Clinical trial NCT00514514: Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a Calcineurin Inhibitor (CNI)-Free Regimen and a CNI-low Dose Regimen
Official title: Multi-center, Open-label, Prospective, Randomized, Parallel Group, Long-term Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a CNI-free Regimen and a CNI-low Dose Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Transplantation
Keywords: Everolimus
mycophenolate
CNI-free
kidney transplantation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-08-10
Enrollment: 802
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 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.


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)
* Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: GFR Via Nankivell Method at Month 12 - CNI-Free vs Standard Regimen
timeFrame: From randomization at BL2 (Month 3) to Month 12 post-transplant
Secondary outcomes:
measure: GFR Via Nankivell Formula at Month 12 - All Regimens
timeFrame: From randomization at BL2 (Month 3) to Month 12 post-transplant
measure: GFR at Month 12 Utilizing Modification of Diet in Renal Disease (MDRD) Method
timeFrame: From randomization at BL2 (Month 3) to Month 12 post-transplant
measure: GFR at Month 12 Utilizing Cockcroft-Gault Formula
timeFrame: From randomization at BL2 (Month 3) to Month 12 post-transplant
measure: Mean Change in Serum Creatinine From Month 3 to Month 12
timeFrame: From randomization at BL2 (Month 3) to Month 12 post-transplant
measure: Efficacy Event Data From Baseline 2 (Month 3) to Month 6
timeFrame: From Baseline 2 (Month 3) to Month 6
measure: Efficacy Event Data Baseline 2 (Month 3) to Month 12
timeFrame: From Baseline 2 (Month 3) to Month 12
measure: Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk)
timeFrame: From Baseline 2 (Month 3) to Month 12
measure: GFR Calculated Via Nankivell Formula at Month 60
timeFrame: From randomization at BL2 (Month 3) to Month 60
measure: GFR at Month 60 Utilizing Cockcroft-Gault Formula
timeFrame: From randomization at BL2 (Month 3) to Month 60 post-transplant
measure: GFR at Month 60 Utilizing Modification of Diet in Renal Disease (MDRD) Method
timeFrame: From randomization at BL2 (Month 3) to Month 60 post-transplant
measure: Mean Change in Serum Creatinine From Month 3 to Month 60
timeFrame: From randomization at BL2 (Month 3) to Month 60 post-transplant
measure: Efficacy Event Data After Month 12 to Month 60
timeFrame: Events starting after Month 12
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover Muenden
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Kaiserslautern
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Lubeck
country: Germany
facility: Novartis Investigative Site
city: Munchen
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
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: 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.