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Everolimus bAsed caLcineurin inhibiTor frEe immunosuppRession oNe Year AfTer lIver transplantatiON (ALTERNATION)

ConditionsLiver AllograftLiver DiseasesLiver Transplantation
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-80
SponsorHannover Medical School

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Everolimus

    Drug

    Patients in the intervention group will be switched to CNI-free mTORI-based immunosuppression (EVR 3-8ng/ml) with MMF (250-750 mg bid)

  • Tacrolimus or Cyclosporine

    Drug

    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)

Treatment groups

150 Participants
are divided into 2 treatment groups
Group A: mTORI-based CNI-free ISExperimental treatment 1 intervention
Group B: Low dose CNI SOCActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

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

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

1

Rate of patients with elevated alanine aminotransferase (ALT)

Elevation of Alanine aminotransferase (ALT) \> 2x upper limit of normal (yes/no)

Time frame
38 months
2

Rate of patients with elevated aspartate aminotransferase (AST)

Elevation of aspartate aminotransferase (AST) \> 2x upper limit of normal (yes/no)

Time frame
38 months
3

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
4

Rate of patients with elevated gamma-glutamyltransferase (GGT)

Elevation of gamma-glutamyltransferase (GGT) \> 2x upper limit of normal (yes/no)

Time frame
38 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Hannover Medical School

Lead sponsor

Royal Infirmary of Edinburgh

Collaborator

Source ClinicalTrials.gov
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