Efficacy and Safety of Everolimus in Liver Transplant Recipients of Living Donor Liver Transplants
- Conditions
- iver Transplantation
- Registration Number
- JPRN-jRCT2080222301
- Lead Sponsor
- ovartis Pharma K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 280
-Written informed consent
-Subject aged more than or equal to 18 years of a primary, orthotopic liver allograft, from a living donor
-Subject negative for HIV
Inclusion criteria at Randomization:
-Subject was initiated on tacrolimus-based immunosuppressive regimen with steroids and other immunosuppression
Long term extension for patients in Japan:
-Written informed consent must be obtained before any extension specific assessment is performed.
-Ability and willingness to adhere to study regimen.
-Completed Month 24 visit of core study and continuously being treated with assigned regimen.
-Subjects transplanted for acute liver failure
-HCV negativesubjects receiving a transplant from HCV positive donor
-Subjects receiving multiple solid organ (including multiple liver lobes/segments) or islet cell tissue transplants, or have previously received an organ or tissue transplant.
-Subjects receiving an ABO incompatible allograft.
-MELD-score more than 35 within 1 month prior to transplantation.
-Use of immunosuppressive or antibody induction agents not specified in the protocol.
-History of malignancy of any organ system (except hepatocellular carcinoma or localized basal cell carcinoma of the skin)
-Hepatocellular carcinoma with extrahepatic spread or macrovascular invasion
-Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
-Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 2 weeks of the last dose of study medication
-History of hypersensitivity to any of the study drugs or to drugs with similar chemical class, or to any of the excipients
Exclusion criteria at Randomization:
-Any post-transplant history of thrombosis, occlusion or stent placement in any major hepatic artery, major/reconstructed hepatic vein, portal vein or inferior vena cava at any time during the run-in period prior to randomization.
-Subjects with a confirmed spot urine protein/creatinine ratio that indicates more than or equal to 1.0 g/24 hrs of proteinuria
-Subjects who have severe hypercholesterolemia (more than 350 mg/dL; more than 9 mmol/L) or hypertriglyceridemia (more than 500 mg/dL; more than 8.5 mmol/L) at randomization.
-Subjects with platelet count less than 30,000/mm3.
-Subjects with an absolute neutrophil count of less than 1,000/mm3 or white blood cell count of less than 2,000/mm3.
-Subjects with systemic infection requiring active use of IV antibiotics.
-Subjects requiring life support measures such as ventilation, dialysis, vasopressor agents.
-Subjects who require renal replacement therapy within 7 days prior to randomization.
-Subjects with detectable HBV DNA at time of randomization
-Subjects meeting the following criteria for acute rejection during the run in period:
-Any acute rejection in the week prior to randomization.
-2 treated acute rejections.
-Any rejection requiring antibody treatment.
-Any severe cellular (and/or any humoral) rejection. Other protocol-defined inclusion/exclusion criteria may apply.
Long term extension for patients in Japan:
-Use of medication that is prohibited by the study protocol at Month 24.
-Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
-History of hypersensitivity to any of the study drugs or to drugs with similar chemical class, or to any of the excipients
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>Composite efficacy failure of treated biopsy proven acute rejection, graft loss or death in everolimus with reduced tacrolimus group compared to standard tacrolimus [ Time Frame: at 12 months post transplantation ] <br><br>Rate of composite efficacy failure of treated biopsy proven acute rejection (tBPAR more than or equal to RAI score 3), graft loss (GL) or death (D) in everolimus with reduced tacrolimus group compared to standard tacrolimus at 12 months
- Secondary Outcome Measures
Name Time Method