-mortem even in 42% of sudden deaths of young people and in 9-16% of adults and 46% of children with idiopathic dilated cardiomyopathy. Moreover, an increase in morbidity and mortality from myocarditis was recorded in the years 1990-2015. Myocarditis significantly increases the risk of HF, serious arrhythmias and conduction abnormalities, sudden death, anxiety, depression and it reduces quality of life. Myocarditis affects mainly young people (18-40 years old, and children) who lead active family life and work. Therefore, the disease causes deterioration of entire family life, it reduces individual productivity, creates high and long-term treatment costs. There is an urgent need to improve myocarditis therapy. Current guidelines recommendations in myocarditis consists of standard treatment of already developed HF and long-term avoidance of physical activity. Due to the lack of good quality scientific data, there is no clear recommendation for the targeted treatment - thus patients' prognosis may be poor. The pathogenesis of myocarditis and limited reports suggest the reasonable chance of significant improvement of patients' survival due to immunosuppressive therapy.

Aim: Aim of the IMPROVE-MC study is to assess the efficacy and safety of 12-month immunosuppressive treatment with prednisone and azathioprine compared with placebo on the guideline-recommended medical therapy in patients with biopsy-proven virus-negative myocarditis or inflammatory cardiomyopathy. Secondary aim is to create ready-to-use diagnostic and therapeutic scheme in polish and international healthcare systems, which can lead to myocarditis guidelines change.

Population and methods: In this multicenter (7 recruitment centers), prospective, randomized, double-blind placebo-controlled trial we are going to include 100 patients aged 18-65 years old, with biopsy-proven virus-negative myocarditis in stable or worsening course of the disease despite standard medical treatment, with left ventricular ejection fraction (LVEF) ≤45% and/or significant cardiac arrhythmias refractory to antiarrhythmic treatment.

Exclusion criteria consist of ie.: another specific etiology of HF different from myocarditis; already implanted ventricular assist device; a heart transplant recipient; contraindications to immunosuppressive treatment; suspected sarcoidosis or giant cell myocarditis.

Intervention: azathioprine for 12 months and prednisone for the first 6 months versus placebo for 12 months Study course: after randomization patients will undergo one-year double-blind treatment and then one-year follow-up to assess the long-term effects of the treatment.

The efficacy and safety of the treatment will be assessed during study visits: investigational products/ placebo will be provided and additional tests will be performed - 48-hour Holter monitoring, echocardiography, cardiac magnetic resonance imaging (CMR), laboratory tests and follow-up endomyocardial biopsy (EMB) after one-year of treatment. In order to broaden knowledge about myocarditis pathogenesis additional genetic, immunology and proteomic tests will be performed. All echo, MRI, Holter and biopsy tests will be evaluated centrally.

Study endpoints:

primary endpoint is LVEF at 12-months. secondary endpoints include analysis of: e.g. clinical outcomes, echocardiography, CMR, EMB, laboratory examinations, quality of life and heart failure questionnaires.

Conditions: Myocarditis, Heart Failure, Endomyocardial Biopsy, Cardiomyopathies, Secondary, Immunosuppression
Being tested: Prednisone, Azathioprine, Placebo Prednisone, Placebo Azathioprine
Keywords: myocarditis, cardiomyopathy, immunosuppression, biopsy
Medical subject headings: Myocarditis, Heart Failure, Cardiomyopathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PrednisoneDrug
Prednisone: 1 mg/kg daily for 4 weeks followed by gradually tapered dose for 5 months
AzathioprineDrug
Azathioprine: 2 mg/kg daily for 12 months
Placebo PrednisoneDrug
Placebo Prednisone
Placebo AzathioprineDrug
Placebo Azathioprine

Study groups in NCT04654988
Study group	Role	What they receive
Immunosuppression	Experimental	Prednisone: 1 mg/kg daily for 4 weeks followed by gradually tapered dose for 5 months and Azathioprine: 2 mg/kg daily for 12 months Receives: Drug: Prednisone; Drug: Azathioprine
Placebo	Placebo comparator	placebo matching prednisone: 1 mg/kg daily for 4 weeks followed by gradually tapered dose for 5 months and placebo matching azathioprine: 2 mg/kg daily for 12 months Receives: Drug: Placebo Prednisone; Drug: Placebo Azathioprine

What is being measured

The primary outcome is the main question the study is designed to answer.

LVEF at 12 - months.
Left ventricle ejection fraction (LVEF) at 12 - months.
Measured: 12- months

Secondary outcomes (48)

Proportion of patients who responded to immunosuppressive therapy.
Proportion of patients who responded to immunosuppressive therapy as defined by an LVEF increase of ≥10% over time.
Measured: 12-months
LVEF at 12 months in subgroups of patients with baseline LVEF ≤30% and >30%
Measured: 12 months
Change in the LV end-systolic and end-diastolic dimensions as well as the LV end-systolic and end-diastolic volumes over time.
Measured: 12-months
Change from baseline in NYHA class over time.
Measured: 12-months
Occurrence of adjudicated heart failure decompensation (hospitalization or ambulatory visit).
Measured: 12-months
Change from baseline in percentage of patients in NYHA III/IV and NYHA II class over time.
Change from baseline in percentage of patients in NYHA III/IV and NYHA II class over time (compared to baseline and to the end of treatment)
Measured: assessed up to 24th month from the randomization
Occurrence of need for diuretic i.v. administration.
Measured: assessed up to 24th month from the randomization
Change from baseline in 6 minute walk test (6MWT) distance over time.
Measured: assessed up to 24th month from the randomization
Time to first adjudicated hospitalization for heart failure.
Measured: assessed up to 24th month from the randomization
Time to first all-cause hospitalization.
Measured: assessed up to 24th month from the randomization
Occurrence (first and recurrent) of all-cause hospitalization, heart failure hospitalization, heart failure outpatient visit, myocarditis or inflammatory cardiomyopathy recurrence, all-cause death, heart transplantation, implantation of cardiac device
Occurrence (first and recurrent) of all-cause hospitalization, heart failure hospitalization, heart failure outpatient visit, myocarditis or inflammatory cardiomyopathy recurrence, all-cause death, heart transplantation, implantation of cardiac device (pacemaker, implantable cardioverter-defibrillator, cardiac resynchronization therapy, ventricular assist device) assessed in combination or independently.
Measured: assessed up to 24th month from the randomization
New onset atrial fibrillation (AF).
Measured: assessed up to 24th month from the randomization
New onset sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).
Measured: assessed up to 24th month from the randomization
≥50% reduction from baseline in ventricular ectopic beats (VEBs) number in 48h Holter monitoring over time.
Measured: assessed up to 24th month from the randomization
≥50% reduction from baseline in nonsustained VT number in 48h Holter monitoring over time.
Measured: assessed up to 24th month from the randomization
≥50% reduction from baseline in AF burden in 48h Holter monitoring over time.
Measured: assessed up to 24th month from the randomization
Changes from baseline in CMR results
Changes from baseline in CMR results (early gadolinum enhancement (EGE), late gadolinum enhancement (LGE), edema, LV dimensions and volumes, T1/T2 mapping) after one-year.
Measured: assessed up to 24th month from the randomization
Changes from baseline in concentration of biomarkers of fibrosis and myocardial necrosis (troponin I, NT-proBNP, sST2, Gal-3) over time.
Measured: assessed up to 24th month from the randomization
Qualitative and quantitative change from baseline in inflammatory infiltration, human leukocyte antigen (HLA) expression and fibrosis in EMB after one-year.
Measured: after 12- months
Change from baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) overall summary score over time.
Measured: assessed up to 24th month from the randomization
Change from baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) total symptom score over time.
Measured: assessed up to 24th month from the randomization
Change from baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) individual domains over time.
Measured: assessed up to 24th month from the randomization
Change from baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) based on patient-preferred outcome over time.
Measured: assessed up to 24th month from the randomization
Change from baseline in SF-36 (36-Item Short Form Survey) questionnaire overall summary score over time.
Measured: assessed up to 24th month from the randomization
Change from baseline in PGI-I (Patients Global Impression of Improvement) scale over time.
Measured: assessed up to 24th month from the randomization
Change from baseline in CGI-I (Clinical Global Impressions - Improvement) scale over time.
Measured: assessed up to 24th month from the randomization
Change from baseline in health economic analysis by HCRU (Healthcare Resource Utilization).
Measured: assessed up to 24th month from the randomization
Occurrence of need for inotropic drugs/nitroglycerin i.v. administration
Occurrence of need for inotropic drugs/nitroglycerin i.v. administration
Measured: assessed up to 24th month from the randomization
LVEF at 24 months
LVEF at 24 months (maintenance or further improvement).
Measured: compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months)
LVEF at 24 months in subgroups of patients with baseline LVEF ≤30% and >30%
LVEF at 24 months (maintenance or further improvement) in subgroups of patients with baseline LVEF ≤30% and >30%
Measured: compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months)
Change in the LV end-systolic and end-diastolic dimensions as well as the LV end-systolic and end-diastolic volumes over time.
Measured: compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months)
Change in NYHA class over time
Measured: compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months)
Occurrence of adjudicated heart failure decompensation (hospitalization or ambulatory visit).
Measured: analyzed during follow up (13-24 months)
Application of mechanical circulatory support (i.e. ECMO).
Measured: assessed up to 24th month from the randomization
≥50% increase from the end of treatment in VEBs number in 48h Holter monitoring over time.
Measured: assessed from the end of treatment up to 24th months from the randomization
≥50% increase from the end of treatment in nonsustained VT number in 48h Holter monitoring over time
Measured: assessed from the end of treatment up to 24th months from the randomization
≥50% increase from the end of treatment in AF burden in 48h Holter monitoring over time
Measured: assessed from the end of treatment up to 24th months from the randomization
Changes in tricuspid annular plane systolic excursion
Changes in tricuspid annular plane systolic excursion (reported in centimeters) over time.
Measured: assessed up to 24th months from the randomization
Changes in dimensions of the heart cavities
Changes in dimensions of the heart cavities (ventricles and atria; reported in centimeters) over time.
Measured: assessed up to 24th months from the randomization
Changes in volumes of the heart cavities
Changes in volumes of the heart cavities (ventricles and atria; reported in milliliters) over time.
Measured: assessed up to 24th months from the randomization
Changes in thickness of left and right ventricles
Changes in thickness of left and right ventricles (reported in centimeters) over time.
Measured: assessed up to 24th months from the randomization
Changes in tissue Doppler velocities (medial and lateral) of the mitral annulus
Tissue Doppler velocities (medial and lateral) of the mitral annulus (reported in centimeters per second) over time.
Measured: assessed up to 24th months from the randomization
Changes in strain of heart cavities
Changes in strain of heart cavities (ventricles and atria; reported as a percentage) over time.
Measured: assessed up to 24th months from the randomization
Changes in concentration of biomarkers of fibrosis and myocardial necrosis (troponin I, NT-proBNP) over time
Measured: assessed up to 24th months from the randomization
Changes in concentration of anti-heart autoantibodies (AHA) over time
Measured: assessed up to 24th months from the randomization
Change of patients' health status as assessed by the patients self-reported EQ-5D over time.
Measured: assessed up to 24th months from the randomization
Change in clinical summary score (heart failure symptoms and physical limitations domains) of KCCQ Questionnaire over time
Measured: assessed up to 24th months from the randomization
Cost-effectiveness analysis
Pharmacoeconomic analysis based on questionnaires (SF-36, KCCQ, EQ-5D-5L, PGI, CGI, HCRU) and patient prognosis (including adverse event rates, hospitalizations, death, worsening of heart failure, arrhythmias, drug-related adverse events, change in LVEF and NYHA class, gain of QALY).
Measured: assessed up to 24th months from the randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Dec 202230 Mar 2028

First posted4 Dec 2020
Study start1 Dec 2022
Primary completion30 Sep 2027 (estimated)
Study completion30 Mar 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for MyocarditisStudies of the same condition, open and under way.
More trials run by Medical University of WarsawThe sponsor's other registered studies.
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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 100 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04654988
Sponsor's protocol ID: PREDAZA/WUM/10-09-2020
Other IDs: 2020-003877-23
Acronym: IMPROVE-MC
Status last verified: Sep 2026
First submitted: 3 Dec 2020
Last updated: 22 Sep 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: the study documents will be available on demand

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Myocarditis trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Immunosuppression in Biopsy-proven Virus Negative Myocarditis or Inflammatory Cardiomyopathy
ClinicalTrials.gov ID: NCT04654988
Acronym / sponsor ID: IMPROVE-MC / PREDAZA/WUM/10-09-2020
Conditions: Myocarditis, Heart Failure, Endomyocardial Biopsy, Cardiomyopathies, Secondary, Immunosuppression
Keywords: myocarditis, cardiomyopathy, immunosuppression, biopsy
Phase: Phase 4
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 100 participants (estimated)
Lead sponsor: Medical University of WarsawUniversity, hospital or other
Study start: 1 Dec 2022 (actual)
Primary completion: 30 Sep 2027 (estimated)
Study completion: 30 Mar 2028 (estimated)
First posted: 4 Dec 2020 (actual)
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.

Detailed description

Study endpoints:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Immunosuppression	Experimental	Drug: Prednisone, Drug: AzathioprinePrednisone: 1 mg/kg daily for 4 weeks followed by gradually tapered dose for 5 months and Azathioprine: 2 mg/kg daily for 12 months
Placebo	Placebo comparator	Drug: Placebo Prednisone, Drug: Placebo Azathioprineplacebo matching prednisone: 1 mg/kg daily for 4 weeks followed by gradually tapered dose for 5 months and placebo matching azathioprine: 2 mg/kg daily for 12 months

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

To be eligible for inclusion in this study, patient must fulfill all of the following inclusion criteria:
Written informed consent to participate in the IMPROVE-MC study (including two EMBs and two cardiac CMRs) prior to any evaluation or procedure related to the study.
Patient with clinically suspected myocarditis or inflammatory cardiomyopathy (according to the criteria of the ESC Working Group on Myocardial \& Pericardial Diseases 2013 and ESC Heart Failure Guidelines 2021); OR/ AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy who will undergo diagnostic right ventricular (or/and left ventricular) EMB during the screening; OR / AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy confirmed by right ventricular (or/and left ventricular) EMB that was performed according to the IMPROVE-MC study protocol within 3 months from screening.
Men or women aged 18-65. Women of childbearing age must have a negative pregnancy test result. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (with a failure rate of < 1% per year) for the duration of the study (from the time they sign consent) and for 8 weeks after the last dose of study treatment to prevent pregnancy. Patients agreeing to total sexual abstinence can also be included, assuming it is their usual lifestyle. Women are considered postmenopausal and without the potential to have a child if they have 12 months of natural (spontaneous) amenorrhea with an appropriate clinical picture (e.g. appropriate age, history of vasomotor symptoms) or have undergone bilateral surgical ovariectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of ovariectomy alone, only if the reproductive status of the woman has been confirmed by assessing hormone levels.
No significant improvement in clinical condition or worsening course of the disease despite the standard treatment in the investigator's opinion, in the last ≥ 3 months prior to the screening period.

Key exclusion criteria (30 listed)

Patients fulfilling any of the following exclusion criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.
Presence of contraindications to immunosuppressive therapy with steroids and/ or azathioprine (including hypersensitivity to azathioprine/ 6-mercaptopurine or prednisone, mainly untreated systemic infection, uncontrolled diabetes, poorly controlled endocrine diseases, osteoporosis, active gastric or duodenal ulcer, uncontrolled hypertension, leukocytopenia (leukocyte counts <4 x 109/l), neutropenia (neutrophils <1.5 x 109/l), thrombocytopenia (platelet levels <130 x 109/l), anemia (hemoglobin levels <11 g/dl).
Positive clinical screening for active infections, including HIV, HBV, HCV. Assessment of tuberculosis infection should be considered before screening, according to the local epidemiologic status and according to investigator's opinion. After careful evaluation of the activity of the infection (or cure of the infection), the patient may continue participation in the study according to investigator's opinion.
Another specific cause of heart failure (including severe congenital, valvular, hypertensive, and/or coronary artery disease) that could justify the severity of cardiac dysfunction.
Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), storage diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, genetic hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or known pericardial constriction.

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
PrednisonePrednisone: 1 mg/kg daily for 4 weeks followed by gradually tapered dose for 5 months	Drug	Immunosuppression
AzathioprineAzathioprine: 2 mg/kg daily for 12 months	Drug	Immunosuppression
Placebo PrednisonePlacebo Prednisone	Drug	Placebo
Placebo AzathioprinePlacebo Azathioprine	Drug	Placebo

Primary outcome

LVEF at 12 - months.
Time frame: 12- months
Left ventricle ejection fraction (LVEF) at 12 - months.

48 secondary outcomes

Proportion of patients who responded to immunosuppressive therapy.
Time frame: 12-months
LVEF at 12 months in subgroups of patients with baseline LVEF ≤30% and >30%
Time frame: 12 months
Change in the LV end-systolic and end-diastolic dimensions as well as the LV end-systolic and end-diastolic volumes over time.
Time frame: 12-months
Change from baseline in NYHA class over time.
Time frame: 12-months
Occurrence of adjudicated heart failure decompensation (hospitalization or ambulatory visit).
Time frame: 12-months
Change from baseline in percentage of patients in NYHA III/IV and NYHA II class over time.
Time frame: assessed up to 24th month from the randomization
Occurrence of need for diuretic i.v. administration.
Time frame: assessed up to 24th month from the randomization
Change from baseline in 6 minute walk test (6MWT) distance over time.
Time frame: assessed up to 24th month from the randomization
Time to first adjudicated hospitalization for heart failure.
Time frame: assessed up to 24th month from the randomization
Time to first all-cause hospitalization.
Time frame: assessed up to 24th month from the randomization
Occurrence (first and recurrent) of all-cause hospitalization, heart failure hospitalization, heart failure outpatient visit, myocarditis or inflammatory cardiomyopathy recurrence, all-cause death, heart transplantation, implantation of cardiac device
Time frame: assessed up to 24th month from the randomization
New onset atrial fibrillation (AF).
Time frame: assessed up to 24th month from the randomization
New onset sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).
Time frame: assessed up to 24th month from the randomization
≥50% reduction from baseline in ventricular ectopic beats (VEBs) number in 48h Holter monitoring over time.
Time frame: assessed up to 24th month from the randomization
≥50% reduction from baseline in nonsustained VT number in 48h Holter monitoring over time.
Time frame: assessed up to 24th month from the randomization
≥50% reduction from baseline in AF burden in 48h Holter monitoring over time.
Time frame: assessed up to 24th month from the randomization
Changes from baseline in CMR results
Time frame: assessed up to 24th month from the randomization
Changes from baseline in concentration of biomarkers of fibrosis and myocardial necrosis (troponin I, NT-proBNP, sST2, Gal-3) over time.
Time frame: assessed up to 24th month from the randomization
Qualitative and quantitative change from baseline in inflammatory infiltration, human leukocyte antigen (HLA) expression and fibrosis in EMB after one-year.
Time frame: after 12- months
Change from baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) overall summary score over time.
Time frame: assessed up to 24th month from the randomization
Change from baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) total symptom score over time.
Time frame: assessed up to 24th month from the randomization
Change from baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) individual domains over time.
Time frame: assessed up to 24th month from the randomization
Change from baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) based on patient-preferred outcome over time.
Time frame: assessed up to 24th month from the randomization
Change from baseline in SF-36 (36-Item Short Form Survey) questionnaire overall summary score over time.
Time frame: assessed up to 24th month from the randomization
Change from baseline in PGI-I (Patients Global Impression of Improvement) scale over time.
Time frame: assessed up to 24th month from the randomization
Change from baseline in CGI-I (Clinical Global Impressions - Improvement) scale over time.
Time frame: assessed up to 24th month from the randomization
Change from baseline in health economic analysis by HCRU (Healthcare Resource Utilization).
Time frame: assessed up to 24th month from the randomization
Occurrence of need for inotropic drugs/nitroglycerin i.v. administration
Time frame: assessed up to 24th month from the randomization
LVEF at 24 months
Time frame: compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months)
LVEF at 24 months in subgroups of patients with baseline LVEF ≤30% and >30%
Time frame: compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months)
Change in the LV end-systolic and end-diastolic dimensions as well as the LV end-systolic and end-diastolic volumes over time.
Time frame: compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months)
Change in NYHA class over time
Time frame: compared to baseline and/or to the end of treatment) analyzed during follow up (13-24 months)
Occurrence of adjudicated heart failure decompensation (hospitalization or ambulatory visit).
Time frame: analyzed during follow up (13-24 months)
Application of mechanical circulatory support (i.e. ECMO).
Time frame: assessed up to 24th month from the randomization
≥50% increase from the end of treatment in VEBs number in 48h Holter monitoring over time.
Time frame: assessed from the end of treatment up to 24th months from the randomization
≥50% increase from the end of treatment in nonsustained VT number in 48h Holter monitoring over time
Time frame: assessed from the end of treatment up to 24th months from the randomization
≥50% increase from the end of treatment in AF burden in 48h Holter monitoring over time
Time frame: assessed from the end of treatment up to 24th months from the randomization
Changes in tricuspid annular plane systolic excursion
Time frame: assessed up to 24th months from the randomization
Changes in dimensions of the heart cavities
Time frame: assessed up to 24th months from the randomization
Changes in volumes of the heart cavities
Time frame: assessed up to 24th months from the randomization

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
Individual participant dataSharing planned: Yes. the study documents will be available on demand

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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.

Marcin Grabowski, Professor study chair

Medical University of Warsaw

Krzysztof Ozierański, MD, PhD principal investigator

Medical University of Warsaw

Agata Tymińska, MD, PhD principal investigator

Medical University of Warsaw

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Prednisone and Azathioprine in people with Myocarditis and Heart Failure, run by Medical University of Warsaw at 1 site in Poland.

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 11 inclusion and 30 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: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Poland. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

LVEF at 12 - months. (time frame: 12- months). 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 NCT04654988.

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 22 Sep 2026.