Safety Study of Calcineurin-Inhibitor-Free Immunosuppression After Liver Transplantation

Study Overview
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Brief Summary
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A prospective, non-randomized two stage monocentric phase II clinical trial to evaluate a de-novo calcineurin-inhibitor (CNI)-free immunosuppressive regimen based on induction therapy with anti-CD25 monoclonal anti-body (basiliximab), mycophenolic acid (MPA), and mammalian target of rapamycin (mTOR) - inhibition with everolimus to determine its safety and to investigate the preliminary efficacy in patients with impaired renal function at the time-point of liver transplantation (OLT) with regards to the incidence of steroid resistant acute rejection within the first 30 days after liver transplantation.

Official Title
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A Therapeutic Exploratory Study to Determine the Efficacy and Safety of Calcineurin-Inhibitor-Free De-novo Immunosuppression After Liver Transplantation

Conditions
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Liver Transplantation, Chronic Renal Insufficiency

Intervention / Treatment
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* Drug: Basiliximab (Simulect)
* Drug: Myfortic
* Drug: everolimus
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing primary liver transplantation. Patients older than 18 years. Patients with a hepatorenal syndrome. Female patients of childbearing potential willing to perform a highly effective contraception during the study and 12 weeks after conclusion of study participation. eGFR < 50 ml/min at the time point of transplantation. Serum creatinine levels > 1.5 mg/dL at the time-point of transplantation. Exclusion Criteria: Patients with pre-transplant renal replacement therapy > 14 days. Patients with a reason for renal impairment other than a hepatorenal syndrome. Patients with a known hypersensitivity to mTOR-inhibitors. Patients with a known hypersensitivity to mycophenolate acid. Patients with a known hypersensitivity to anti CD 25-monoclonal antibodies. Patients with platelets < 50.000/nl prior to initiation of therapy with mTOR inhibition. Patients with triglycerides > 350 mg/dl and cholesterol > 300 mg/dl refractory to optimal medical treatment prior to initiation of therapy with mTOR inhibition. Severe systemic infections and wound-healing disturbances. Multiple organ graft recipients. Patients with signs of a hepatic artery stenosis directly prior to initiation of therapy with everolimus. Pregnant women will not be included in the study. Patients with a psychological, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule. Patients under guardianship (e.g., individuals who are not able to freely give their informed consent).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNI-free Immunosuppression<br>Immunosuppression after OLT including basiliximab, enteric-coated mycophenolate sodium (EC-MPS), and everolimus. | Drug: Basiliximab (Simulect)<br>* 20 mg basiliximab (Simulect) iv on day 0 and 4 after OLT<br>* Other names: Basiliximab: Simulect;Drug: Myfortic<br>* 1080 mg q12 EC-MPS (Myfortic) po starting within 24h after OLT<br>* Other names: Enteric-coated mycophenolate sodium: EC-MPS, Myfortic;Drug: everolimus<br>* 1 mg q12 everolimus (Certican) po starting on 10th post-operative day<br>* Other names: Certican;Drug: Prednisolone<br>* Prednisolone 1mg per kg body weight starting within 24 hours after transplantation. Then q24 but with reduction by 5 mg every 48 hours until maintenance dose of 7.5 mg<br>* Other names: Prednisone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steroid resistant rejection |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steroid resistant rejection |  | 1 year | 
| Liver function |  | 1 year | 
| Calculated glomerular filtration rate |  | 1 year | 
| Patient survival |  | 1 year | 
| Number of days on renal replacement therapy |  | 1 year | 
| Graft survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal impairment, Liver transplantation, Chronic Renal Insufficiency