Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients
Condition: Liver Transplantation
Study type: Interventional
Phase: Phase 3

Summary: 
      This trial was designed to address important issues that impact recipients of liver
      allografts as well as clinicians, ie, renal function, reduction or discontinuation of
      tacrolimus early post-transplantation, and progression rate of fibrosis in hepatitis C virus
      (HCV) positive patients.
    

Detailed description: 
      This 24-month study consisted of a screening period, a baseline period (3 to 7 days
      post-transplantation) followed by a run-in period that ended on the day of randomization at
      30 days (± 5 days) post-transplantation. Patients were screened for eligibility prior to
      liver transplantation. Patients who had undergone successful liver transplantation were
      initiated on a tacrolimus-based regimen that included corticosteroids and entered the
      baseline period (between 3 and 7 days post-transplantation). At 30 (± 5) days
      post-transplantation, patients who met additional randomization inclusion/exclusion criteria
      were randomized into the study.
    

Intervention name(s): Tacrolimus (reduced tacrolimus); Tacrolimus (tacrolimus elimination); Tacrolimus (tacrolimus control); Everolimus (reduced tacrolimus); Everolimus (tacrolimus elimination); Corticosteroids
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization, a level which was maintained for the duration of the study.; After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization. Tacrolimus elimination was started beginning at Month 4. Tacrolimus was tapered after everolimus whole blood trough levels were within the target range of 6-10 ng/mL. Tacrolimus was completely eliminated by the end of Month 4.; Tacrolimus trough levels were targeted to be maintained at 8-12 ng/mL until Month 4. At Month 4, tacrolimus whole blood trough levels were decreased to a target trough level of 6-10 ng/mL for the remainder of the study.; Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL for the duration of the study.; Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL until Month 4; beginning with Month 4, the dose was adjusted to maintain everolimus trough blood levels between 6-10 ng/mL.; For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids could be used for the duration of the study but could not be eliminated before Month 6.
Other intervention name(s): FK-506; fujimycin; Prograf; Advagraf; Protopic; FK-506; fujimycin; Prograf; Advagraf; Protopic; FK-506; fujimycin; Prograf; Advagraf; Protopic; RAD-001; Zortress; Certican; Afinitor; RAD-001; Zortress; Certican; Afinitor
Intervention MeSH terms: Everolimus; Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Liver transplantation; everolimus; calcineurin inhibitors; tacrolimus; renal function; MDRD formula; progression of fibrosis