12 Month Athena Study: Everolimus vs. Standard Regimen in de Novo Kidney Transplant Patients

Phase 3

Completed

Conditions: Kidney Transplantation
Renal Transplantation

Interventions: Drug: Everolimus
Drug: Enteric Coated Mycophenolate Sodium (EC-MPS)
Drug: Tacrolimus
Drug: Cyclosporin A
Drug: Mycophenolate mofetil (MMF)
Drug: Corticosteroids
Drug: Simulect

Registration Number: NCT01843348

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study was designed to evaluate the renal function comparing Certican based immunosuppressive regimens with two different CNIs (Tacrolimus or Cyclosporin A) versus a standard treatment with Mycophenolic Acid and Tacrolimus in de novo renal transplant recipients.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 612

Inclusion Criteria

Patient who had received a primary or secondary kidney transplant
Patients who were willing and from whom written informed consent was obtained
kidney allograft with a cold ischemia time (CIT) < 30 hours
negative pregnancy test prior to study enrollment

Exclusion Criteria

--Multi-organ recipients

former Graft loss due to immunological reasons
Patients who received a kidney from a non-heart beating donor
A-B-0 incompatible transplants
a current Panel Reactive Antibody (PRA) level of > 20%
existing antibodies against the HLA-type of the receiving transplant
a known hypersensitivity/contraindication to any of the immunosuppressants
Use of other investigational drugs
Patients with thrombocytopenia (platelets < 100,000/mm³), with an absolute neutrophil count of < 2,000/mm³ or leucopenia (leucocytes < 3,000/mm³), or hemoglobin < 8 g/dL
significant mental illness
history of malignancy during the last five years
HIV positive
uncontrolled hypercholesterolemia or hypertriglyceridemia
drug or alcohol abuse
pregnant or breast feeding women

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAC+MPA	Enteric Coated Mycophenolate Sodium (EC-MPS)	-
TAC+MPA	Mycophenolate mofetil (MMF)	-
TAC+MPA	Corticosteroids	-
TAC+MPA	Simulect	-
TAC+Certican	Everolimus	-
TAC+Certican	Tacrolimus	-
TAC+Certican	Corticosteroids	-
TAC+Certican	Simulect	-
CycA+Certican	Corticosteroids	-
CycA+Certican	Simulect	-
TAC+MPA	Tacrolimus	-
CycA+Certican	Everolimus	-
CycA+Certican	Cyclosporin A	-

Primary Outcome Measures

Name	Time	Method
Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens	One year post transplant	To demonstrate non-inferiority in renal function assessed by glomerular filtration rate (Nankivell formula) in at least one of the Certican® treatment regimens compared to the standard regimen group at month 12 post-transplantation in renal transplant patients. Nankivell formula: GFR = 6.7/Scr + BW/4 - Surea/2 - 100/(height)² + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The eGFR is expressed in mL/min per 1.73m². If a patient was on dialysis at the time of urea or creatinine assessment, the eGFR was set to 0. Analysis set = per protocol set

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12	Month 12 post transplant	Combined endpoint included: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS)
Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant	Month 12 post transplant	Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method = GFR=141 x min(Scr/κ, 1)α x max(Scr/κ, 1)1.209 x 0.993Age x 1.018 \[if female\] x 1.159 \[if black\] where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is 0.329 for females and 0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant	Month 12 post transplant	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
Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant	Month 12 post transplant	Modification of Diet in Renal Disease (MDRD) = For men: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x (albumin0,318) For women: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x albumin0,318) x 0.762 with urea nitrogen = urea / 2.144. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
Percentage of Participants With Treatment Failure Endpoints at Month 12	Month 12 post transplant	Treatment failure endpoints: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS)
Percent of Participants With Delayed Graft Function and Slow Graft Function	Post transplant to month 12	Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. Slow graft function (SGF) was defined as a serum creatinine \>3.0 mg/dL at Day 5 post-transplantation. Full analysis set
Percent of Participants With Delayed Graft Function by Day	Post transplant up to day 7	Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day.
Percent of Participants With Viral Infections	Post transplant to month 12	Viral infections for BKV Virus Humane Polyomavirus 1 and Cytomegalovirus
Percent of Participants With Wound Healing Complications During Study	Post transplant until individual reporting	Information collected to report wound healing process which included percentage of participants with complications, fluid collections detected and occurrence of lymphoceles
Duration of Wound Healing	Post transplant until individual reporting	A wound will be considered healed if all the suture material and staples are removed and the wound is intact. Number of participants is based on all patients of the respective treatment group in the safety set, excluding patients with no answer (unknown).