Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a Calcineurin Inhibitor (CNI)-Free Regimen and a CNI-low Dose Regimen

NCT ID: NCT00514514

Last Updated: 2017-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 802 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2015-06-30

Brief Summary

The purpose of this study is to compare renal function of immunosuppressive regimens with different relevance of the calcineurin inhibitor (CNI) cyclosporine: standard dose CNI, low dose CNI, CNI free in de novo kidney transplant patients after 12 months of therapy.

Conditions

Kidney Transplantation

Study Design

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

Study Groups

CNI standard regimen

Myfortic, Sandimmun Optoral and corticosteroids

Group Type: ACTIVE_COMPARATOR

Myfortic

Intervention Type: DRUG

1 tablet containing 180 mg or 360 mg

Dosing schedule:

Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen) According to blood level 1440 mg/day (2 x 720 mg), if tolerated. Dose reduction possible in case of side effects (min. dose at BL2 (Month 3): 720 mg/day)

Sandimmun Optoral

Intervention Type: DRUG

1 capsule containing 10, 25, 50, or 100mg. Dosing: According to blood level

Simulect®

Intervention Type: DRUG

Lyophilisate in vials with ampoules of sterile water for injection (5 ml). Dosing: 1 vial containing 20 mg lyophilisate. Dosing schedule: 2 x 20 mg to be applied as 10 sec. bolus injection, i.v. on Day 0 (2 h before transplant) and on Day 4

CNI free regimen

CNI free regimen: comprising the following steps for switching treatment:

Step 1 at BL2 + 1 day: Myfortic, Certican 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, Certican 3 mg and corticosteroids

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Tablet containing 0.5 mg or 0.75 mg. Dosing schedule: Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen

Myfortic

Intervention Type: DRUG

1 tablet containing 180 mg or 360 mg

Dosing schedule:

Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen) According to blood level 1440 mg/day (2 x 720 mg), if tolerated. Dose reduction possible in case of side effects (min. dose at BL2 (Month 3): 720 mg/day)

Sandimmun Optoral

Intervention Type: DRUG

1 capsule containing 10, 25, 50, or 100mg. Dosing: According to blood level

CNI low regimen

CNI low regimen: comprising the following steps for switching treatment:

Step 1 at BL2 + 1 day: Certican 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: Certican 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids

Group Type: ACTIVE_COMPARATOR

Everolimus

Intervention Type: DRUG

Tablet containing 0.5 mg or 0.75 mg. Dosing schedule: Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen

Sandimmun Optoral

Intervention Type: DRUG

1 capsule containing 10, 25, 50, or 100mg. Dosing: According to blood level

Interventions

Everolimus

Tablet containing 0.5 mg or 0.75 mg. Dosing schedule: Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen

Intervention Type: DRUG

Myfortic

1 tablet containing 180 mg or 360 mg

Dosing schedule:

Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen) According to blood level 1440 mg/day (2 x 720 mg), if tolerated. Dose reduction possible in case of side effects (min. dose at BL2 (Month 3): 720 mg/day)

Intervention Type: DRUG

Sandimmun Optoral

1 capsule containing 10, 25, 50, or 100mg. Dosing: According to blood level

Intervention Type: DRUG

Simulect®

Lyophilisate in vials with ampoules of sterile water for injection (5 ml). Dosing: 1 vial containing 20 mg lyophilisate. Dosing schedule: 2 x 20 mg to be applied as 10 sec. bolus injection, i.v. on Day 0 (2 h before transplant) and on Day 4

Intervention Type: DRUG

Other Intervention Names

Certican; Enteric Coated Mycophenolate Sodium; Cyclosporine A; Basiliximab

Eligibility Criteria

Inclusion Criteria

• Males or females, aged 18 - 70 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 screening, 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.

Exclusion Criteria

• More than one previous renal transplantation
• Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
• Patients receiving a kidney from a non-heart beating donor
• Donor age: < 5 years or > 70 years
• Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Novartis

Role: STUDY_DIRECTOR

Novartis

Locations

Novartis Investigative Site

Aachen, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Frankfurt am Main, , Germany

Novartis Investigative Site

Freiburg im Breisgau, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Hannover Muenden, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Kaiserslautern, , Germany

Novartis Investigative Site

Lübeck, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Regensburg, , Germany

Novartis Investigative Site

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)

Budde K, Zeier M, Witzke O, Arns W, Lehner F, Guba M, Jacobi J, Kliem V, Reinke P, Hauser IA, Vogt B, Stahl R, Rath T, Duerr M, Paulus EM, May C, Porstner M, Sommerer C; HERAKLES Study Group. Everolimus with cyclosporine withdrawal or low-exposure cyclosporine in kidney transplantation from Month 3: a multicentre, randomized trial. Nephrol Dial Transplant. 2017 Jun 1;32(6):1060-1070. doi: 10.1093/ndt/gfx075.

Reference Type: DERIVED

PMID: 28605781 (View on PubMed)

Other Identifiers

2006-007021-32

Identifier Type: -

Identifier Source: secondary_id

CRAD001ADE13

Identifier Type: -

Identifier Source: org_study_id