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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
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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 ]

Enrollment: 145
Study Start Date: November 2005
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00267189

Locations
Germany
Novartis Investigational Site
Germany, Germany
Switzerland
Novartis Investigative Site
Basel, Switzerland
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00267189     History of Changes
Other Study ID Numbers: CRAD001H2401
Study First Received: December 19, 2005
Results First Received: December 20, 2010
Last Updated: April 11, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

Additional relevant MeSH terms:
Azathioprine
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014