Immunosuppressive Treatment in Chronic Virus-Negative Inflammatory Cardiomyopathy

• Status: Not yet recruiting
• Trial end date: 2027-04-03
• Target enrollment: 0
• Participant gender: All

Summary

Evaluating Immunosuppressive treatment (Mycophenolate mofetil and prednisolon compared to placebo) for 6 months in patients with chronic virus- Negative Inflammatory cardiomyopathy - a multicenter, randomized, double-blind, placebo-controlled trial.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: LMU Klinikum
• Collaborators: Charite University, Berlin, Germany; Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK); Technical University of Munich; University Hospital Erlangen; University Hospital Tuebingen; University Hospital, Essen
• Treatments: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion Criteria:

1. Age 18-75 years

2. Heart failure NYHA II-III

3. Medical therapy for HF for ≥6 months and <5 years including betablockers, ACE-inhibitors/sartans and/or ARNI, MRA, SGLT2i and diuretics according to current guideline recommendations

4. Persistent reduction of LVEF <45% on a routine echocardiographic evaluation (Simpson's biplane) not older than 1 month at time of inclusion

5. EMB >3 months after first diagnosis of HNDC/DCM and not older than 3 months at time of inclusion with immunohistochemical evidence of lymphocytic myocarditis defined as ≥14 leukocytes/mm2 including up to 4 monocytes/mm2 with the presence of CD3 positive T-lymphocytes ≥7 cells/mm2 and increased MHC-II expression as approved by the histopathology core lab

6. Absence of established cardiotropic virus infection in EMBs (i.e. enteroviruses, HHV-6, EBV, CMV, adenoviruses, parvovirus B19 >500 copies) as approved by the histopathology core lab

7. Negative pregnancy test and the use of a highly effective contraceptive measure in women with child-bearing potential (according to CTFG recommendations)

8. Written informed consent.

Exclusion Criteria:

1. Age <18 or >75 years

2. Histopathological (as approved by the histopathology core lab) and/ or clinical evidence of acute lymphocytic myocarditis, sarcoidosis, GCM or eosinophilic myocarditis

3. Known or possible systemic inflammatory disease

4. Hemodynamic instability/shock

5. Atrial fibrillation with low probability for restoration of a stable sinus rhythm

6. Recent (<3 months) initiation of any of the following medications: betablocker, ACEi/sartans/ARNI, SGLT2-inhibitors, MRA

7. Recent major surgery within <6 weeks, recent ICD implantation within <6 weeks or recent CRT implantation within <6 months prior to baseline examinations

8. Congenital, hypertensive, or valvular heart disease

9. Familial DCM/HNDC (two or more first- or second-degree relatives have DCM or HNDC, or a first-degree relative has autopsy proven DCM and sudden death at <50 years of age)

10. Known coronary artery disease responsible for cardiac dysfunction (i.e. prior myocardial infarction, chronic total occlusion, persistent stenosis >50%)

11. Life expectancy <1 year

12. Therapy with immunosuppression (with comparable regimen) before enrolment

13. Drug or alcohol abuse

14. Pregnancy or lactation

15. Contraindications to immunosuppressive treatment with MMF + corticosteroids (e.g., known allergic reaction to the study drug or any of its components, severe and uncontrollable diabetes mellitus, severe osteoporosis, active peptic ulceration, uncontrolled psychiatric illness, severe liver disease, infectious diseases such as tuberculosis, HIV, viral hepatitis, any history of malignancy)

16. Inability to undergo repetitive MRI scans

17. Inability to provide informed consent

18. Current participation or previous participation in another clinical trial within the preceding 6 months