Everolimus-Based Calcineurin-Inhibitor-Free Immunosuppression with Drug Combination in Patients One Year After Liver Transplantation

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What is this study about?

The study involves people who have had a liver transplantation at least one year ago. After a transplant, patients need medicines to keep the new liver working and to protect other organs, especially the kidneys. The trial tests a new approach that uses everolimus together with other medicines but avoids drugs known as calcineurin inhibitors such as tacrolimus or cyclosporin. In the standard group, patients continue the usual regimen that includes those calcineurin inhibitors, often combined with mycophenolate mofetil.

The purpose of the study is to determine whether the calcineurin‑inhibitor‑free regimen can better preserve kidney function compared with the standard treatment. Participants will be randomly assigned to one of the two groups and will take the assigned medicines for about a year, with regular clinic visits, blood tests, and occasional imaging. Kidney health will be checked using a blood test called estimated glomerular filtration rate, which estimates how well the kidneys filter waste.

Throughout the trial, doctors will also look for signs that the transplanted liver is still healthy by performing a small tissue sample test called a biopsy and by monitoring for any serious problems such as rejection, infection, or the development of chronic kidney disease. Quality of life will be assessed with questionnaires, and any new health issues, including high blood pressure or diabetes, will be recorded. The study will continue follow‑up for several years to see long‑term effects.

1 randomization into treatment group

after enrollment, the patient is assigned by the study to one of two treatment groups using a random process.

2 baseline assessments

the patient undergoes initial evaluations that include blood tests to measure kidney function, a liver biopsy to assess graft condition, and completion of quality‑of‑life questionnaires.

3 initiation of medication regimen

if assigned to the everolimus‑based arm, the patient starts oral everolimus 2 mg once daily together with oral mycophenolate mofetil 1500 mg daily.

if assigned to the standard calcineurin‑inhibitor arm, the patient starts either oral tacrolimus 0.13 mg per kilogram of body weight daily or oral ciclosporin 12 mg per kilogram of body weight daily, according to the investigator’s choice.

4 daily medication intake

the patient takes the prescribed medication(s) by mouth each day at the same time, following the dosage instructions provided.

5 regular study visits for monitoring

the patient attends scheduled clinic visits at approximately month 1, month 3, month 6, month 12, month 14, month 24, and month 38 after randomization.

each visit includes a review of medication adherence, measurement of blood pressure, and collection of blood samples.

6 kidney function testing

at every study visit, the patient has a kidney function test (estimated glomerular filtration rate, eGFR) performed to track changes over time.

7 liver biopsy procedures

the patient undergoes a repeat liver biopsy at month 14 and again at month 38 to evaluate graft health.

8 quality‑of‑life questionnaires

the patient completes standardized quality‑of‑life questionnaires at month 14 and month 38 to assess overall well‑being.

9 continuation of medication

the prescribed medication(s) are continued for the duration of the trial, up to month 38, unless the investigator decides to stop treatment because of safety concerns.

10 final assessment

at month 38, the patient undergoes the final study procedures, including blood tests, a liver biopsy, and completion of the quality‑of‑life questionnaire, after which the trial participation ends.

Who Can Join the Study?

Be a man or woman who is at least 18 years old but younger than 80 years.
If you are a woman who could become pregnant, you must have a negative pregnancy test and agree to use a reliable method of birth control (such as hormonal contraception plus a condom) from the screening visit until 8 weeks after the study ends; women who cannot become pregnant (for example after removal of the uterus or ovaries, after menopause, or age 50+ with menopause) do not need birth control.
If you are a man who can father children, you must use a condom while taking the study medication and for at least 90 days after stopping it; if your partner could become pregnant, she must also use reliable birth control.
Sign a written informed consent form agreeing to take part in the study.
Have received a liver transplant (from a deceased or living donor).
Your transplant must have been performed more than 12 months ago but less than 36 months ago.
Have received only a single organ transplant (no other organ transplants).
Currently be on a maintenance regimen that includes a calcineurin inhibitor (a type of medication that suppresses the immune system to prevent organ rejection).
Your liver enzyme levels must be within safe limits: alanine aminotransferase (ALT) and alkaline phosphatase (ALP) must each be less than twice the upper normal range.

Who Cannot Join the Study?

Having already used a calcineurin‑inhibitor‑free immunosuppression (CNI‑free IS) regimen before the study.
Needing long‑term anticoagulation (blood‑thinning medication) that cannot be safely stopped to allow a liver biopsy.
Being unable to attend regular check‑ups of liver function every 8 weeks and clinic visits for the 38‑month study period.
Having cancer (malignancy) or an active infection, including a virus that is actively replicating in the liver (such as active viral hepatitis).
Experiencing a return of the original liver disease that led to the transplant.
Being currently pregnant or breastfeeding.
Using any medication that the study lists as prohibited, unless it can be safely switched to another drug at least five drug half‑lives before the study starts (the time it takes for half of the drug to leave the body).
Having an allergy or intolerance to any of the medicines that will be used in the trial.
Being enrolled in another clinical trial or having taken other investigational drugs or devices within the past 30 days or within five drug half‑lives, whichever is longer.
Having any other medical problem that the investigator believes could make participation unsafe.
Living in a facility because of a court or administrative order.
Showing certain findings on the initial liver biopsy, such as:
- More than mild inflammation in the liver tissue (portal tract inflammation, interface hepatitis, or lobular inflammation).
- Inflammation of the bile ducts or small blood vessels (biliary inflammation, endothelialitis, portal microvasculitis, central perivenulitis).
- Advanced scarring (fibrosis) at stage 2 or higher on any fibrosis scoring system.
- Evidence of the body rejecting the transplanted liver (acute or chronic rejection, including T‑cell‑mediated, antibody‑mediated, plasma‑cell‑rich, or chronic duct‑openic rejection).
Having had an episode of acute or chronic rejection of the liver transplant within the 36 months before screening.
Taking prednisolone (a steroid medication) for another autoimmune disease for more than 8 weeks.
Having an estimated kidney function (eGFR) lower than 30 ml/min and/or urine protein loss greater than 0.5 g/L (proteinuria), which could increase the risk of kidney problems.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
University Hospital Jena KöR	Jena	Germany
Medizinische Hochschule Hannover	Hanover	Germany
Center For Pediatric And Adolescent Medicine Of The Johannes Gutenberg University Mainz	Mainz	Germany
Rostock University Medical Center	Rostock	Germany

Other Sites

Site Name	City	Country
Otto Von Guericke Universitaet Magdeburg	Magdeburg	Germany
Rheinische Friedrich-Wilhelms-Universitaet Bonn	Bonn	Germany
Celjzjc Ueguzmtcilmnhxoqzpqv Bxhjln Ksq	Berlin	Germany
Ulcrsjlhpmybmbgzlrtql Ekzlp Asa	Essen	Germany
Uxawztntai Mwvqfqj Ctzvpa Hklfdkedgfnvtafij	Hamburg	Germany
Umguzgqrexuzriqlotvgo Tufjabxye Arr	Tuebingen	Germany
Uihysilacubykhmvjkzpa Mpxccgvg Ank	Munster	Germany
Uvimoyudysdmsunwhhpyr Wxorrdzfu Ang	Wuerzburg	Germany
Uvhhdypczpoutdyxrdfzb Hxejbocgpj Abb	Heidelberg	Germany
Ustwwhaxiovpivejcwfal Skbxmintdhwstljmmo Ava	Kiel	Germany
Usjbtqqpuiyifwrlbyfki Adqcii Aiv	Aachen	Germany
Ufoionzwtsaaeczawimzo Rrgxgnjkdf Aqd	Regensburg	Germany

Trial status

Country	Status	Recruitment Start
Germany	Recruiting	15.06.2026

Trial locations

Investigated Drugs:

Everolimus is a medication that works by blocking a pathway in immune cells, helping to prevent the body from attacking a new liver. In this study it is used instead of the usual drugs that can harm the kidneys, with the goal of protecting kidney function while still stopping rejection of the transplanted liver.

Tacrolimus is a commonly used drug that suppresses the immune system by inhibiting a protein called calcineurin. It is part of the standard treatment for liver transplant patients and helps keep the new liver from being rejected, but it can sometimes reduce kidney function over time.

Ciclosporin is another calcineurin‑inhibiting medicine that is often used to prevent rejection after a liver transplant. Like tacrolimus, it is effective at controlling the immune response but may also have side effects that affect the kidneys.

Mycophenolate mofetil is an immune‑modulating drug that works by stopping certain immune cells from multiplying. It is given together with other medicines in the trial to provide additional protection against liver rejection while allowing the researchers to test whether reducing calcineurin‑inhibitor use can improve kidney health.

Investigated Diseases:

Liver transplant

Acute liver graft rejection – This is a sudden immune response where the body attacks the transplanted liver. It typically appears weeks to months after the transplant. Liver enzymes rise, indicating damage. If the response continues, the transplanted tissue can become scarred. Over time, the liver may lose its ability to function properly.

Chronic kidney disease – This condition involves a gradual loss of kidney function over years. It often starts with mild reductions in filtering ability. As it progresses, waste products build up in the blood. The disease is staged, with higher stages indicating more severe loss. Eventually, kidney function may become very low.

Hypertension – High blood pressure means the force of blood against artery walls is consistently elevated. It can develop slowly without obvious symptoms. Over time, the arteries may become stiffer. The heart works harder to pump blood. Persistent high pressure can affect many organs.

Dyslipidemia – This disorder refers to abnormal levels of fats in the blood, such as cholesterol or triglycerides. It often develops gradually due to diet, genetics, or lifestyle. Elevated blood fats can deposit in blood vessel walls. The buildup may narrow the vessels. The condition can worsen if not managed.

Diabetes mellitus – Diabetes is a chronic condition where the body cannot properly control blood sugar levels. It may develop gradually and often has few early signs. High blood sugar can affect nerves, blood vessels, and organs. The disease can become more difficult to control over time. Ongoing high sugar levels can lead to further complications.

Malignancy – Malignancy means the presence of cancerous cells that grow uncontrollably. It can start as a small cluster of abnormal cells. Over months to years, the cells may multiply and spread. The growth can invade surrounding tissues. The disease may become more extensive if it continues.

Infection – An infection occurs when microorganisms such as bacteria, viruses, or fungi invade the body. It can begin with mild symptoms and spread if not cleared. The invading organisms multiply, causing inflammation. The body’s response may increase over days to weeks. Repeated or severe infections can affect overall health.

Liver graft fibrosis – Fibrosis is the formation of scar tissue within the transplanted liver. It usually develops slowly as normal tissue is replaced by scar. The scar tissue can stiffen the liver. Over time, more of the liver may become fibrotic. This can limit the liver’s ability to work efficiently.

Liver graft inflammation – Inflammation is the immune system’s reaction to perceived injury in the transplanted liver. It may start with mild swelling and progress to larger areas of irritation. Persistent inflammation can cause damage to liver cells. The affected area can enlarge over weeks to months. Continued inflammation can impair liver function.

Trial ID:

2025-524312-11-00

Protocol code:

ALTERNATION

Trial Phase:

Therapeutic confirmatory (Phase III)

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Everolimus-Based Calcineurin-Inhibitor-Free Immunosuppression with Drug Combination in Patients One Year After Liver Transplantation

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?