Everolimus Post Orthotopic Liver Transplant

• Status: Unknown status
• Trial end date: 2019-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the efficacy of an everolimus conversion (EVR) protocol as compared to the standard tacrolimus (TAC) based protocol in liver transplant recipients, as determined by renal function, rejection rates, and progression to fibrosis (in HCV positive subjects). Additionally, safety profile and tolerability of these regimens will be assessed.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tomoaki Kato
• Treatments: Everolimus; Mycophenolic Acid; Sirolimus; Tacrolimus

Criteria

Inclusion Criteria:

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

• Recipients of primary liver transplant from deceased or living donor

• 18 years of age or greater

• Lab Model For End-Stage Liver Disease (MELD) score ≤ 30

• Abbreviated Modification of Diet in Renal Disease (MDRD) eGFR ≥ 30 mL/min/1.73

Key Exclusion Criteria:

• Recipient of multiple solid or organ transplant, or have previously received and organ transplant

• Women of child-bearing potential unless they are willing to participate in adequate contraception methods as outlined in the study.

• HIV infection (results obtained 6 months prior to screening is acceptable)

Key Exclusion-Baseline/ Randamization

• Severe hypercholesterolemia (> 350 mg/dL) or hypertriglyceridemia (> 500 mg/dL) within 30 days prior to baseline.

• Thrombocytopenia (platelets < 50,000/mm3)

• Absolute neutrophil count of < 1000/mm3 or white blood cell count of < 2000/mm3

• Subjects in a critical care unit requiring life support measures such as mechanical ventilation, dialysis, requirement of vasopressor agents

• Liver allograft is functioning at an unacceptable level as defined by the Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Total Bilirubin levels > 3 times upper limit of normal (ULN) and Alkaline Phosphatase (AlkP) and Gamma-glutamyltransferase (GGT) levels > 5 times ULN

• Diagnosis of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis

• Hepatocellular carcinoma with evidence of macrovascular invasion on explanted liver or evidence of extrahepatic spread

• Inability to take medications by mouth

• Renal insufficiency, as defined by abbreviated MDRD eGFR < 30 mL/min/1.73m2, or requirement of dialysis, that does not recover prior to baseline

• Episode of acute rejection requiring antibody therapy or more than one steroid treated episode of acute rejection

• Subjects with a confirmed spot urine protein/creatinine ratio that indicates ≥1g/24h of proteinuria.

• Subtherapeutic trough levels of tacrolimus during the week prior to baseline (subject must have at least one tacrolimus level ≥ 8 ng/mL)

• The presence of thrombosis via Doppler ultrasound of the major hepatic arteries, major hepatic veins, portal vein and inferior vena cava.

• Presence of clinically significant wound