Twice-daily Tacrolimus and Everolimus Convert to Once-daily Tacrolimus and Everolimus in Liver Transplant Recipient
Condition: Liver Transplantation
Study type: Interventional
Phase: Phase 4

Summary: 
      It has been identified that nonadherence to immunosuppressant regimen may cause long-term
      graft failure and death in solid organ transplant recipients. Therefore, simplification of
      the immunosuppression regimen by reducing daily dosing frequency may improve long-term
      outcome. The investigators will examine pharmacokinetics and safety profiles of stable liver
      transplant recipients receiving twice-daily TAC with EVR (BID) regimen and then being
      converted to once-daily TAC with EVR (QD) regimen over a 6-month study period
      post-conversion.
    

Detailed description: 
      Randomized trial of everolimus (EVR) with reduced tacrolimus (TAC) regimen after liver
      transplantation has shown similar incidence of composite efficacy failure rate to a standard
      tacrolimus regimen, but with superior renal function for up to three years. Recent studies
      have demonstrated comparable efficacy and safety profiles in liver transplant recipients
      receiving tacrolimus once-daily (QD) and tacrolimus twice-daily (BID) regimens. In kidney
      transplantation, once daily everolimus (QD) regimen has shown its safety and effectiveness.
      It has been identified that nonadherence to immunosuppressant regimen may cause long-term
      graft failure and death in solid organ transplant recipients. Therefore, simplification of
      the immunosuppression regimen (e.g. TAC with EVR) by reducing daily dosing frequency may
      improve long-term outcome. However, little is known about the effectiveness and safety of
      combined TAC and EVR once-daily (QD) regimen in liver transplant recipients. The investigator
      will examine pharmacokinetics and safety profiles of stable liver transplant recipients
      receiving twice-daily TAC with EVR (BID) regimen and then being converted to once-daily TAC
      with EVR (QD) regimen over a 6-month study period post-conversion.
    

Intervention name(s): Tacrolimus and Everolimus
Intervention type(s): Drug
Intervention description(s): In the TAC and EVR BID arm, everolimus will be initiated at a dose of 1.0 mg BID within 24 h of randomization with the dose adjusted from day 5 onward to maintain trough (C0) concentration in the range 3-8 ng/mL. Tacrolimus will be initiated at a dose of 0.15 mg/kg BID and then taper to 0.10 mg/kg BID to maintain trough (C0) concentration in the range 2.5-5 ng/mL.
In the TAC and EVR QD arm, everolimus will be initiated at a dose of 2.0 mg QD within 24 h of randomization with the dose adjusted from day 5 onward to maintain trough (C0) concentration in the range 3-8 ng/mL. Tacrolimus will be initiated at a dose of 0.1-0.2 mg/kg/day QD to maintain trough (C0) concentration in the range 2.5-5 ng/mL.
Other intervention name(s): Prograf; Advagraf; Zortress; Certican
Intervention MeSH terms: Everolimus; Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other