RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency

Novartis

Status and phase: Completed; Phase 3

Conditions: Liver Transplantation

Treatments: Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA); Drug: Steroids; Drug: Everolimus; Drug: Calcineurin inhibitors (CNI)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00267189

CRAD001H2401

Details and patient eligibility

About

The purpose of the study is to assess the effect of everolimus initiation together with reduction or discontinuation of calcineurin inhibitor (CNI) on renal function in maintenance liver transplant recipients with CNI-related renal impairment, while maintaining efficacy.

Enrollment: 145 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

• Male or female 18 - 70 years old
• Patient who has undergone a primary liver transplantation 12 to 60 months ago from a cadaveric or a living donor
• Patient with a calculated GFR ≤ 60 and ≥ 20mL/min
• Patient receiving tacrolimus with C0-h level ≥ 3 and ≤ 8 ng/mL or Neoral® with C0-h level ≥ 50 and ≤ 150 ng/mL or with C2-h level ≥ 250 ng/mL and ≤ 650 ng/mL with or without any of the following (MPA or AZA or steroids)
• Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 6 months
• Patient in whom an allograft biopsy will not be contraindicated
• Female capable of becoming pregnant must have a negative pregnancy test prior to randomization and are required to practice a medically approved method of birth control for the duration of the study

Exclusion criteria

• Recipient of multiple solid organ transplants
• Patient on dialysis
• Patient with an identifiable cause of renal dysfunction other than CNI toxicity
• Patient with proteinuria ≥ 1.0 g/24h
• Patient with any acute rejection within 6 months prior to randomization
• Patient with platelet count of ≤ 50,000/mm³ or white blood cell count of ≤ 2,000/mm³ or hemoglobin value ≤ 8 g/dL
• Undergone a liver transplantation for a hepatocellular carcinoma with sign of recurrence;
• Severe graft dysfunction;
• HCV positive patient who needs an active anti-viral treatment
• HIV positive patient
• Patient who is breast feeding
• Patient with a current severe systemic infection
• Patient who has received an unlicensed drug or therapy within one month prior to study entry
• Presence of any hypersensitivity to drugs similar to everolimus (e.g. macrolides)
• Use of any other immunosuppressive drugs than tacrolimus/cyclosporine microemulsion, steroids, azathioprine and mycophenolic acid

Additional protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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145 participants in 2 patient groups

Reduced CNI dose + everolimus ± steroids

Active Comparator group

Description:

Reduced CNI dose + everolimus (1.5 mg twice daily (b.i.d)) ± steroids

Treatment:

Drug: Calcineurin inhibitors (CNI)

Drug: Everolimus

Drug: Steroids

CNI continuation ± MPA/AZA ± Steroids

Experimental group

Description:

Standard CNI dose ± MPA/AZA ± steroids

Treatment:

Drug: Calcineurin inhibitors (CNI)

Drug: Steroids

Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA)