Inflammatory Cardiomyopathy Clinical Trial
— TRINITYOfficial title:
A Multicenter, Randomized, Double-blind, Placebo-controlled TRial Evaluating Immunosuppressive Treatment in Patients With Chronic Virus-Negative Inflammatory cardiomyopaThY (TRINITY Trial)
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.
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 |
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 |
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 |
Germany,
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 |
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