Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.
Condition: Renal Function; Liver Transplant
Intervention: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation.
Intervention description: Immunosuppression after liver transplantation. Pediatric transplant recipients received a starting dose of 0.8 mg/m^2/dose in combination wit Cyclosporine A or 2.0 mg/m^2/dose in combination with tacrolimus, twice-daily. Thereafter, doses were adjusted to achieve everolimus C-0h blood trough level between 3 to 8 ng/ml.
Intervention MeSH terms: Cyclosporine; Everolimus; Tacrolimus; Cyclosporins
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 1 Month
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Paediatric liver transplantation; Everolimus; Reduced calcineurin inhibitor; Cyclosporine, tacrolimus; Renal function; Composite efficacy endpoint (treated biopsy proven acute rejection death, graft loss); Liver transplant

Summary:

      This study was designed to assess the evolution of renal function and to collect efficacy,
      safety, and tolerability data of everolimus in co-exposure with reduced CNI in paediatric
      liver transplant recipients.
    

Eligibility criteria:

        Key Inclusion Criteria:

        Signed informed consent from both parents or legal guardian(s) prior to patient
        participation in the study.

        Paediatric liver transplant recipients aged greater than or equal to 1 month and younger
        than 18 years of age.

        Paediatric recipients at the earliest 1 month and latest 6 month after liver
        transplantation.

        Key Exclusion Criteria:

        Patients with hepato-biliary malignancies and/or patients transplanted due to fulminant
        hepatitis /acute liver failure.

        Presence of thrombosis of any major hepatic arteries, major/reconstructed hepatic veins,
        portal vein or inferior vena cava at any time prior to the start of study drug.

        Patients with serum creatinine value >2 times age-related ULN at Baseline or who received
        renal replacement therapy within one week prior to the start of study drug and patients
        with a confirmed spot urine protein/creatinine ratio indicating a urinary protein excretion
        >500 mg/m2/24 hrs, at Baseline.

        Patients with clinically significant systemic infection and/or in a critical care setting
        requiring life support measures such as mechanical ventilation, dialysis, or vasopressor
        agents.

        Patients with a known hypersensitivity to the drugs used on study or their class, or to any
        of the excipients.

        Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of
        a female after conception and until the termination of gestation, confirmed by a positive
        βHCG laboratory test (>9 mIU/mL) at Baseline.

        Female patients of child-bearing potential, defined as all women physiologically capable of
        becoming pregnant, UNLESS they agree for abstinence from sexual activity.