CNI-free de Novo Protocol in Patients Undergoing Liver Transplantation With Renal Impairment

• Status: Completed
• Trial end date: 2012-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Background:

Patients undergoing liver transplantation with preexisting renal dysfunction are prone to further renal impairment with the early postoperative use of Calcineurin-inhibitors. However, there is only little scientific evidence for the safety and efficacy of de novo CNI free regimens in patients with impaired renal function undergoing liver transplantation. The objective of the study is to evaluate a de novo calcineurin-inhibitor-free immunosuppressive regimen based on induction therapy with anti-CD25 monoclonal anti- body, mycophenolate mofetil (MMF/MPA), and mTOR-inhibition to determine its safety and to investigate the preliminary efficacy in patients with impaired renal function at the time of liver transplantation. Methods/Design: Patients older than 18 years with renal impairment at the time of liver transplantation due to hepatorenal syndrome, eGFR < 50 ml/min and/or serum creatinine levels > 1.5 mg/dL will be included. Patients will receive a combination therapy with antiCD25-monoclonal antibodies, MMF, steroids and delayed sirolimus (day 10) and will be evaluated with regards to the incidence of steroid resistant acute rejection within the first 30 days after liver transplantation as the primary endpoint. The study is designed as prospective two-step trial requiring a maximum of 29 patients. In the first step 9 patients will be included. If 8 or more patients show no signs of biopsy proven steroid resistant rejection, additional 20 patients will be included. If in the second step a total of 27 or more patients reach the primary end-point the regimen is regarded to be safe and efficient. The follow up period will be one year after transplantation. The aim is to obtain safety and efficacy data for this new and innovative therapy regimen that might be the basis for a large prospective randomized multicenter trial in the future.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Regensburg
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion Criteria:

• Patients undergoing primary liver transplantation.

• Patients older than 18 years.

• Patients with a hepatorenal syndrome type I or II

• 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 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.

• 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 prior to inclusion.

• Multiple organ graft recipients.

• Patients with signs of a hepatic artery stenosis directly prior to initiation of therapy with Sirolimus.

• 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).