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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 4INTERVENTIONAL

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

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

Study to Evaluate the Efficacy of Immunosuppression in Myocarditis or Inflammatory Cardiomyopathy. (NCT04654988) is a Phase 4 interventional studying Myocarditis and Heart Failure, sponsored by Medical University of Warsaw. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 100 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Myocarditis subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: To be eligible for inclusion in this study, patient must fulfill all of the following Who May Qualify: 1. Written willing to sign a consent form to participate in the IMPROVE-MC study (including two EMBs and two cardiac CMRs) prior to any evaluation or procedure related to the study. 2. 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. 3. 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: To be eligible for inclusion in this study, patient must fulfill all of the following inclusion criteria: 1. 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. 2. 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. 3. 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. 4. 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. 5. LVEF 10 - 45% measured by echocardiogram taken during the screening period 1. No significant LVEF improvement in the last ≥3 months prior to the screening period in the investigator's opinion. 2. LVEF should be measured under stable conditions as assessed by the investigator. 3. LVEF should be verified in the CORE-LAB. 6. 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). 7. Absence of cardiotropic viruses in cardiac tissue at PCR analysis during the screening period (EMB during the screening or within last 3 months). Exclusion Criteria: 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. 1. 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). 2. 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. 3. Another specific cause of heart failure (including severe congenital, valvular, hypertensive, and/or coronary artery disease) that could justify the severity of cardiac dysfunction. 4. 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. 5. 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). 6. NYHA class I and IV. 7. Subjects with body mass index \>40 kg/m2 or body weight \<50 kg. 8. Pregnancy, lactation or women who plan to become pregnant during the trial. Lack of consent to the use of effective forms of contraception. 9. Any documented or suspected active malignant neoplasm or history of malignant neoplasm within the 5 years prior to the screening period. 10. History of cytostatic therapy or radiotherapy. 11. Liver disease defined as any of the following: AST or ALT or ALP above 3x ULN; bilirubin \>1.5 mg/dL. 12. 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. 13. The need or refusal to stop taking any drug considered to interfere with the safe course of the study (e.g., allopurinol). 14. Currently implanted or planned VAD, CRT or heart transplant. 15. 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. 16. Gastrointestinal surgery or gastrointestinal disorder that could interfere with trial drug(s) absorption in the investigator's opinion. 17. History or presence of any other disease with a life expectancy \<3 years. 18. Any contraindications or intolerance to CMR\*, including but not limited to: 1. the presence of cardiac implantable electronic device implanted \<6 weeks ago; 2. pacing capture threshold out of the normal range; 3. additional cardiac leads (particularly abandoned pacemaker leads), epicardial leads, fractured leads, additional components such as lead adapters or lead extension; 4. aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body that could be contraindication to CMR; 5. presence of claustrophobia making impossible to perform CMR; 6. 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. 19. Immunization with live organism vaccines in the last 3 months prior to randomization. 20. 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. 21. Use of other investigational drugs at the time of enrollment, or within 30 days, or within 5 half-lives of enrollment, whichever is longer. 22. 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

Treatments Being Tested

DRUG

Prednisone

Prednisone: 1 mg/kg daily for 4 weeks followed by gradually tapered dose for 5 months

DRUG

Azathioprine

Azathioprine: 2 mg/kg daily for 12 months

DRUG

Placebo Prednisone

Placebo Prednisone

DRUG

Placebo Azathioprine

Placebo Azathioprine

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

First Department of Cardiology, Medical University of Warsaw
Warsaw, Poland

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04654988), the sponsor (Medical University of Warsaw), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04654988 clinical trial studying?

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 a… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04654988?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04654988?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04654988. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04654988. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.