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.
- Conditions
- liver transplantation
- Registration Number
- EUCTR2007-001821-85-GB
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
• 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.
• Allograft is functioning at an acceptable level by the time of randomization as defined by the 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 the defined range does not exclude patients from randomization.
• 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 serology or by PCR).
• Abbreviated MDRD eGFR = 30 mL/min/1.73m2. Local and central serum creatinine
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.
• Patients who are able to take oral medication at time of 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
•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.
•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 bemaintained throughout the and for 3 months after study drug discontinuation.
•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 with a confirmed spot urine protein/creatinine ratio that indicates = 1.0 g/24 hrs of proteinuria at baseline and that cannot be explained by immediate post operative effects.
•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
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