Immunosuppressive Treatment in Chronic Virus-Negative Inflammatory Cardiomyopathy

Phase 3TerminatedNCT05570409

LMU Klinikum9 enrolled

Overview

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.

Inflammatory cardiomyopathy constitutes a relevant part of the cohort of non-dilated left ventricular cardiomyopathy / dilated cardiomyopathy (DCM) and is associated with adverse outcome. Urgent medical needs remain with respect to the therapeutic options for inflammatory cardiomyopathy. So far, no specific therapy for patients with inflammatory cardiomyopathy is available. Existing data on immunosuppression for inflammatory cardiomyopathy is preliminary and needs further validation by larger randomized, controlled, multicenter trials. Patients with biopsy-proven virus-negative inflammatory dilated or non-dilated left ventricular cardiomyopathy and moderate to severe deterioration of cardiac function despite optimal medical treatment (OMT) for heart failure (HF) will be randomized (1:1) in a double-blinded way to Mycophenolate mofetil (MMF) 1g bid and prednisolone at initially 1mg/kg in a step-down regime for 6 months or placebo. The clinical benefit will be measured with respect to absolute increase in LVEF (metric and binary co-primary endpoints assessed by MRI core lab) of immunosuppressive treatment with MMF and prednisolone compared to placebo at 12 months follow-up.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Inflammatory Cardiomyopathy

Interventions

Mycophenolate MofetilDRUG

Mycophenolate mofetil 1g bid for 6 months

PrednisoloneDRUG

initially 1mg/kg in a step-down regime for 6 months

Mycophenolate Mofetil PlaceboDRUG

MMF matching Placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥18 years 2. Medical therapy for HF for ≥3 months and \<10 years according to current guideline recommendations 3. Persistent reduction of LVEF \<50% on a routine echocardiographic evaluation (Simpson's biplane) not older than 1 month at time of inclusion 4. EMB 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 5. 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 6. Negative pregnancy test and the use of a highly effective contraceptive measure in women with child-bearing potential (according to CTFG recommendations) 7. Written informed consent. Exclusion Criteria: 1. Histopathological (as approved by the histopathology core lab) and/ or clinical evidence of acute lymphocytic myocarditis, sarcoidosis, GCM or eosinophilic myocarditis, 2. Known systemic inflammatory disease, 3. Recent major surgery within \<6 weeks, recent ICD implantation within \<6 weeks or recent CRT implantation within \<3 months prior to, 4. Known coronary artery disease responsible for cardiac dysfunction (i.e., prior myocardial infarction, persistent stenosis ≥ 70%), 5. Pregnancy or lactation, 6. Contraindications to immunosuppressive treatment with MMF + corticosteroids, 7. Inability to provide informed consent.

Locations (14)

Kerckhoff-Klinik GmbH

Bad Nauheim, Germany

Charité - University Hospital Berlin

Berlin, Germany

University Hospital Essen

Essen, Germany

Outcomes

Primary Outcomes

LVEF increase (metric)

Absolute increase in LVEF at 12 months follow-up as assessed by blinded investigators of the MRI core lab (metric endpoint)lab) of immunosuppressive treatment with MMF and prednisolone compared to placebo

Time frame: 12 months follow-up

LVEF increase (binary)

Proportion of patients with an absolute increase in LVEF ≥10% at 12 months follow-up as assessed by blinded investigators of the MRI core lab (binary endpoint).

Time frame: 12 months follow-up

Secondary Outcomes

Composite clinical outcome

Composite clinical outcome: cardiac death, heart transplantation or a heart failure event (hospitalization for heart failure or the equivalent, i.e., an urgent HF visit) within 12 months from randomization, analyzed as time to first event.physical capacity, cardiac autonomic function, transplant-free survival and hospitalization rate, biomarkers and adverse events

Time frame: 12 months

LVEF increase 6 months (MRI)

Absolute increase in LVEF and rate of increase by ≥10% at 6 months follow-up (MRI, metric, and binary endpoint).

Time frame: 6 months follow-up

Ventricular remodelling (MRI)

Absolute decrease of left ventricular diameters, volumes, mass, and sphericity from baseline to 6 and 12 months follow-up (MRI).

Time frame: 6 and 12 months follow-up

Strain (MRI)

Changes in global longitudinal, radial, and circumferential strain from baseline to 6 and 12 months follow-up (MRI).

Time frame: 6 and 12 months follow-up

Data from ClinicalTrials.gov

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