Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients

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.

Conditions

• Liver Transplantation

Interventions

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

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

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

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

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

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.

Sponsors & Collaborators

• Novartis Pharmaceuticals

  lead INDUSTRY

Principal Investigators

• Novartis Pharmaceuticals · Novartis Pharmaceuticals

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-01-31

Primary Completion

2012-04-30

Completion

2012-04-30

Countries

• United States
• Argentina
• Australia
• Belgium
• Brazil
• Canada
• Colombia
• Czechia
• France
• Germany
• Hungary
• Ireland
• Israel
• Italy
• Netherlands
• Russia
• Spain
• Sweden
• United Kingdom

Study Locations