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.
Inclusion Criteria:
Men**, women*, inter/diverse aged ≥ 18 or <80 years
Signed written informed consent from subject
Liver allograft recipients, either deceased or living donor liver transplant
Liver transplantation more than 12 months ago and less than 36 months ago
Recipients of single organ transplant only
LTR on CNI-based maintenance IS
Liver enzymes: ALT < 2x ULN and ALP< 2 ULN
*Women without childbearing potential defined as follows:
at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or
hysterectomy or uterine agenesis or
≥ 50 years and in postmenopausal state > 1 year or
< 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:
who are practicing sexual abstinence (periodic abstinence and withdrawal are not acceptable) or
who have sexual relationships with female partners only and/or with sterile male partners or
who are sexually active with fertile male partner, have two negative pregnancy tests with a sensitivity of at least 25 mIU/ml during screening (it is recommended that the second test be performed 8-10 days after the first test) and agree to use at least one highly *** from the time of screening until 8 weeks after completion of treatment (or even 90 days for males if MMF has been taken previously). Preferably, two complementary forms of contraception should be used simultaneously. Pregnancy tests should be repeated if clinically indicated (e.g. after a contraceptive failure has been reported).
Exclusion Criteria:
Previous CNI-free IS
Acute or chronic rejection within the 36 months prior to screening
Prednisolone intake due to another autoimmune disease for more than 8 weeks
eGFR <30ml/min and/or proteinuria >0.5g/l (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI might be required and proteinuria as a contraindication for mTORI-based therapy)
Need for chronic anti-coagulation that cannot be safely discontinued to perform a liver biopsy
Inability to participate in frequent monitoring of liver function (every 8 weeks) and clinical visits during the trial duration (38 months)
Malignancy or active infection including active, replicative viral hepatitis (chronic hepatitis does not belong to exclusion criteria)
Recurrence of underlying liver disease
Subjects who are pregnant or breastfeeding
Hypersensitivity or intolerance to any of the components of the medications used
Participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior enrolment or within five half-lives of the Investigational Medicinal Product (IMP), whichever is longer)
Any medical condition which could compromise participation in the study according to the investigator's assessment.
Accommodation in an institution pursuant to a court or administrative order
Histological exclusion criteria in the baseline screening biopsy:
heinrich.sophia@mh-hannover.de+49-511-532 ext. 6619
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)
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
grahl.esther@mh-hannover.de+49-176-1 532-7247
Heidelberg, Baden-Wurttemberg 69120, Germany
Tübingen, Baden-Wurttemberg 72076, Germany
Würzburg, Bavaria 97080, Germany
Hamburg, Free and Hanseatic City of Hamburg 20246, Germany
Hanover, Lower Saxony 30625, Germany
Rostock, Mecklenburg-Vorpommern 18057, Germany
Aachen, North Rhine-Westphalia 52074, Germany
Bonn, North Rhine-Westphalia 53105, Germany
Essen, North Rhine-Westphalia 45147, Germany
Münster, North Rhine-Westphalia 48149, Germany
Mainz, Rhineland-Palatinate 55131, Germany
Magdeburg, Saxony-Anhalt 39120, Germany
Kiel, Schleswig-Holstein 24105, Germany
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