Renal TransplantationPhase 4NCT00154310
Efficacy and Safety of Everolimus With Enteric-Coated Mycophenolate Sodium (EC-MPS) in a Cyclosporine Microemulsion-free Regimen Compared to Standard Therapy in de Novo Renal Transplant Patients
A Phase 4 study testing Everolimus, Cyclosporine and Enteric-coated mycophenolate sodium in people with Renal Transplantation, run by Novartis at 3 sites in 2 countries.
Trial summary
The purpose of this study is to assess whether a calcineurin inhibitor (CNI)-free regimen with enteric-coated mycophenolate sodium (EC-MPS) and everolimus is as safe and well-tolerated as the standard regimen containing enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion, but results in better… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- Everolimus, Cyclosporine and Enteric-coated mycophenolate sodium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Jun 2005to Sep 2008
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The following inclusion criteria had to be present at BL 1 (Screening visit prior to transplantation):
- Males or females, aged 18 - 65 years
- Recipients of de novo cadaveric, living unrelated or living related kidney transplants
- Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at BL 1, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility
- Patients who are willing and able to participate in the study and from whom written informed consent has been obtained
- Of all patients included into the study at BL 1 (prior to transplantation), those who continued into the randomized study period had to meet the following condition at BL 2, prior to randomization:
- Patients had to be on an immunosuppressive regimen with EC-MPS (target dose; 1440 mg/day, if tolerated; minimal dose: 720 mg/day), cyclosporine and corticosteroids
- Patients with an actual serum creatinine =< 3.0 mg/dl
Who cannot join
- The following exclusion criteria must not be present at BL 1 (Screening visit prior to transplantation):
- More than one previous renal transplantation
- Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
- Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
- Patients who are recipients of A-B-O incompatible transplants
- Patients with a historical or current peak PRA of > 25%
Show all 14Show fewer
- Patients with already existing antibodies against the HLA-type of the receiving transplant
- Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception
- Of all patients included into the study at BL 1 (prior to transplantation), those who met one or more of the following criteria at BL 2, prior to randomization, should not continue into the randomized study period:
- Graft loss or death
- Changes to the immunosuppressive regimen prior to randomization due to immunologic reasons
- Patients who suffered from severe rejection (>= BANFF II acute rejection), recurrent acute rejection, or steroid resistant acute rejection
- Proteinuria > 1g/day
- Other protocol-defined exclusion criteria may apply.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Switzerland2 sites
Novartis Pharma AG
Basel
Novartis Investigational Sites
Bern
About this study
Official title: Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a CNI-free Regimen With Enteric-Coated Mycophenolate Sodium (EC-MPS) and Everolimus in Comparison to Standard Therapy With Enteric-Coated Mycophenolate Sodium (EC-MPS) and Cyclosporine Microemulsion in de Novo Renal Transplant Patients
The purpose of this study is to assess whether a calcineurin inhibitor (CNI)-free regimen with enteric-coated mycophenolate sodium (EC-MPS) and everolimus is as safe and well-tolerated as the standard regimen containing enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion, but results in better renal function.
- Conditions
- Renal Transplantation
- Being tested
- Everolimus, Cyclosporine, Enteric-coated mycophenolate sodium, Corticosteroids
- Keywords
- Renal transplantation, everolimus, immunosuppressants, CNI-free
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called certican
Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL.
CyclosporineDrug
Also called Sandimmun Optoral
Tablets orally twice a day to maintain protocol specific target blood levels
Enteric-coated mycophenolate sodiumDrug
Also called Myfortic
Enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day.
CorticosteroidsDrug
Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus + Mycophenolate sodium | Experimental | Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Receives: Drug: Everolimus; Drug: Enteric-coated mycophenolate sodium; Drug: Corticosteroids |
| Cyclosporine + Mycophenolate sodium | Active comparator | Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year. Receives: Drug: Cyclosporine; Drug: Enteric-coated mycophenolate sodium; Drug: Corticosteroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal Function (Nankivell Formula) at Month 12 Post Transplantation.
Renal function at the end of the trial assessed as mean absolute values of the glomerular filtration rate (GFR) calculated by Nankivell formula 12 months after renal transplantation. The Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)^2 + C ; where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. Estimated GFR is expressed in mL/min per 1.73m^2.
Measured: at Month 12 post transplantation
Secondary outcomes (4)
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death
The number of participants with occurrence of biopsy proven acute rejection (BPAR), graft loss, or death up to Month 12 during the randomized treatment period. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III according to Banff 97 classification. A graft core biopsy was performed prior to 24 hours following initiation of graft rejection therapy. The allograft is presumed to be lost on the day the patient starts dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
Measured: Up to Month 12
Number of Participants With Occurrence of Treatment Failures
Treatment failures defined as a composite endpoint of biopsy proven acute rejection, graft loss, death, loss to follow up and discontinuations due to lack of efficacy or toxicity, or conversion to another regimen (at least one condition must be present).
Measured: up to or at Month 12
Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12
An updated 1991 Framingham coronary prediction algorithm was used to estimate the total risk of developing coronary heart diseases (CHD) over the course of 10 years. Risk was calculated separately for male and females. To calculate risk, points were assigned for each of the following risk factors: age, levels of LDL cholesterol, HDL cholesterol, blood pressure, cigarette smoking, and diabetes mellitus. The sum of the individual risk factor points gives a total point score, which ranges from -5 to 18 for men and -16 to 24 for women. Higher points indicate a higher risk for CHD.
Measured: Month 4.5 and Month 12
Number of Participants Who Experienced an Adverse Event or Serious Adverse Event
Additional information about the number of participants who experienced Adverse Events (greater than 5%) or Serious Adverse Events can be found in the Adverse Event section.
Measured: Aes from end of core study period (month 12) to end of follow-up period (month 60)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startJun 2005
- Primary completionSep 2008
- Study completionSep 2008
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 (4)Papers the sponsor has linked to this study.
- Other trials for Renal TransplantationStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis, Study director, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00154310
- Sponsor's protocol ID
- CRAD001A2418
- Status last verified
- Oct 2013
- First submitted
- 8 Sep 2005
- Last updated
- 13 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Sommerer C, Witzke O, Lehner F, Arns W, Reinke P, Eisenberger U, Vogt B, Heller K, Jacobi J, Guba M, Stahl R, Hauser IA, Kliem V, Wuthrich RP, Muhlfeld A, Suwelack B, Duerr M, Paulus EM, Zeier M, Porstner M, Budde K; ZEUS and HERAKLES study investigators. Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials. BMC Nephrol. 2018 Sep 19;19(1):237. doi: 10.1186/s12882-018-1031-1.
PubMed 30231851Eisenberger U, Budde K, Lehner F, Sommerer C, Reinke P, Witzke O, Wuthrich RP, Stahl R, Heller K, Suwelack B, Muhlfeld A, Hauser IA, Nadalin S, Porstner M, Arns W; ZEUS Study Investigators. Histological findings to five years after early conversion of kidney transplant patients from cyclosporine to everolimus: an analysis from the randomized ZEUS study. BMC Nephrol. 2018 Jun 28;19(1):154. doi: 10.1186/s12882-018-0950-1.
PubMed 29954336Lehner F, Budde K, Zeier M, Wuthrich RP, Reinke P, Eisenberger U, Muhlfeld A, Arns W, Stahl R, Heller K, Witzke O, Wolters HH, Suwelack B, Klehr HU, Stangl M, Hauser IA, Nadalin S, Porstner M, May C, Paulus EM, Sommerer C; ZEUS Study Investigators. Efficacy and safety of conversion from cyclosporine to everolimus in living-donor kidney transplant recipients: an analysis from the ZEUS study. Transpl Int. 2014 Nov;27(11):1192-204. doi: 10.1111/tri.12411. Epub 2014 Aug 20.
PubMed 25070687Budde K, Becker T, Arns W, Sommerer C, Reinke P, Eisenberger U, Kramer S, Fischer W, Gschaidmeier H, Pietruck F; ZEUS Study Investigators. Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial. Lancet. 2011 Mar 5;377(9768):837-47. doi: 10.1016/S0140-6736(10)62318-5. Epub 2011 Feb 19.
PubMed 21334736
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a CNI-free Regimen With Enteric-Coated Mycophenolate Sodium (EC-MPS) and Everolimus in Comparison to Standard Therapy With Enteric-Coated Mycophenolate Sodium (EC-MPS) and Cyclosporine Microemulsion in de Novo Renal Transplant Patients
- ClinicalTrials.gov ID
- NCT00154310
- Acronym / sponsor ID
- CRAD001A2418
- Conditions
- Renal Transplantation
- Keywords
- Renal transplantation, everolimus, immunosuppressants, CNI-free
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Jun 2005
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Posted 24 May 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 this study is to assess whether a calcineurin inhibitor (CNI)-free regimen with enteric-coated mycophenolate sodium (EC-MPS) and everolimus is as safe and well-tolerated as the standard regimen containing enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion, but results in better renal function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus + Mycophenolate sodium | Experimental | Drug: Everolimus, Drug: Enteric-coated mycophenolate sodium, Drug: CorticosteroidsEverolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. |
| Cyclosporine + Mycophenolate sodium | Active comparator | Drug: Cyclosporine, Drug: Enteric-coated mycophenolate sodium, Drug: CorticosteroidsCyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The following inclusion criteria had to be present at BL 1 (Screening visit prior to transplantation):
- Males or females, aged 18 - 65 years
- Recipients of de novo cadaveric, living unrelated or living related kidney transplants
- Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at BL 1, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility
- Patients who are willing and able to participate in the study and from whom written informed consent has been obtained
Key exclusion criteria (14 listed)
- The following exclusion criteria must not be present at BL 1 (Screening visit prior to transplantation):
- More than one previous renal transplantation
- Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
- Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
- Patients who are recipients of A-B-O incompatible transplants
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: certicanEverolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL. | Drug | Everolimus + Mycophenolate sodium |
| CyclosporineAlso: Sandimmun OptoralTablets orally twice a day to maintain protocol specific target blood levels | Drug | Cyclosporine + Mycophenolate sodium |
| Enteric-coated mycophenolate sodiumAlso: MyforticEnteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. | Drug | Cyclosporine + Mycophenolate sodium, Everolimus + Mycophenolate sodium |
| CorticosteroidsCorticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year. | Drug | Cyclosporine + Mycophenolate sodium, Everolimus + Mycophenolate sodium |
Primary outcome
Renal Function (Nankivell Formula) at Month 12 Post Transplantation.
Time frame: at Month 12 post transplantation
Renal function at the end of the trial assessed as mean absolute values of the glomerular filtration rate (GFR) calculated by Nankivell formula 12 months after renal transplantation. The Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)^2 + C ; where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. Estimated GFR is expressed in mL/min per 1.73m^2.
4 secondary outcomes
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death
Time frame: Up to Month 12
Number of Participants With Occurrence of Treatment Failures
Time frame: up to or at Month 12
Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12
Time frame: Month 4.5 and Month 12
Number of Participants Who Experienced an Adverse Event or Serious Adverse Event
Time frame: Aes from end of core study period (month 12) to end of follow-up period (month 60)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30231851Sommerer C, Witzke O, Lehner F, Arns W, Reinke P, Eisenberger U, Vogt B, Heller K, Jacobi J, Guba M, Stahl R, Hauser IA, Kliem V, Wuthrich RP, Muhlfeld A, Suwelack B, Duerr M, Paulus EM, Zeier M, Porstner M, Budde K; ZEUS and HERAKLES study investigators. Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials. BMC Nephrol. 2018 Sep 19;19(1):237. doi: 10.1186/s12882-018-1031-1.
- Derived from this study: PubMed 29954336Eisenberger U, Budde K, Lehner F, Sommerer C, Reinke P, Witzke O, Wuthrich RP, Stahl R, Heller K, Suwelack B, Muhlfeld A, Hauser IA, Nadalin S, Porstner M, Arns W; ZEUS Study Investigators. Histological findings to five years after early conversion of kidney transplant patients from cyclosporine to everolimus: an analysis from the randomized ZEUS study. BMC Nephrol. 2018 Jun 28;19(1):154. doi: 10.1186/s12882-018-0950-1.
- Derived from this study: PubMed 25070687Lehner F, Budde K, Zeier M, Wuthrich RP, Reinke P, Eisenberger U, Muhlfeld A, Arns W, Stahl R, Heller K, Witzke O, Wolters HH, Suwelack B, Klehr HU, Stangl M, Hauser IA, Nadalin S, Porstner M, May C, Paulus EM, Sommerer C; ZEUS Study Investigators. Efficacy and safety of conversion from cyclosporine to everolimus in living-donor kidney transplant recipients: an analysis from the ZEUS study. Transpl Int. 2014 Nov;27(11):1192-204. doi: 10.1111/tri.12411. Epub 2014 Aug 20.
- Derived from this study: PubMed 21334736Budde K, Becker T, Arns W, Sommerer C, Reinke P, Eisenberger U, Kramer S, Fischer W, Gschaidmeier H, Pietruck F; ZEUS Study Investigators. Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial. Lancet. 2011 Mar 5;377(9768):837-47. doi: 10.1016/S0140-6736(10)62318-5. Epub 2011 Feb 19.
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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 study director
Novartis
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus, Cyclosporine and Enteric-coated mycophenolate sodium in people with Renal Transplantation, run by Novartis at 3 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 8 inclusion and 14 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 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Switzerland, Germany. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 24 May 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?
Renal Function (Nankivell Formula) at Month 12 Post Transplantation. (time frame: at Month 12 post transplantation). 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 NCT00154310, which also lists 4 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 Nov 2013.