RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00267189
First received: December 19, 2005
Last updated: April 11, 2011
Last verified: April 2011

December 19, 2005
April 11, 2011
November 2005
November 2007   (final data collection date for primary outcome measure)
Mean Change From Baseline in Cockcroft-Gault Calculated Creatinine Clearance (CrCl) [ Time Frame: From baseline to 6 months ] [ Designated as safety issue: No ]

The primary variable was renal function assessed by calculated creatinine clearance using the Cockcroft-Gault formula, and was assessed at all visits.

CrCl[mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit [kg], C is the serum concentration of creatinine [mg/dL], R = 1 if the patient is male and = 0.85 if female.

Not Provided
Complete list of historical versions of study NCT00267189 on ClinicalTrials.gov Archive Site
  • Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The composite efficacy failure endpoint encompasses at least one of: biopsy proven acute rejection, graft loss, or death for the patient. BPAR was defined as a clinically suspected acute rejection confirmed by biopsy. Acute rejection episodes were recorded as Liver Allograft Rejection. The allograft was presumed to be lost if a patient had a liver retransplant or died.
  • Number of Patients With Discontinuation of Study Medication [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
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RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Liver Transplantation
  • Drug: Everolimus
    1.5 mg bid adjusted in order to achieve a trough level between 3 and 8 ng/mL while in combination with CNI and between 6 and 12 ng/mL after CNI discontinuation
    Other Names:
    • Certican
    • RAD001
    • Neoral®/Prograf®
  • Drug: Calcineurin inhibitors (CNI)
    Other Name: Neoral/Prograf
  • Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA)
    Other Name: Myfortic/Cellecept
  • Drug: Steroids
  • Active Comparator: Reduced CNI dose + everolimus ± steroids
    Reduced CNI dose + everolimus (1.5 mg twice daily (b.i.d)) ± steroids
    Interventions:
    • Drug: Everolimus
    • Drug: Calcineurin inhibitors (CNI)
    • Drug: Steroids
  • Experimental: CNI continuation ± MPA/AZA ± Steroids
    Standard CNI dose ± MPA/AZA ± steroids
    Interventions:
    • Drug: Calcineurin inhibitors (CNI)
    • Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA)
    • Drug: Steroids

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
145
November 2007
November 2007   (final data collection date for primary outcome measure)

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.

Both
18 Years to 70 Years
Not Provided
Contact information is only displayed when the study is recruiting subjects
Germany,   Switzerland
 
NCT00267189
CRAD001H2401
Yes
External Affairs, Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP