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

NCT ID: NCT00154310

Last Updated: 2013-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2008-09-30

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.

Conditions

Renal Transplantation

Keywords

Renal transplantation, everolimus, immunosuppressants, CNI-free

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus + Mycophenolate sodium

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.

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL.

Enteric-coated mycophenolate sodium

Intervention Type: DRUG

Enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day.

Corticosteroids

Intervention Type: DRUG

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.

Cyclosporine + Mycophenolate sodium

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.

Group Type: ACTIVE_COMPARATOR

Cyclosporine

Intervention Type: DRUG

Tablets orally twice a day to maintain protocol specific target blood levels

Enteric-coated mycophenolate sodium

Intervention Type: DRUG

Enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day.

Corticosteroids

Intervention Type: DRUG

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.

Interventions

Everolimus

Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL.

Intervention Type: DRUG

Cyclosporine

Tablets orally twice a day to maintain protocol specific target blood levels

Intervention Type: DRUG

Enteric-coated mycophenolate sodium

Enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day.

Intervention Type: DRUG

Corticosteroids

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.

Intervention Type: DRUG

Other Intervention Names

certican; Sandimmun Optoral; Myfortic

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis

Role: STUDY_DIRECTOR

Novartis

Locations

Novartis Investigational Sites

Nuremberg, , Germany

Novartis Pharma AG

Basel, , Switzerland

Novartis Investigational Sites

Bern, , Switzerland

Countries

Germany; Switzerland

References

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.

Reference Type: DERIVED

PMID: 30231851 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29954336 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25070687 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21334736 (View on PubMed)

Other Identifiers

CRAD001A2418

Identifier Type: -

Identifier Source: org_study_id