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

Phase 2

• Conditions: Liver Transplantation; Chronic Renal Insufficiency
• Interventions: Drug: Basiliximab (Simulect); Drug: Myfortic; Drug: everolimus; Drug: Prednisolone

• Registration Number: NCT00890253
• Lead Sponsor: Armin Goralczyk

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-04-28
• Study First Submitted QC: 2009-04-28
• Study First Posted: 2009-04-29
• Status Verified: 2010-01
• Study Start: 2010-01
• Last Update Submitted: 2011-09-14
• Last Update Posted: 2011-09-15
• Primary Completion: 2012-01
• Study Completion: 2013-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 29

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CNI-free Immunosuppression	Basiliximab (Simulect)	Immunosuppression after OLT including basiliximab, enteric-coated mycophenolate sodium (EC-MPS), and everolimus.
CNI-free Immunosuppression	Myfortic	Immunosuppression after OLT including basiliximab, enteric-coated mycophenolate sodium (EC-MPS), and everolimus.
CNI-free Immunosuppression	everolimus	Immunosuppression after OLT including basiliximab, enteric-coated mycophenolate sodium (EC-MPS), and everolimus.
CNI-free Immunosuppression	Prednisolone	Immunosuppression after OLT including basiliximab, enteric-coated mycophenolate sodium (EC-MPS), and everolimus.

Primary Outcome Measures

Name	Time	Method
Steroid resistant rejection	30 days

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University Medical Center Goettingen; 🇩🇪 Goettingen, Germany