Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients

• Status: Completed
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This trial was designed to address important issues that impact recipients of liver allografts as well as clinicians, ie, renal function, reduction or discontinuation of tacrolimus early post-transplantation, and progression rate of fibrosis in hepatitis C virus (HCV) positive patients.

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

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Everolimus; Sirolimus; Tacrolimus

Criteria

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 hepatitis C virus (HCV) status at Screening (either by antibody or by PCR (polymerase chain reaction).

• Allograft is functioning at an acceptable level by the time of randomization as defined by protocol specific laboratory values.

• Abbreviated Modification of Diet in Renal Disease estimated glomerular filtration rate (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 1 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.

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 (hepatocellular carcinoma) (see next criteria).

• Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3 nodules all < 3 cm) 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.

• Women of child-bearing potential (WOCBP).

• 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).

Other protocol-defined inclusion/exclusion criteria may apply.