Clinical trial NCT01150097
Conditions: Liver Transplant Recipient
Keywords: Liver transplantation Everolimus Calcineurin inhibitors Tacrolimus Renal function Progression of HCV related allograft fibrosis
Sponsor: Novartis Pharmaceuticals
Start date: 2010-03-31; Completion date: 2013-05-03
Enrollment: 284 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The reason for this extension is to evaluate the long-term safety and efficacy of two concentration-controlled everolimus regimen in de novo liver transplant recipients. The most important long-term safety assessments include evaluation of renal function, progression of HCV related allograft fibrosis, and other treatment related effects at Month 36 post-transplantation compared to extension baseline (Months 24 post-transplantation).

Detailed description:

Arms: arm 1: Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus. arm 2: Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus. arm 3: Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
Interventions: intervention 1: Tacrolimus (reduced tacrolimus) intervention 2: Everolimus (reduced tacrolimus) intervention 3: Tacrolimus (tacrolimus elimination) intervention 4: Everolimus (tacrolimus elimination) intervention 5: Tacrolimus (tacrolimus control) 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: 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 3: 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 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 until Month 4; beginning with Month 4, the dose was adjusted to maintain everolimus trough blood levels between 6-10 ng/mL. intervention 5: 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 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. The corticosteroids were not specified in the protocol because they were adminsitered to the participants according to local practice as part of standard of care.

Protocol documents: