A 24 month, multi-center, open-label, randomized, controlled study to evaluate the efficacy and safety of concentration controlled everolimus to eliminate or to reduce tacrolimus compared to tacrolimus in de novo liver transplant recipients.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 690

Inclusion Criteria

•Ability and willingness to provide written informed consent and adhere to study regimen.
•Recipients who are 18-70 years of age of a primary liver transplant from a deceased donor.
•Recipients who have been initiated on an immunosuppressive regimen that contains corticosteroids and tacrolimus, 3-7 days post-transplantation.
•Confirmed recipient HCV status at Screening (either by antibody or by PCR).
•Allograft is functioning at an acceptable level by the time of randomization as defined by AST, ALT, Total Bilirubin levels =3 times ULN and AlkP and GGT = 5 times ULN.
•Abbreviated MDRD eGFR = 30 mL/min/1.73m2. Results obtained within 5 days prior to randomization are acceptable, however no sooner than Day 25 post-transplantation.
•Verification of at least one tacrolimus trough level of = 8 ng/mL in the week prior to randomization. Investigators should make adjustments in tacrolimus dosing to continue to target trough levels above 8 ng/mL prior to randomization.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Patients who are recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant. Patients who have a combined liver-kidney transplant.
•Recipients of a liver from a living donor, or of a split liver.
•History of malignancy of any organ system within the 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 (see next criteria).
•Hepatocellular carcinoma that does not fulfill Milan criteria at the time of transplantation as per explant histology of the recipient liver.
•Any use of antibody induction therapy.
•Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients
•Patients who are recipients of ABO incompatible transplant grafts.
•Recipients of organs from donors who test positive for Hepatitis B surface antigen or HIV are excluded.
•Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study drug.
•Patients with any 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).

•Patients who have a spot urine protein/creatinine ratio that indicates = 1.0 g/24 hrs of proteinuria at baseline.
•Use of immunosuppressive agents or treatments after baseline that are not utilized in the protocol.

•Patients who have severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L) within 6 months of transplantation. Patients with controlled hyperlipidemia are acceptable at the time of randomization.
•Patients with platelet count < 50,000/mm3 at the time of randomization.
•Patients with an absolute neutrophil count of < 1,000/mm³ or white blood cell count of < 2,000/mm³ at the time of randomization.
•Patients who are unable to take oral medication at time of randomization.
•Patients who have tested positive for HIV. Negative laboratory results obtained within 6 months prior to randomization are acceptable.
•Patients with clinically significant systemic infection requiring active use of IV antibiotics at the time of randomization.
•Patients who are in a critical care setting at the time of randomization requiring life support measures such as mechanical ventilation, dialysis, requirement of vasopressor agents.
•Patients who require renal replacement therapy for clearance within 7 days prior to randomization.
•The presence of thrombosis via Doppler ultrasound of the 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.
•An episode of acute rejection that required antibody therapy or more than one steroid-sensitive episode of acute rejection during the run-in period. This includes patients who have not completed steroid treatment for acute rejection within 7 days prior to randomization.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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