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

NCT ID: NCT00890253

Last Updated: 2011-09-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-01-31

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.

Conditions

Liver Transplantation; Chronic Renal Insufficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CNI-free Immunosuppression

Immunosuppression after OLT including basiliximab, enteric-coated mycophenolate sodium (EC-MPS), and everolimus.

Group Type: EXPERIMENTAL

Basiliximab (Simulect)

Intervention Type: DRUG

20 mg basiliximab (Simulect) iv on day 0 and 4 after OLT

Myfortic

Intervention Type: DRUG

1080 mg q12 EC-MPS (Myfortic) po starting within 24h after OLT

everolimus

Intervention Type: DRUG

1 mg q12 everolimus (Certican) po starting on 10th post-operative day

Prednisolone

Intervention Type: DRUG

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

Interventions

Basiliximab (Simulect)

20 mg basiliximab (Simulect) iv on day 0 and 4 after OLT

Intervention Type: DRUG

Myfortic

1080 mg q12 EC-MPS (Myfortic) po starting within 24h after OLT

Intervention Type: DRUG

everolimus

1 mg q12 everolimus (Certican) po starting on 10th post-operative day

Intervention Type: DRUG

Prednisolone

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

Intervention Type: DRUG

Other Intervention Names

Basiliximab: Simulect; Enteric-coated mycophenolate sodium: EC-MPS, Myfortic; Certican; Prednisone

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Armin Goralczyk

OTHER

Sponsor Role: lead

Responsible Party

Armin Goralczyk

Dr.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Aiman Obed, PD Dr.

Role: STUDY_DIRECTOR

University Medical Center Goettingen

Armin D Goralczyk, Dr.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Goettingen

Locations

University Medical Center Goettingen

Göttingen, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Aiman Obed, Prof. Dr.

Role: CONTACT

aobed@chirurgie-goettingen.de

+49 551 3912296

Armin D Goralczyk, MD

Role: CONTACT

agoralczyk@med.uni-goettingen.de

+49 551 3914638

Facility Contacts

Armin D Goralczyk, Dr.

Role: primary

agoralczyk@med.uni-goettingen.de

+49 551 398490

Aiman Obed, PD Dr.

Role: backup

aobed@chirurgie-goettingen.de

+49 551 39 12296

References

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.

Reference Type: DERIVED

PMID: 20380712 (View on PubMed)

Other Identifiers

CILT08

Identifier Type: -

Identifier Source: org_study_id