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

Novartis Pharmaceuticals802 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

802

Conditions

Kidney Transplantation

Interventions

EverolimusDRUG

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

MyforticDRUG

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 OptoralDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (18)

Novartis Investigative Site

Aachen, Germany

Novartis Investigative Site

Berlin, Germany

Outcomes

Primary Outcomes

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

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

Secondary Outcomes

GFR Via Nankivell Formula at Month 12 - All Regimens

Change 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.

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

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

Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat: For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), 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.

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

Data from ClinicalTrials.gov

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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

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

...and 8 more locations

GFR at Month 12 Utilizing Cockcroft-Gault Formula

Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

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

Mean Change in Serum Creatinine From Month 3 to Month 12

Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

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

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

Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).

Time frame: From Baseline 2 (Month 3) to Month 6

Efficacy Event Data Baseline 2 (Month 3) to Month 12

Time frame: From Baseline 2 (Month 3) to Month 12

Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk)

The Framingham Score (based on LDL cholesterol level) estimates the coronary heart disease risk (%) of developing one of the following coronary heart diseases: angina pectoris, myocardial infarction, or coronary disease death, over the course of 10 years.

Time frame: From Baseline 2 (Month 3) to Month 12

GFR Calculated Via Nankivell Formula at Month 60

Time frame: From randomization at BL2 (Month 3) to Month 60

GFR at Month 60 Utilizing Cockcroft-Gault Formula

Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl) For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

Time frame: From randomization at BL2 (Month 3) to Month 60 post-transplant

GFR at Month 60 Utilizing Modification of Diet in Renal Disease (MDRD) Method

Time frame: From randomization at BL2 (Month 3) to Month 60 post-transplant

Mean Change in Serum Creatinine From Month 3 to Month 60

Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

Time frame: From randomization at BL2 (Month 3) to Month 60 post-transplant

Efficacy Event Data After Month 12 to Month 60

Time frame: Events starting after Month 12