Study Comparing in Livertransplantation Recipients With Tacrolimus Alone Versus Tacrolimus&Sirolimus
Condition: Liver Disease
MeSH terms: Liver Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      In this study we compare long term renal function in liver transplantation recipients treated
      with standard dose extended-release tacrolimus alone and recipients treated with a
      combination of low dose extended-release tacrolimus and low dose sirolimus. The hypothesis is
      that the patients treated with the combination have better long term renal function than the
      patients treated with standard dose tacrolimus alone.
    

Detailed description: 
      To evaluate the effectiveness and safety of concentration controlled combination of once
      daily dosed low-dose sirolimus (trough levels: 3-5 ng/ml) and extended-release tacrolimus
      (trough levels:3-5 ng/ml), in order to provide superior renal function while maintaining
      comparable rates of patient and graft survival, compared to concentration controlled once -
      daily extended release tacrolimus (trough levels: 5-10 ng/ml) at 12, 24 and 36 months
      post-transplant. Moreover, to compare the incidence of de novo malignancy, the quality of
      life, fatigue and side effects between both treatment arms.

      2.1 Primary objectives: To evaluate the effectiveness and safety of concentration controlled
      combination of low-dose sirolimus (trough levels: 3-5 ng/ml) and extended-release tacrolimus
      (trough levels: 3-5 ng/ml), in order to provide superior renal function while maintaining
      comparable rates of patient and graft survival, compared to concentration controlled once -
      daily extended release tacrolimus (trough levels:-10 ng/ml) control at 12, 24 and 36 months
      post-transplant.

      2.2. Secondary objectives:

        -  To compare the incidence of de novo and recurrence of cancer between study arm and
           control arm at 36 months.

        -  To compare the incidence and severity of biopsy proven acute rejection between study arm
           and control arm at 12, 24 and 36 months.

        -  To evaluate renal function at 12, 24 and 36 months (calculated GFR).

        -  To evaluate the development of new onset diabetes mellitus at 12, 24 and 36 months post
           transplant

        -  To evaluate the prevalence of CNI side effects at 12, 24 and 36 months

        -  To evaluate quality of life (Eq5D) and fatigue severity score at 12, 24 and 36 months

        -  To evaluate the percentage of patients on combination tacrolimus and sirolimus and
           converted back to tacrolimus mono-therapy.
    

Intervention name(s): Tacrolimus and Sirolimus; Tacrolimus
Intervention type(s): Drug; Drug
Intervention description(s): Arm 1 once daily combination therapy of normal dosed extended-release tacrolimus and prednisone for 3 months and monotherapy once daily extended-release tacrolimus thereafter up to 3 years after liver transplantation.
Arm 2 once daily combination therapy of low doses sirolimus and extended-release tacrolimus and prednisone for 3 months and combination therapy of low dose sirolimus and extended-release tacrolimus thereafter for up to 3 years after liver transplantation Continue Advagraf (5-10 ng/ml) and 7.5 mg prednison; lower or discontinue steroids after day 180 at the discretion of the treating physician Conversion to sirolimus (3-5 ng/ml) and decrease Advagraf (3-5 ng/ml); 7.5 mg prednisone and lower or discontinue steroids after day 180 at the discretion of the treating physician; Patient received standard-dose of Tracrolimus Advagraf (5-10 ng/ml) and 7.5 mg prednison; lower or discontinue steroids after day 180 at the discretion of the treating physician
Other intervention name(s): Advagraf [Astellas Pharma bv); Rapamune; Advagraf
Intervention MeSH terms: Sirolimus; Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Liver transplantation long term renal function; tacrolimus sirolimus