A Phase 3 interventional study of Everolimus and Tacrolimus or Cyclosporine in Liver Allograft, Liver Diseases and Liver Transplantation, sponsored by Hannover Medical School. Recruiting at 16 sites in Germany. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-10-05.
Sponsored by Hannover Medical School · Phase 3, Interventional, and Treatment
The overall aim of this study is nephroprotection based on a calcineurin inhibitor (CNI)-free therapy beyond year one after orthotopic liver transplantation (OLT) in highly pre-selected patients with low rejection risk.
Randomized, prospective, multicenter, open-label, controlled trial in Liver allograft recipients beyond year one after transplantation (12-36 Months after liver transplantation) without graft dysfunction and with a surveillance biopsy without relevant subclinical graft injury.
The population of the trial will be adult LTR (≥18 and \< 80 years at the study entry) beyond the first year after OLT, who are eligible for a svLBx. The aim of this study is to compare two regimens of a reduced IS in the first year after OLT. Therefore, patients with an increased rejection risk have to be excluded by relevant liver enzyme elevation (ALT, and ALP > 2 ULN) and by a svLBx showing relevant graft injury guided by the BANFFmini criteria. These thresholds have been safely used by several studies with a complete IS withdrawal and should be safe for the proposed study which rather aims for a moderate reduction of IS. Within our single center program for biopsy guided personalized immunosuppression an extension of this strict BANFFmini criteria was safe in patients with immunosuppression minimization but no complete withdrawal.
LTR with a putative intolerance of the increased IS after a rejection provoked by the study intervention (steroid boli or higher CNI doses) like older patients, pregnant woman or patients with advanced kidney failure (eGFR \< 30 ml/min), ongoing infections or malignancies will also be excluded. We would not exclude per se LTR with autoimmune liver diseases as cause for OLT, because we did not observe any increased rejection risk in this patient population using a reduced IS with low dose CNI in our single center personalized IS program. Patients with an increased risk to be harmed by EVR, e.g. preexisting proteinuria, will be excluded as well. Screening of patients that are already on EVR/CNI combination therapy can be performed according to the judgement of participating centers. LTR on EVR/CNI because of reduced kidney function or because of recurrent viral infection, will not be harmed by the study, because both groups - intervention and SOC - will not lead to an increase in CNI dosage compared to the dosage before. Patients on EVR/CNI because of hepatocellular carcinoma: There is no prospective data showing an overall long-term survival benefit from a mTORI-based regimen and there is no prospective data showing a survival benefit between a mTORI containing regimen vs a low dose CNI regimen.
In contrast to previous studies on CNI-free mTORI-based IS, we will not focus exclusively on patients with a preexisting renal failure. Since we do not expect a relevantly increased rejection risk by the study intervention, the potential rejection risk has not to be balanced by a higher chance to benefit from renal protective IS as in previously performed trials. Therefore, it is ethically justifiable to include patients without significant renal impairment and thus to let them benefit from the possible benefit of the intervention.
The inclusion and exclusion criteria will select healthy LTR and more motivated patients that are willing to undergo a svLBx. However, the screening via a svLBx is essential considering the rate of BANFFmini in 30-40% of patients.
Patients in the intervention group will be switched to a mTORI-based immunosuppression (EVR 3-8ng/ml) with MMF (250-750 mg bid). CNI will be tapered stepwise in the 2 months lead-in phase.
Patients serving as control group need to fulfill the same inclusion criteria as the intervention group. Since they will also be eligible for minimization of IS guided by Banff criteria, after randomization IS will be provided based on a low dose CNI regime (Tac trough levels 2-4 ng/ml) with or without MMF (250 mg bid) as it is current standard of care. Patients, who have already been on low-dose CNI, will continue on their previous IS regime. According to recently published data showing reduced nephrotoxicity with a combined endpoint with new onset diabetes and new arterial hypertension with LCP-Tac Versus extended-released TAC, the preferred TAC in the study will be LCP-Tac. Only in case of intolerance, other tacrolimus preparations or CYS (trough level 50-80 ng/ml) should be used and discussion with the coordinating investigator may be advised.
In parallel for both study arms, a further minimization step to a low dose CNI therapy (control arm) or EVR low dose (trough level 3-6 ng/ml) both without MMF is advised after 14 months svLBx showing still no relevant graft injury.
824 studies on the registry are indexed under Liver Diseases; 152 are open to participants now.
This study's planned enrollment of 150 is above the median of 52 across 521 interventional studies indexed under Liver Diseases.
Browse Liver Diseases studies →Hannover Medical School is the lead sponsor of 202 studies on the registry; 25 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
*Women without defined as follows:
\< 50 years and in postmenopausal state > 1 year with serum FSH > 40 IU/l and serum estrogen \< 30 ng/l or a negative estrogen test, both at screening or
*Women of childbearing potential:
Exclusion Criteria:
Histological exclusion criteria in the baseline screening biopsy:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CNI-free IS with EVR (trough level 3-8 ng/ml) in combination with MMF (250-750 mg bid) with a second minimization step to EVR monotherapy depending on the 14 months (2 months lead in, 12 months full intervention) surveillance biopsy (svLbx)
Drug: Everolimus
Standard of care meaning IS with CNI (TAC trough level 2-4 ng/ml or CYS trough level 50-80 ng/ml) with or without low dose MMF (250 mg bid) with a second minimization step to CNI monotherapy (if not already performed) depending on the 14 months (2 months lead in, 12 months full intervention) svLbx
Drug: Tacrolimus or Cyclosporine
Patients in the intervention group will be switched to CNI-free mTORI-based immunosuppression (EVR 3-8ng/ml) with MMF (250-750 mg bid)
Also known as: mTORI
Patients in the comparator group will be switched to a low dose CNI therapy (TAC trough level 2-4 ng/ml; CYS trough level 50-80 ng/ml) with or without low dose MMF 250 mg bid)
Also known as: low dose CNI SOC
Change from baseline to 14 months in the eGFR between CNI-free and SOC group
The primary endpoint is change from baseline (CFB) to 14 months in the eGFR (ml/min) between the CNI-free and SOC group, where treatment effect is calculated by CFB-CNI-free minus CFB-SOC. The primary analysis will be performed in the Intention to Treat (ITT) population, i.e. all study subjects will be analyzed as randomized. The eGFR will be calculated using the new CKD-EPI Creatinine equation according to the national kidney foundation, 2021
Time frame: 14 months
Acute liver graft rejection or liver graft loss until month 14
Biopsy proven acute rejection (BPAR) (yes/no) is defined as liver enzyme elevation above 2x upper limit of normal (ULN) and histological criteria according to the most recent BANFF consensus
Time frame: 14 months
Change from baseline to 38 months in the eGFR
Change in estimated glomerular filtration rate (eGFR (ml/min)) from baseline to end of follow-up (38 months)
Time frame: 38 months
Acute liver graft rejection or liver graft loss until month 38
Biopsy proven acute rejection (BPAR) (yes/no) is defined as liver enzyme elevation above 2xULN and histological criteria according to the most recent BANFF consensus
Time frame: 38 months
Progression of chronic kidney disease
-Progression of chronic kidney disease to stage 4, 5 or requirement for renal replacement therapy (yes/no)
Time frame: 38 months
Liver-related mortality
-Incidence of liver-related mortality (yes/no)
Time frame: 38 months
-Progression of subclinical graft injury
Progression of subclinical graft injury (fibrosis) at rebiopsy at month 14, where progression in the svLBx is defined as reaching histological exclusion criteria from baseline biopsy (≥ 2 points)
Time frame: 14 months
-Progression of subclinical graft injury
Progression of subclinical graft injury (fibrosis) at rebiopsy at end of follow-up, where progression in the svLBx is defined as reaching histological exclusion criteria from baseline biopsy (≥ 2 points)
Time frame: 38 months
-Progression of subclinical inflammation
-Progression of subclinical inflammation at rebiopsy at month 14 (yes/no) where inflammation in the svLBx is defined as reaching exclusion criteria from baseline biopsy (≥ 2 points in any subscore)
Time frame: 14 months
-Progression of subclinical inflammation
-Progression of subclinical inflammation at rebiopsy at end of follow-up (yes/no) where inflammation in the svLBx is defined as reaching exclusion criteria from baseline biopsy (≥ 2 points in any subscore)
Time frame: 38 months
-Change in Quality of life measured with PROMIS
Quality of life measured as change from baseline to months 14
Time frame: 14 months
-Change in Quality of life measured with SF-36
Quality of life measured as change from baseline to months 14
Time frame: 14 months
-Change in Quality of life measured with PROMIS
Quality of life measured as change from baseline to end of follow-up
Time frame: 38 months
-Change in Quality of life measured with SF-36
Quality of life measured as change from baseline to end of follow-up
Time frame: 38 months
Donor Specific Antibodies
-De novo development of donor specific Human Leukocyte Antigen (HLA) antibodies (yes/no)
Time frame: 38 months
Liver Stiffness
-Increase in liver stiffness above 8,4 kilopascal (kPa) (yes/no)
Time frame: 38 months
Malignancy
-Incidence of malignancy (yes/no)
Time frame: 38 months
Infections
-Occurrence of infections requiring medical intervention or hospitalization (yes/no)
Time frame: 38 months
Comorbidities
-New onset of comorbidities including hypertension (yes/no), dyslipoproteinemia (yes/no) and diabetes mellitus (yes/no)
Time frame: 38 months
Rate of patients with elevated alanine aminotransferase (ALT)
Elevation of Alanine aminotransferase (ALT) \> 2x upper limit of normal (yes/no)
Time frame: 38 months
Rate of patients with elevated aspartate aminotransferase (AST)
Elevation of aspartate aminotransferase (AST) \> 2x upper limit of normal (yes/no)
Time frame: 38 months
Rate of patients with elevated alkaline phenyl phosphatase (ALP)
Elevation of alkaline phenyl phosphatase (ALP) \> 2x upper limit of normal (yes/no)
Time frame: 38 months
Rate of patients with elevated gamma-glutamyltransferase (GGT)
Elevation of gamma-glutamyltransferase (GGT) \> 2x upper limit of normal (yes/no)
Time frame: 38 months
Rate of patients with elevated international normalized ratio (INR)
Elevation of international normalized ratio (INR) \> 2x upper limit of normal (yes/no)
Time frame: 38 months
Adverse Events of Special Interest (AESI)
The following events should be reported as AESI: Allograft dysfunction; Steroid-resistant rejection, defined as rejection requiring, at the discretion of the local principal investigators, an additional course of high-dose corticosteroids or treatment with antithymocyte globulin/thymoglobulin or a comparable lymphocyte-depleting therapy; Chronic rejection as defined by Banff Foundation; Increase ≥2 points in any Liver Allograft Fibrosis (LAF) component in any follow up liver biopsy in central pathology report; Reaching the exclusion criteria in the central pathology report in any follow up liver biopsy
Time frame: 38 months
Started Aug 2026 (actual). Primary completion is estimated for Jun 2029, 34 months after the start.
Of 19 phase 3 interventional studies under Liver Diseases, half reached primary completion within 54 months of starting (the median), counting those still running; a quarter within 37 and three quarters within 70. This study's planned 34 months is below that.
Start moved once since we started tracking on Sep 25, 2026: Jun 2026 → Aug 2026, on Oct 5, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Everolimus