Inflammatory CardiomyopathyPhase 2/3TRINITYNCT05570409
Immunosuppressive Treatment in Chronic Virus-Negative Inflammatory Cardiomyopathy
A Phase 2/3 study testing Mycophenolate Mofetil and Prednisolone in people with Inflammatory Cardiomyopathy, run by LMU Klinikum at 14 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammatory Cardiomyopathy
- What is being tested?
- Mycophenolate Mofetil and Prednisolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 14 sitesGermany
- Study dates
- 28 Mar 2023to 14 Apr 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Medical therapy for HF for ≥3 months and <10 years according to current guideline recommendations
- Persistent reduction of LVEF <50% on a routine echocardiographic evaluation (Simpson's biplane) not older than 1 month at time of inclusion
- 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
- 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
- Negative pregnancy test and the use of a highly effective contraceptive measure in women with child-bearing potential (according to CTFG recommendations)
- Written informed consent.
Who cannot join
- Histopathological (as approved by the histopathology core lab) and/ or clinical evidence of acute lymphocytic myocarditis, sarcoidosis, GCM or eosinophilic myocarditis,
- Known systemic inflammatory disease,
- Recent major surgery within <6 weeks, recent ICD implantation within <6 weeks or recent CRT implantation within <3 months prior to,
- Known coronary artery disease responsible for cardiac dysfunction (i.e., prior myocardial infarction, persistent stenosis ≥ 70%),
- Pregnancy or lactation,
- Contraindications to immunosuppressive treatment with MMF + corticosteroids,
- Inability to provide informed consent.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Germany14 sites
Kerckhoff-Klinik GmbH
Bad Nauheim
Charité - University Hospital Berlin
Berlin
University Hospital Essen
Essen
UHF- Universitäres Herz- und Gefässzentrum
Frankfurt, 60590
University Hospital Freiburg - Bad Krozingen
Freiburg im Breisgau
Universitätsmedizin Göttingen
Göttingen, 37035
University Hospital Greifswald
Greifswald
UKE Hamburg
Hamburg
University Hospital Heidelberg
Heidelberg
Universitäres Herzzentrum Lübeck
Lübeck, 23538
LMU Klinikum Standort Innenstadt
München, 80336
Klinikum rechts der Isar
Munich
LMU Klinikum
Munich
University Hospital Regensburg
Regensburg
About this study
Official 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.
Read the 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.
- Conditions
- Inflammatory Cardiomyopathy
- Being tested
- Mycophenolate Mofetil, Prednisolone, Mycophenolate Mofetil Placebo, Prednisolone Placebo
- Keywords
- inflammatory cardiomyopathy, heart failure, Mycophenolate mofetil, chronic myocarditis, myocarditis, enomyocardial biopsy, immunosupression
- Medical subject headings
- Heart Failure, Myocarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called MMF
Mycophenolate mofetil 1g bid for 6 months
PrednisoloneDrug
initially 1mg/kg in a step-down regime for 6 months
Mycophenolate Mofetil PlaceboDrug
Also called MMF Placebo
MMF matching Placebo
Prednisolone PlaceboDrug
Prednisolone matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Immunosuppressive treatment | Experimental | Mycophenolate mofetil (MMF) 1g bid and prednisolone at initially 1mg/kg in a step-down regime Receives: Drug: Mycophenolate Mofetil; Drug: Prednisolone |
| Placebo | Placebo comparator | Mycophenolate mofetil (MMF) and prednisolone Placebo Receives: Drug: Mycophenolate Mofetil Placebo; Drug: Prednisolone Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
Measured: 12 months follow-up
Secondary outcomes (15)
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
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 6 and 12 months follow-up
LVEF increase (echo)
Absolute increase in LVEF and rate of increase by ≥10% at 6 and 12 months follow-up (echo, metric, and binary).
Measured: 6 and 12 months follow-up
Ventricular remodelling (echo)
Decrease of left ventricular diameters and volumes by ≥10% at 6 and 12 months follow-up (echo).
Measured: 6 and 12 months follow-up
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).
Measured: 6 and 12 months follow-up
Diastolic parameters (echo)
Changes in diastolic parameters from baseline to 6 and 12 months follow-up (echo).
Measured: 6 and 12 months follow-up
Mitral and tricuspid regurgitation (echo)
Presence of MR/TR >2 at baseline and at 6 and 12 months followup (echo).
Measured: 6 and 12 months follow-up
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.
Measured: 6 and 12 months follow-up
NYHA
Changes in NYHA functional class from baseline to 6 and 12 months follow-up.
Measured: 6 and 12 months follow-up
QoL
Changes in patient-reported outcome (quality of life; QOL) from baseline to follow-up as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ).
Measured: 12 months
Cardiac autonomic function
Changes in cardiac autonomic function from baseline to 6 and 12 months follow-up.
Measured: 6 and 12 months follow-up
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.
Measured: 12 months
Biomarker
Time-averaged proportional change in NT-proBNP
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2022
- Study start28 Mar 2023
- Primary completion14 Apr 2025
- Study completion14 Apr 2025
Why it stopped: Premature end of recruitment due to lack of eligible patients. Within two years of recruitment only nine patients could be randomized out of 130 required patients as per trial protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Investigator-initiated, multicenter, randomized, double-blind, placebocontrolled clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- LMU Klinikum
- Sponsor type
- University, hospital or other
- Collaborators
- Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Technical University of Munich, Charite University, Berlin, Germany, University Hospital, Essen, University Hospital Erlangen, University Hospital Tuebingen
- Responsible party
- Principal investigator, Steffen Massberg, LMU Klinikum
- Investigators
- Steffen Massberg, Prof Dr. med., Principal investigator, LMU Klinikum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05570409
- Sponsor's protocol ID
- TRINITY
- Acronym
- TRINITY
- Status last verified
- Jul 2025
- First submitted
- 28 Sep 2022
- Last updated
- 25 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled TRial Evaluating Immunosuppressive Treatment in Patients With Chronic Virus-Negative Inflammatory cardiomyopaThY (TRINITY Trial)
- ClinicalTrials.gov ID
- NCT05570409
- Acronym / sponsor ID
- TRINITY / TRINITY
- Conditions
- Inflammatory Cardiomyopathy
- Keywords
- inflammatory cardiomyopathy, heart failure, Mycophenolate mofetil, chronic myocarditis, myocarditis, enomyocardial biopsy, immunosupression
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Premature end of recruitment due to lack of eligible patients. Within two years of recruitment only nine patients could be randomized out of 130 required patients as per trial protocol.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- LMU KlinikumUniversity, hospital or other
- Collaborators
- Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Technical University of Munich, Charite University, Berlin, Germany, University Hospital, Essen, University Hospital Erlangen, University Hospital Tuebingen
- Study start
- 28 Mar 2023 (actual)
- Primary completion
- 14 Apr 2025 (actual)
- Study completion
- 14 Apr 2025 (actual)
- First posted
- 6 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Investigator-initiated, multicenter, randomized, double-blind, placebocontrolled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Immunosuppressive treatment | Experimental | Drug: Mycophenolate Mofetil, Drug: PrednisoloneMycophenolate mofetil (MMF) 1g bid and prednisolone at initially 1mg/kg in a step-down regime |
| Placebo | Placebo comparator | Drug: Mycophenolate Mofetil Placebo, Drug: Prednisolone PlaceboMycophenolate mofetil (MMF) and prednisolone Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥18 years
- Medical therapy for HF for ≥3 months and <10 years according to current guideline recommendations
- Persistent reduction of LVEF <50% on a routine echocardiographic evaluation (Simpson's biplane) not older than 1 month at time of inclusion
- 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
- 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
Key exclusion criteria (7 listed)
- Histopathological (as approved by the histopathology core lab) and/ or clinical evidence of acute lymphocytic myocarditis, sarcoidosis, GCM or eosinophilic myocarditis,
- Known systemic inflammatory disease,
- Recent major surgery within <6 weeks, recent ICD implantation within <6 weeks or recent CRT implantation within <3 months prior to,
- Known coronary artery disease responsible for cardiac dysfunction (i.e., prior myocardial infarction, persistent stenosis ≥ 70%),
- Pregnancy or lactation,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate MofetilAlso: MMFMycophenolate mofetil 1g bid for 6 months | Drug | Immunosuppressive treatment |
| Prednisoloneinitially 1mg/kg in a step-down regime for 6 months | Drug | Immunosuppressive treatment |
| Mycophenolate Mofetil PlaceboAlso: MMF PlaceboMMF matching Placebo | Drug | Placebo |
| Prednisolone PlaceboPrednisolone matching placebo | Drug | Placebo |
Primary outcome
LVEF increase (metric)
Time frame: 12 months follow-up
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
LVEF increase (binary)
Time frame: 12 months follow-up
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).
15 secondary outcomes
Composite clinical outcome
Time frame: 12 months
LVEF increase 6 months (MRI)
Time frame: 6 months follow-up
Ventricular remodelling (MRI)
Time frame: 6 and 12 months follow-up
Strain (MRI)
Time frame: 6 and 12 months follow-up
LVEF increase (echo)
Time frame: 6 and 12 months follow-up
Ventricular remodelling (echo)
Time frame: 6 and 12 months follow-up
Strain (echo)
Time frame: 6 and 12 months follow-up
Diastolic parameters (echo)
Time frame: 6 and 12 months follow-up
Mitral and tricuspid regurgitation (echo)
Time frame: 6 and 12 months follow-up
Cardiopulmonary exercise capacity
Time frame: 6 and 12 months follow-up
NYHA
Time frame: 6 and 12 months follow-up
QoL
Time frame: 12 months
Cardiac autonomic function
Time frame: 6 and 12 months follow-up
Composite safety outcome
Time frame: 12 months
Biomarker
Time frame: 12 months
Results and safety
The study was stopped early (reason given: Premature end of recruitment due to lack of eligible patients. Within two years of recruitment only nine patients could be randomized out of 130 required patients as per trial protocol.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2025.
- study websiteLink provided by the sponsor.
- sponsor websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steffen Massberg, Prof Dr. med. principal investigator
LMU Klinikum
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Mycophenolate Mofetil and Prednisolone in people with Inflammatory Cardiomyopathy, run by LMU Klinikum at 14 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Premature end of recruitment due to lack of eligible patients. Within two years of recruitment only nine patients could be randomized out of 130 required patients as per trial protocol.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LVEF increase (metric) (time frame: 12 months follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2025.