NCT01150097

Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients

Extension Study to the Multicenter, Open-label, Randomized, Controlled Study CRAD001H2304 to Evaluate the Long-term Efficacy and Safety of Concentration-controlled Everolimus in Liver Transplant Recipient

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 284 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 20 Years – 75 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Liver Transplant Recipient

Interventions

Type	Name	Description
DRUG	Tacrolimus (reduced tacrolimus)	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.
DRUG	Everolimus (reduced tacrolimus)	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.
DRUG	Tacrolimus (tacrolimus elimination)	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.
DRUG	Everolimus (tacrolimus elimination)	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.
DRUG	Tacrolimus (tacrolimus control)	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.
DRUG	Corticosteroids	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.

Timeline

• Start date: 2010-03-31
• Primary completion: 2013-05-03
• Completion: 2013-05-03
• First posted: 2010-06-24
• Last updated: 2018-11-07
• Results posted: 2014-05-30

Locations

57 sites across 16 countries: United States, Argentina, Australia, Belgium, Brazil, Colombia, Czechia, France, Germany, Ireland, Italy, Netherlands, Russia, Spain, Sweden, United Kingdom