RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00267189
Recruitment Status : Completed
First Posted : December 20, 2005
Results First Posted : April 7, 2011
Last Update Posted : April 13, 2011
Information provided by:

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.

Condition or disease Intervention/treatment Phase
Liver Transplantation Drug: Everolimus Drug: Calcineurin inhibitors (CNI) Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA) Drug: Steroids Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 145 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : November 2005
Actual Primary Completion Date : November 2007
Actual Study Completion Date : November 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Reduced CNI dose + everolimus ± steroids
Reduced CNI dose + everolimus (1.5 mg twice daily (b.i.d)) ± steroids
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: Steroids
Experimental: CNI continuation ± MPA/AZA ± Steroids
Standard CNI dose ± MPA/AZA ± steroids
Drug: Calcineurin inhibitors (CNI)
Other Name: Neoral/Prograf
Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA)
Other Name: Myfortic/Cellecept
Drug: Steroids

Primary Outcome Measures :
  1. Mean Change From Baseline in Cockcroft-Gault Calculated Creatinine Clearance (CrCl) [ Time Frame: From baseline to 6 months ]

    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.

Secondary Outcome Measures :
  1. Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death) [ Time Frame: 6 months ]
    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.

  2. Number of Patients With Discontinuation of Study Medication [ Time Frame: 6 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00267189

Novartis Investigational Site
Germany, Germany
Novartis Investigative Site
Basel, Switzerland
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: External Affairs, Novartis Pharmaceuticals Identifier: NCT00267189     History of Changes
Other Study ID Numbers: CRAD001H2401
First Posted: December 20, 2005    Key Record Dates
Results First Posted: April 7, 2011
Last Update Posted: April 13, 2011
Last Verified: April 2011

Keywords provided by Novartis:
Liver transplantation, everolimus, calcineurin inhibitor, renal function

Additional relevant MeSH terms:
Calcineurin Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antirheumatic Agents
Dermatologic Agents