Liver Transplantation, Chronic Renal Insufficiency
Conditions
Keywords
Renal impairment, Liver transplantation, Chronic Renal Insufficiency
Brief summary
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.
Interventions
20 mg basiliximab (Simulect) iv on day 0 and 4 after OLT
DRUGMyfortic
1080 mg q12 EC-MPS (Myfortic) po starting within 24h after OLT
DRUGeverolimus
1 mg q12 everolimus (Certican) po starting on 10th post-operative day
DRUGPrednisolone
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
Sponsors
Armin Goralczyk
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients undergoing primary liver transplantation. 2. Patients older than 18 years. 3. Patients with a hepatorenal syndrome. 4. Female patients of childbearing potential willing to perform a highly effective contraception during the study and 12 weeks after conclusion of study participation. 5. eGFR \< 50 ml/min at the time point of transplantation. 6. Serum creatinine levels \> 1.5 mg/dL at the time-point of transplantation.
Exclusion criteria
1. Patients with pre-transplant renal replacement therapy \> 14 days. 2. Patients with a reason for renal impairment other than a hepatorenal syndrome. 3. Patients with a known hypersensitivity to mTOR-inhibitors. 4. Patients with a known hypersensitivity to mycophenolate acid. 5. Patients with a known hypersensitivity to anti CD 25-monoclonal antibodies. 6. Patients with platelets \< 50.000/nl prior to initiation of therapy with mTOR inhibition. 7. Patients with triglycerides \> 350 mg/dl and cholesterol \> 300 mg/dl refractory to optimal medical treatment prior to initiation of therapy with mTOR inhibition. 8. Severe systemic infections and wound-healing disturbances. 9. Multiple organ graft recipients. 10. Patients with signs of a hepatic artery stenosis directly prior to initiation of therapy with everolimus. 11. Pregnant women will not be included in the study. 12. Patients with a psychological, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule. 13. Patients under guardianship (e.g., individuals who are not able to freely give their informed consent).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Steroid resistant rejection | 30 days |
Secondary
| Measure | Time frame |
|---|---|
| Liver function | 1 year |
| Calculated glomerular filtration rate | 1 year |
| Steroid resistant rejection | 1 year |
| Number of days on renal replacement therapy | 1 year |
| Graft survival | 1 year |
| Patient survival | 1 year |
Countries
Germany
Contacts
Primary ContactAiman Obed, Prof. Dr.
Backup ContactArmin D Goralczyk, MD
Outcome results
None listed