- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00267189
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
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Germany, Germany
- Novartis Investigational site
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Basel, Switzerland
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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ACTIVE_COMPARATOR: Reduced CNI dose + everolimus ± steroids
Reduced CNI dose + everolimus (1.5 mg twice daily (b.i.d)) ± steroids
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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:
Other Names:
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EXPERIMENTAL: CNI continuation ± MPA/AZA ± Steroids
Standard CNI dose ± MPA/AZA ± steroids
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Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Change From Baseline in Cockcroft-Gault Calculated Creatinine Clearance (CrCl)
Time Frame: From baseline to 6 months
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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. |
From baseline to 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)
Time Frame: 6 months
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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.
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6 months
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Number of Patients With Discontinuation of Study Medication
Time Frame: 6 months
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6 months
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Antifungal Agents
- Azathioprine
- Tacrolimus
- Everolimus
- Cyclosporine
- Cyclosporins
- Calcineurin Inhibitors
Other Study ID Numbers
- CRAD001H2401
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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