CNI-free "Bottom"-up Immunosuppression in Patients Undergoing Liver Transplantation

• Status: Unknown status
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the trial is to evaluate efficacy and safety of delayed introduction (up to 30 days post-transplantation in patients without signs of acute rejection that had received an aIL-2 induction and MMF) of either cyclosporine or everolimus versus a 5-day delay of cyclosporine in combination with MMF.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Regensburg
• Collaborator: Novartis Pharmaceuticals
• Treatments: Cyclosporine; Cyclosporins; Everolimus; Sirolimus

Criteria

Inclusion Criteria:

1. Male and female liver transplant recipients of a primary liver transplant older than 18 years

2. Signed, written informed consent prior to randomization

3. MELD scores ≥25

4. Lack of relevant exclusion criteria

Exclusion Criteria:

1. Patients transplanted for autoimmune hepatitis

2. HIV positive patients

3. Patients with pre-transplant immunosuppressive treatment

4. Patients who are recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant.

5. Patients with renal failure or CKD/ESRD who require renal replacement therapy for more than 2 weeks prior to transplantation.

6. Patients with signs of hepatic artery thrombosis.

7. Patients with a hepatic encephalopathy grade of Stadium II, III and IV (somnolence, sopor and loss of consciousness

8. Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.

9. Patients who are recipients of ABO incompatible transplant grafts.

10. Patients with uncontrolled or therapy refractory hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L) at time of transplantation.

11. Patients with platelet count <50,000/mm3 at the time of randomization.

12. Patients with an absolute neutrophil count of <1,000/mm³ or white blood cell count of <2,000/mm³ at the time of randomization.

13. Patients with a creatinine/protein ratio indicating daily urinary protein excretion > 1 g/24h at time of randomization.

14. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS (1) they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m, or (2) have past 6 weeks from surgical bilateral oophorectomy with or without hysterectomy or (3) are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), copper coated IUD and double-barrier methods ( any double combination of male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the and for 3 months after study drug discontinuation.

15. Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation which would preclude liver biopsy after transplantation.

16. Patients with a psychologic, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule.

17. Patients under guardianship (e.g. individuals who are not able to freely give their informed consent).