Clinical trial NCT00154310: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplantation
Keywords: Renal transplantation, everolimus, immunosuppressants, CNI-free
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 renal function.


Eligibility criteria: Inclusion Criteria :

The following inclusion criteria had to be present at BL 1 (Screening visit prior to transplantation):

1. Males or females, aged 18 - 65 years
2. Recipients of de novo cadaveric, living unrelated or living related kidney transplants
3. 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
4. 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:
5. 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
6. Patients with an actual serum creatinine =\< 3.0 mg/dl

Exclusion Criteria:

The following exclusion criteria must not be present at BL 1 (Screening visit prior to transplantation):

1. More than one previous renal transplantation
2. Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
3. Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
4. Patients who are recipients of A-B-O incompatible transplants
5. Patients with a historical or current peak PRA of \> 25%
6. Patients with already existing antibodies against the HLA-type of the receiving transplant
7. 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:
8. Graft loss or death
9. Changes to the immunosuppressive regimen prior to randomization due to immunologic reasons
10. Patients who suffered from severe rejection (\>= BANFF II acute rejection), recurrent acute rejection, or steroid resistant acute rejection
11. Proteinuria \> 1g/day

Other protocol-defined exclusion criteria may apply.

Primary outcomes:
measure: Renal Function (Nankivell Formula) at Month 12 Post Transplantation.
timeFrame: at Month 12 post transplantation
Secondary outcomes:
measure: Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death
timeFrame: Up to Month 12
measure: Number of Participants With Occurrence of Treatment Failures
timeFrame: up to or at Month 12
measure: Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12
timeFrame: Month 4.5 and Month 12
measure: Number of Participants Who Experienced an Adverse Event or Serious Adverse Event
timeFrame: Aes from end of core study period (month 12) to end of follow-up period (month 60)
Other outcomes:
Locations:
city: Nurnberg
country: Germany
facility: Novartis Investigational Sites
city: Basel
country: Switzerland
facility: Novartis Pharma AG
city: Bern
country: Switzerland
facility: Novartis Investigational Sites
Study officials:
affiliation: Novartis
name: Novartis
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Eisenberger 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.
citation: Lehner 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.
citation: Budde 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.