Clinical trial NCT00890253: Safety Study of Calcineurin-Inhibitor-Free Immunosuppression After Liver Transplantation
Official title: A Therapeutic Exploratory Study to Determine the Efficacy and Safety of Calcineurin-Inhibitor-Free De-novo Immunosuppression After Liver Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Liver Transplantation
Chronic Renal Insufficiency
Keywords: Renal impairment
Liver transplantation
Chronic Renal Insufficiency
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
First posted: 2009-04-29
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Steroid resistant rejection
timeFrame: 30 days
Secondary outcomes:
measure: Steroid resistant rejection
timeFrame: 1 year
measure: Liver function
timeFrame: 1 year
measure: Calculated glomerular filtration rate
timeFrame: 1 year
measure: Patient survival
timeFrame: 1 year
measure: Number of days on renal replacement therapy
timeFrame: 1 year
measure: Graft survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Goettingen
country: Germany
facility: University Medical Center Goettingen
Study officials:
affiliation: University Medical Center Goettingen
name: Aiman Obed, PD Dr.
role: STUDY_DIRECTOR
affiliation: University Medical Center Goettingen
name: Armin D Goralczyk, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goralczyk AD, Schnitzbauer A, Tsui TY, Ramadori G, Lorf T, Obed A. A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT. BMC Surg. 2010 Apr 9;10:15. doi: 10.1186/1471-2482-10-15.