Conversion to Everolimus From Calcineurin Inhibitor With Mycophenolic Acid: Impact on Long Term Renal Function in Liver Transplantation.

• Status: Completed
• Trial end date: 2019-07-31
• Target enrollment: 0
• Participant gender: All

Summary

This study will examine the renal sparing impact of implementing a strategy of conversion to everolimus from a calcineurin inhibitor based immunosuppressive protocol at 3 months post liver transplant

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Milton S. Hershey Medical Center
• Collaborator: Novartis Pharmaceuticals
• Treatments: Calcineurin Inhibitors; Cyclosporine; Cyclosporins; Everolimus; Mycophenolate mofetil; Mycophenolic Acid; Sirolimus; Tacrolimus

Criteria

Inclusion Criteria:

• Ability and willingness to provide written informed consent and adhere to study regimen.

• Primary deceased donor liver transplant recipients 18-70 years of age

• Functioning allograft at randomization (AST, ALT, Total Bilirubin levels ≤3 times ULN, and AlkP and GGT levels ≤ 5 times ULN). Elevated GGT alone, in combination with AST, ALT, total bilirubin and AlkP within defined range does not exclude patients from randomization.

• Recipients on an immunosuppressive regimen of corticosteroids and tacrolimus.

• Confirmed recipient HCV status at Screening (either by serology or PCR).

• Abbreviated MDRD eGFR ≥ 30 mL/min/1.73m2. Local and central serum creatinine results within 5 days prior to randomization, however no sooner than Day 25 post-transplantation.

• Verification of at least one tacrolimus trough level of ≥ 8 ng/mL one week prior to randomization. Target trough levels above 8 ng/mL prior to randomization.

• Patients able to take oral medication at time of randomization.

Exclusion Criteria:

• Recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant. Combined liver kidney transplant recipients.

• Living donor or split liver recipients.

• History of malignancy of any organ system within past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin or HCC.

• Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3 nodules all < 3 cm, per explant histology of recipient liver.

• Use of antibody induction therapy.

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

• Recipients of ABO incompatible transplant grafts.

• Recipients of Hepatitis B surface antigen or HIV donor organs.

• Surgical or medical condition, which might significantly alter absorption, distribution, metabolism and excretion of study drug.

• Women of child-bearing potential (WOCBP): 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 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 and for 3 months after study drug discontinuation.

• History of coagulopathy or medical condition requiring long-term anticoagulation which would preclude liver biopsy after transplantation. (Low dose aspirin treatment or interruption of chronic anticoagulant is allowed).

Enrollment Exclusion - Randomization

• Severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L) within 6 months of transplantation. Controlled hyperlipidemia is acceptable at time of randomization.

• Platelet count < 50,000/mm3 at randomization.

• Absolute neutrophil count < 1,000/mm³ or white blood cell count <2,000/mm³ at randomization.

• Patients positive for HIV: Negative laboratory results within 6 months before randomization are acceptable.

• Clinically significant systemic infection requiring IV antibiotics at randomization. Patients in a critical care setting at randomization requiring life support measures such as mechanical ventilation, dialysis, or vasopressor agents.

• Patients on renal replacement therapy within 7 days prior to randomization.

• Thrombosis of major hepatic arteries, major hepatic veins, portal vein and inferior vena cava. Results obtained within 5 days prior to randomization are acceptable, however no sooner than Day 25 post-transplantation.

• Acute rejection requiring antibody therapy or more than one steroid sensitive episode of acute rejection during the run-in period. Includes patients who have not completed steroid treatment for acute rejection within 7 days prior to randomization.