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

NCT00514514 | Completed Phase 3 Results

• 2 other identifiers: CRAD001ADE132006-007021-32
• Study Type: interventional
• Target: 802
• Locations: 2 countries
• Sites: 18

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

Keywords

Everolimus; mycophenolate; CNI-free; kidney transplantation

Outcome Measures

Primary Outcomes (1)

• GFR Via Nankivell Method at Month 12 - CNI-Free vs Standard Regimen

  Demonstrate superiority of CNI-Free vs Standard Regimen in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. P-values are not adjusted

  From randomization at BL2 (Month 3) to Month 12 post-transplant

Secondary Outcomes (12)

• GFR Via Nankivell Formula at Month 12 - All Regimens

  From randomization at BL2 (Month 3) to Month 12 post-transplant

• GFR at Month 12 Utilizing Modification of Diet in Renal Disease (MDRD) Method

  From randomization at BL2 (Month 3) to Month 12 post-transplant

• GFR at Month 12 Utilizing Cockcroft-Gault Formula

  From randomization at BL2 (Month 3) to Month 12 post-transplant

• Mean Change in Serum Creatinine From Month 3 to Month 12

  From randomization at BL2 (Month 3) to Month 12 post-transplant

• Efficacy Event Data From Baseline 2 (Month 3) to Month 6

  From Baseline 2 (Month 3) to Month 6

Study Arms (3)

CNI standard regimen

ACTIVE COMPARATOR

Myfortic, Sandimmun Optoral and corticosteroids

Drug: Myfortic; Drug: Sandimmun Optoral; Drug: Simulect®

CNI free regimen

EXPERIMENTAL

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

Drug: Everolimus; Drug: Myfortic; Drug: Sandimmun Optoral

CNI low regimen

ACTIVE COMPARATOR

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

Drug: Everolimus; Drug: Sandimmun Optoral

Interventions

Everolimus 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

Also known as: Certican

CNI free regimen; CNI low regimen

Myfortic 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)

Also known as: Enteric Coated Mycophenolate Sodium

CNI free regimen; CNI standard regimen

Sandimmun Optoral DRUG

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

Also known as: Cyclosporine A

CNI free regimen; CNI low regimen; CNI standard regimen

Simulect® 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

Also known as: Basiliximab

CNI standard regimen

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Novartis Investigative Site

Aachen, 52074, Germany

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Cologne, 51109, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Essen, 45122, Germany

Location

Novartis Investigative Site

Frankfurt am Main, 60596, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Hannover Muenden, 34346, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Kaiserslautern, 67655, Germany

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Regensburg, 93053, Germany

Location

Novartis Investigative Site

Bern, 3010, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 30231851 DERIVED

• 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.

  PMID: 28605781 DERIVED

MeSH Terms

Interventions

Everolimus; Mycophenolic Acid; Cyclosporine; Basiliximab

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis

  Novartis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2007
• First Posted: August 10, 2007
• Study Start: July 1, 2007
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 18, 2017
• Results First Posted: January 18, 2017

Record last verified: 2016-11

Locations

DE (17); CH (1)