Liver TransplantationPhase 3NCT00267189
RESCUE Study - Everolimus in Liver Transplantation Recipients With Renal Insufficiency
A Phase 3 study testing Everolimus, Calcineurin inhibitors (CNI) and Mycophenolate acid (MPA)/ Azathioprine (AZA) in people with Liver Transplantation, run by Novartis Pharmaceuticals at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Everolimus, Calcineurin inhibitors (CNI) and Mycophenolate acid (MPA)/ Azathioprine (AZA)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 145 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Nov 2005to Nov 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
- Conditions
- Liver Transplantation
- Being tested
- Everolimus, Calcineurin inhibitors (CNI), Mycophenolate acid (MPA)/ Azathioprine (AZA), Steroids
- Keywords
- Liver transplantation, everolimus, calcineurin inhibitor, renal function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Certican, RAD001, Neoral®/Prograf®
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
Calcineurin inhibitors (CNI)Drug
Also called Neoral/Prograf
Mycophenolate acid (MPA)/ Azathioprine (AZA)Drug
Also called Myfortic/Cellecept
SteroidsDrug
| Study group | Role | What they receive |
|---|---|---|
| Reduced CNI dose + everolimus ± steroids | Active comparator | Reduced CNI dose + everolimus (1.5 mg twice daily (b.i.d)) ± steroids Receives: Drug: Everolimus; Drug: Calcineurin inhibitors (CNI); Drug: Steroids |
| CNI continuation ± MPA/AZA ± Steroids | Experimental | Standard CNI dose ± MPA/AZA ± steroids Receives: Drug: Calcineurin inhibitors (CNI); Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA); Drug: Steroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in Cockcroft-Gault Calculated Creatinine Clearance (CrCl)
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.
Measured: From baseline to 6 months
Secondary outcomes (2)
Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)
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.
Measured: 6 months
Number of Patients With Discontinuation of Study Medication
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2005 (estimated)
- Study startNov 2005
- Primary completionNov 2007
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00267189
- Sponsor's protocol ID
- CRAD001H2401
- Status last verified
- Apr 2011
- First submitted
- 19 Dec 2005
- Last updated
- 13 Apr 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 19790150Schrader 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.
PubMed 19497063
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00267189
- Acronym / sponsor ID
- CRAD001H2401
- Conditions
- Liver Transplantation
- Keywords
- Liver transplantation, everolimus, calcineurin inhibitor, renal function
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2005
- Primary completion
- Nov 2007 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 20 Dec 2005 (estimated)
- Results
- Posted 7 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Reduced CNI dose + everolimus ± steroids | Active comparator | Drug: Everolimus, Drug: Calcineurin inhibitors (CNI), Drug: SteroidsReduced CNI dose + everolimus (1.5 mg twice daily (b.i.d)) ± steroids |
| CNI continuation ± MPA/AZA ± Steroids | Experimental | Drug: Calcineurin inhibitors (CNI), Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA), Drug: SteroidsStandard CNI dose ± MPA/AZA ± steroids |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: Certican, RAD001, Neoral®/Prograf®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 | Drug | Reduced CNI dose + everolimus ± steroids |
| Calcineurin inhibitors (CNI)Also: Neoral/Prograf | Drug | CNI continuation ± MPA/AZA ± Steroids, Reduced CNI dose + everolimus ± steroids |
| Mycophenolate acid (MPA)/ Azathioprine (AZA)Also: Myfortic/Cellecept | Drug | CNI continuation ± MPA/AZA ± Steroids |
| Steroids | Drug | CNI continuation ± MPA/AZA ± Steroids, Reduced CNI dose + everolimus ± steroids |
Primary outcome
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.
2 secondary outcomes
Percentage of Patients With Efficacy Failure (Biopsy Proven Acute Rejection [BPAR], Graft Loss or Death)
Time frame: 6 months
Number of Patients With Discontinuation of Study Medication
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19790150De 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.
- Derived from this study: PubMed 19497063Schrader 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Everolimus, Calcineurin inhibitors (CNI) and Mycophenolate acid (MPA)/ Azathioprine (AZA) in people with Liver Transplantation, run by Novartis Pharmaceuticals at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in Cockcroft-Gault Calculated Creatinine Clearance (CrCl) (time frame: From baseline to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00267189, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2011.