Clinical trial NCT00267189: RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency
Official title: A 6-month, Multicenter, Randomized, Open-label Study of Safety and Efficacy of Everolimus-based Regimen Versus Calcineurin Inhibitor (CNI)-Based Regimen in Maintenance Liver Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Transplantation
Keywords: Liver transplantation, everolimus, calcineurin inhibitor, renal function
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-12-20
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Mean Change From Baseline in Cockcroft-Gault Calculated Creatinine Clearance (CrCl)
timeFrame: From baseline to 6 months
Secondary outcomes:
measure: Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)
timeFrame: 6 months
measure: Number of Patients With Discontinuation of Study Medication
timeFrame: 6 months
Other outcomes:
Locations:
city: Germany
country: Germany
facility: Novartis Investigational Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: De Simone P, Metselaar HJ, Fischer L, Dumortier J, Boudjema K, Hardwigsen J, Rostaing L, De Carlis L, Saliba F, Nevens F. Conversion from a calcineurin inhibitor to everolimus therapy in maintenance liver transplant recipients: a prospective, randomized, multicenter trial. Liver Transpl. 2009 Oct;15(10):1262-9. doi: 10.1002/lt.21827.
citation: Schrader J, Sterneck M, Klose H, Lohse AW, Nashan B, Fischer L. Everolimus-induced pneumonitis: report of the first case in a liver transplant recipient and review of treatment options. Transpl Int. 2010 Jan;23(1):110-3. doi: 10.1111/j.1432-2277.2009.00900.x. Epub 2009 May 29. No abstract available.