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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05570409
Other study ID # TRINITY
Secondary ID
Status Recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date March 28, 2023
Est. completion date March 28, 2028

Study information

Verified date January 2024
Source LMU Klinikum
Contact Ulrich Grabmaier, PD Dr. med.
Phone +49-(0)152-5484-8309
Email ulrich.grabmaier@med.uni-muenchen.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Inflammatory cardiomyopathy constitutes a relevant part of the cohort of hypokinetic non-dilated cardiomyopathy (HNDC)/ 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 hypokinetic non-dilated 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 130
Est. completion date March 28, 2028
Est. primary completion date March 28, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Mycophenolate Mofetil
Mycophenolate mofetil 1g bid for 6 months
Prednisolone
initially 1mg/kg in a step-down regime for 6 months
Mycophenolate Mofetil Placebo
MMF matching Placebo
Prednisolone Placebo
Prednisolone matching placebo

Locations

Country Name City State
Germany Kerckhoff-Klinik GmbH Bad Nauheim
Germany Charité - University Hospital Berlin Berlin
Germany University Hospital Essen Essen
Germany UHF- Universitäres Herz- und Gefässzentrum Frankfurt
Germany University Hospital Freiburg - Bad Krozingen Freiburg
Germany Universitätsmedizin Göttingen Göttingen
Germany University Hospital Greifswald Greifswald
Germany UKE Hamburg Hamburg
Germany University Hospital Heidelberg Heidelberg
Germany Universitäres Herzzentrum Lübeck Lübeck
Germany LMU Klinikum Standort Innenstadt München
Germany Klinikum rechts der Isar Munich
Germany LMU Klinikum Munich
Germany University Hospital Regensburg Regensburg

Sponsors (7)

Lead Sponsor Collaborator
LMU Klinikum Charite University, Berlin, Germany, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Technical University of Munich, University Hospital Erlangen, University Hospital Tuebingen, University Hospital, Essen

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 12 months follow-up
Primary 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). 12 months follow-up
Secondary 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 12 months
Secondary 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). 6 months follow-up
Secondary Ventricular remodelling (MRI) Absolute decrease of left ventricular diameters, volumes, mass, and sphericity from baseline to 6 and 12 months follow-up (MRI). 6 and 12 months follow-up
Secondary Strain (MRI) Changes in global longitudinal, radial, and circumferential strain from baseline to 6 and 12 months follow-up (MRI). 6 and 12 months follow-up
Secondary LVEF increase (echo) Absolute increase in LVEF and rate of increase by =10% at 6 and 12 months follow-up (echo, metric, and binary). 6 and 12 months follow-up
Secondary Ventricular remodelling (echo) Decrease of left ventricular diameters and volumes by =10% at 6 and 12 months follow-up (echo). 6 and 12 months follow-up
Secondary Strain (echo) Changes in global longitudinal, radial, circumferential, early, and late diastolic strain (LV), free wall and septal strain (RV), left atrial strain (LA) from baseline to 6 and 12 months follow-up (echo). 6 and 12 months follow-up
Secondary Diastolic parameters (echo) Changes in diastolic parameters from baseline to 6 and 12 months follow-up (echo). 6 and 12 months follow-up
Secondary Mitral and tricuspid regurgitation (echo) Presence of MR/TR >2 at baseline and at 6 and 12 months followup (echo). 6 and 12 months follow-up
Secondary Cardiopulmonary exercise capacity Changes in cardiopulmonary exercise capacity: Distance in the sixminute walk test (6MWT) from baseline to 6 and 12 months followup and (optionally) VO2max, anaerobic threshold and VE/VCO2 on spiroergometry. 6 and 12 months follow-up
Secondary NYHA Changes in NYHA functional class from baseline to 6 and 12 months follow-up. 6 and 12 months follow-up
Secondary QoL Changes in patient-reported outcome (quality of life; QOL) from baseline to follow-up as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). 12 months
Secondary Cardiac autonomic function Changes in cardiac autonomic function (PRD, DC) from baseline to 6 and 12 months follow-up. 6 and 12 months follow-up
Secondary Composite safety outcome 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. 12 months
Secondary Biomarker Time-averaged proportional change in NT-proBNP 12 months
See also
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Recruiting NCT01877746 - CZECH-ICIT (CZECH Inflammatory Cardiomyopathy Immunosuppression Trial) Phase 3
Recruiting NCT05961202 - The Effects of Hydroxychloroquine in Patients With Inflammatory Cardiomyopathy Phase 2/Phase 3
Recruiting NCT03049254 - Mayo AVC Registry and Biobank
Recruiting NCT04265040 - DZHK TORCH-Plus is a Registry for Patients With Cardiomyopathies and Serves as Source for Cardiovascular Research Studies

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