Clinical trial NCT00622869
Conditions: Liver Transplantation
Keywords: Liver transplantation everolimus calcineurin inhibitors tacrolimus renal function MDRD formula progression of fibrosis
Sponsor: Novartis Pharmaceuticals
Start date: 2008-01-01; Completion date: 2012-04-01
Enrollment: 719 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids. arm 2: Low-dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids. arm 3: Control dose tacrolimus + corticosteroids.
Interventions: intervention 1: Tacrolimus (reduced tacrolimus) intervention 2: Tacrolimus (tacrolimus elimination) intervention 3: Tacrolimus (tacrolimus control) intervention 4: Everolimus (reduced tacrolimus) intervention 5: Everolimus (tacrolimus elimination) intervention 6: Corticosteroids
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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. intervention 4: 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. intervention 5: 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. intervention 6: 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.

Protocol documents: