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

• Status: Not yet recruiting
• Trial end date: 2026-09-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical University of Warsaw
• Treatments: Azathioprine; Prednisone

Criteria

Inclusion Criteria:

To be eligible for inclusion in this study, patient must fulfill all of the following inclusion criteria:

1. Written 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); OR/ AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy who will undergo diagnostic right ventricular EMB during the screening.

3. Men or women aged 18-70. Women of childbearing age must have a negative pregnancy test result. 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 last ≥ 3 months prior to the screening period (V1).

5. LVEF ≤ 45% measured by echocardiogram taken during the screening period (V1)

1. No LVEF improvement in the last ≥3 months prior to the screening period (V1).

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 (V1).

7. Absence of cardiotropic viruses in cardiac tissue at PCR analysis during the screening period (V1).

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, 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. Deficiency or mutation of the enzyme TPMT measured at screening (V1).

3. Positive test for infections: including HIV, HBV, HCV, tuberculosis (Quantiferon), borreliosis.

4. Another specific cause of heart failure (including severe congenital, valvular, hypertensive, and/or coronary artery disease) that could justify the severity of cardiac dysfunction.

5. Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, genetic hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or known pericardial constriction.

6. Subjects with body mass index >40 kg/m2 or body weight <50 kg.

7. Pregnancy, lactation or women who plan to become pregnant during the trial. Lack of consent to the use of effective forms of contraception.

8. Diagnosed or suspected cardiac sarcoidosis or giant cell myocarditis.

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.

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 VAD, CRT or heart transplant recipient.

15. Patients with pacemaker or ICD requiring a high percentage of ventricular pacing (>30%) which could influence the result of LVEF measurement.

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: the presence of non-CMR-compatible pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body that could be contraindication to 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.

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. Persons directly involved in the execution of this protocol.

The investigator may consider re-screening the patient at a later time if believes that the patient's condition has changed and may potentially be eligible. A patient may be re-screened once only.