Patients with biopsy-proven virus-negative inflammatory dilated or non-dilated left ventricular cardiomyopathy and persistent deterioration of cardiac function despite optimal medical treatment (OMT) for heart failure
Conditions
Interventions
Trade Name: Mowel® 500 mg Filmtabletten
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Mycophenolatmofetil
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration num
Sponsors
LMU Klinikum der Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years, 2. Medical therapy for HF at least 3 months but not longer than 10 years according to current guideline recommendations, 3. Persistent reduction of LVEF 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 childbearing potential (according to CTFG recommendations), 7. Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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 baseline examinations, 4. Known coronary artery disease responsible for cardiac dysfunction (i.e., prior myocardial infarction, chronic total occlusion, persistent stenosis =70%), 5. Pregnancy or lactation, 6. Contraindications to immunosuppressive treatment with MMF + corticosteroids, 7. Inability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Two co-primary endpoints (hierarchical testing): 1. Absolute increase in LVEF at 12 months follow-up as assessed by blinded investigators of the MRI core lab (metric endpoint) 2. 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). ;Main Objective: To assess the clinical benefit 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.;Secondary Objective: To assess the clinical benefit with respect to left ventricular function and diameters, quality of life, physical capacity, cardiac autonomic function, transplant-free survival and hospitalization rate, biomarkers and adverse events at 6 and 12 months follow-up. ;Timepoint(s) of evaluation of this end point: Timepoints of evaluation of both co-primary endpoints: 1. Absolute increase in LVEF at 12 months follow-up as assessed by blinded investigators of the MRI core lab (metric endpoint) 2. 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). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Composite clinical outcome: cardiac death, heart transplantation, LVAD implantation 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. 2. Absolute increase in LVEF and rate of increase by =10% at 6 months follow-up (MRI, metric, and binary endpoint). 3. Absolute decrease of left ventricular diameters, volumes, mass and sphericity from baseline to 6 and 12 months follow-up (MRI). 4. Changes in global longitudinal strain from baseline to 6 and 12 months follow-up (MRI). 5. Absolute increase in LVEF and rate of increase by =10% at 6 and 12 months follow-up (echo, metric and binary). 6. Decrease of left ventricular diameters and volumes by =10% at 6 and 12 months follow-up (echo). 7. Changes in global longitudinal (LV), free wall (RV) and left atrial strain (LA) from baseline to 6 and 12 months follow-up (echo). 8. Changes in diastolic parameters from baseline to 6 and 12 months follow-up (echo). 9. Presence of MR/TR >2 at baseline and at 6 and 12 months follow-up (echo). 10. Changes in cardiopulmonary exercise capacity: Distance in the six-minute walk test (6MWT) from baseline to 6 and 12 months follow-up and (optionally) VO2max, anaerobic threshold and VE/VCO2 on spiroergometry. 11. Changes in NYHA functional class from baseline to 6 and 12 months follow-up. 12. Changes in patient-reported outcome (quality of life; QOL) from baseline to follow-up as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). 13. Changes in cardiac autonomic function (PRD, DC) from baseline to 6 and 12 months follow-up. 14. Time to the first occurrence of any of the components of the composite safety outcome: death of any cause, arrhythmias requiring intervention, severe adverse events requiring hospitalization. 15. Time-averaged proportional change in NT-proBNP.;Timepoint(s) of evaluation of this end point: Timepoints of eval | — |
Countries
Germany
Contacts
Public ContactPD Dr. med. Ulrich Grabmaier
Med. Klinik und Poliklinik, LMU Klinikum der Universität München
Outcome results
None listed