Clinical trial NCT05570409: Immunosuppressive Treatment in Chronic Virus-Negative Inflammatory Cardiomyopathy
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled TRial Evaluating Immunosuppressive Treatment in Patients With Chronic Virus-Negative Inflammatory cardiomyopaThY (TRINITY Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Inflammatory Cardiomyopathy
Keywords: inflammatory cardiomyopathy
heart failure
Mycophenolate mofetil
chronic myocarditis
myocarditis
enomyocardial biopsy
immunosupression
Lead sponsor: LMU Klinikum
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: Technical University of Munich
name: Charite University, Berlin, Germany
name: University Hospital, Essen
name: University Hospital Erlangen
name: University Hospital Tuebingen
First posted: 2022-10-06
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator-initiated, multicenter, randomized, double-blind, placebocontrolled clinical trial
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: LVEF increase (metric)
timeFrame: 12 months follow-up
measure: LVEF increase (binary)
timeFrame: 12 months follow-up
Secondary outcomes:
measure: Composite clinical outcome
timeFrame: 12 months
measure: LVEF increase 6 months (MRI)
timeFrame: 6 months follow-up
measure: Ventricular remodelling (MRI)
timeFrame: 6 and 12 months follow-up
measure: Strain (MRI)
timeFrame: 6 and 12 months follow-up
measure: LVEF increase (echo)
timeFrame: 6 and 12 months follow-up
measure: Ventricular remodelling (echo)
timeFrame: 6 and 12 months follow-up
measure: Strain (echo)
timeFrame: 6 and 12 months follow-up
measure: Diastolic parameters (echo)
timeFrame: 6 and 12 months follow-up
measure: Mitral and tricuspid regurgitation (echo)
timeFrame: 6 and 12 months follow-up
measure: Cardiopulmonary exercise capacity
timeFrame: 6 and 12 months follow-up
measure: NYHA
timeFrame: 6 and 12 months follow-up
measure: QoL
timeFrame: 12 months
measure: Cardiac autonomic function
timeFrame: 6 and 12 months follow-up
measure: Composite safety outcome
timeFrame: 12 months
measure: Biomarker
timeFrame: 12 months
Other outcomes:
Locations:
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik GmbH
city: Berlin
country: Germany
facility: Charité - University Hospital Berlin
city: Essen
country: Germany
facility: University Hospital Essen
city: Frankfurt
country: Germany
facility: UHF- Universitäres Herz- und Gefässzentrum
city: Freiburg
country: Germany
facility: University Hospital Freiburg - Bad Krozingen
city: Greifswald
country: Germany
facility: University Hospital Greifswald
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Hamburg
country: Germany
facility: UKE Hamburg
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Lübeck
country: Germany
facility: Universitäres Herzzentrum Lübeck
city: Munich
country: Germany
facility: Klinikum rechts der Isar
city: Munich
country: Germany
facility: LMU Klinikum
city: München
country: Germany
facility: LMU Klinikum Standort Innenstadt
city: Regensburg
country: Germany
facility: University Hospital Regensburg
Study officials:
affiliation: LMU Klinikum
name: Urlich Grabmaier, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: