Absence of Steroid in Renal Transplantation and Digital Fibrosis Observation

Study Overview
=================
Brief Summary
-----------------
The main objective of this study is to demonstrate that the absence of post-transplantation corticosteroids does not induce a larger increase of renal graft fibrosis (by numerical reading) on biopsy at one year post-transplantation than immunosuppressive treatment strategy that includes standard oral corticosteroids.The secondary objectives of the study consist to compare on various parameters (fibrosis progression, renal function, dialysis, ratio of proteinuria/creatinuria, acute rejection, donor-specific antibody, graft survival, clinical and biological tolerance) therapy with no corticosteroids post-transplantation in comparison to standard immunosuppressive treatment strategies including oral corticosteroids. Secondary objectives of the study consist also to compare the two techniques for assessing fibrosis by numerical reading and by centralized blinded reading of the treatment group (by 2 anatomical pathologists).

Official Title
-----------------
Impact of the Absence of Steroids on the Evolution of Renal Function and on the Progression of Graft Fibrosis, Quantified by Numerical Method, in Patients With Renal Transplant

Conditions
-----------------
Renal Transplant

Intervention / Treatment
-----------------
* Other: Absence of corticotherapy post-transplantation
* Drug: Corticotherapy post-transplantation


Participation Criteria
=================
Eligibility Criteria
-----------------
Pre-Inclusion Criteria: Adults aged 18 to70 years, Accepting to give, after information, their signed informed consent form, Not having difficulties to understand and communicate with the investigator and his representatives, Requiring a renal transplant [first or second transplant (except if the first renal transplant was lost due to rejection)], Patient insured. Inclusion criteria : Transplant of a kidney from a deceased or living donor (non HLA-identical) with ABO compatibility, Existence of a renal graft biopsy (or of one of the grafts, if bi-renal transplant) before transplantation, Percentage of positive responses to PRA (panel reactive antibodies), measured by the Luminex® less than 20% of IgG anti-T or absence of positive DSA by Luminex regardless of the mean fluorescence (MFI) within the last 6 months, Negative cross match T in cytotoxicity and / or flow cytometry, Negative pregnancy test for patients of childbearing age, and consent to use an effective contraception throughout the study and 6 weeks after the end of the study. Exclusion Criteria: First renal transplant lost due to rejection, Combined transplantation, Previous history of transplantation other than kidney, Non beating donor heart, Presence of positive DSA by Luminex® regardless of the average of fluorescence (MFI), Patients receiving corticosteroids at the time of transplantation, Necessity to continue administration of systemic immunosuppressive treatment before transplantation, Infections or severe diarrhea, vomiting, upper gastrointestinal tract malabsorption or active peptic ulcers, concomitant, significant and uncontrolled, Subject or HIV positive donor, Replicating viral hepatitis at the time of randomization, Known allergy or intolerance to tacrolimus, macrolide, corticosteroids, mycophenolate mofetil or to any of the excipients, Diagnosis of de novo malignancy prior to transplantation, with the exception of treated effectively basal cell or squamous cell carcinomas of the skin,- Current participation at another clinical study, All clinical condition that the investigator considers incompatible with the conduct of the study in acceptable security conditions, Inability of patient to comply with study procedures, Pregnant or breast-feeding women, Person placed under guardianship, under protection of law.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Absence of corticotherapy post-transplantation<br>All patients included in this arm will receive the usual treatment strategy (including Advagraf, Cellcept ou Myfortic and Simulect) without corticotherapy post-transplantation. | Other: Absence of corticotherapy post-transplantation<br>* No study treatment<br>|
| Active Comparator: Corticotherapy post-transplantation<br>All patients included in this arm will receive the usual treatment strategy (including Advagraf, Cellcept ou Myfortic and Simulect) with corticotherapy post-transplantation : prednisone or prednisolone orally for at least one year post-transplantation. | Drug: Corticotherapy post-transplantation<br>* Prednisone or prednisolone orally for at least one year post-transplantation with the following minimal doses : D1 to D14 : 20 mg/day, D15 to M1 : 15 mg/day, M1 to M3 : 10 mg/day, M3 to M12 : 5 mg/day.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of fibrosis of the graft | Evolution of the percentage of fibrosis of the graft during the first year after transplantation (pre-transplant biopsy versus biopsy at one year), by numerical reading of fibrosis by image analysis. | One year post-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of fibrosis of the graft | Evolution of the percentage of fibrosis of the graft during the first year after transplantation (pre-transplant biopsy versus biopsy at one year of which the blinded readings to treatment group are made by two independent anatomical pathologists, the Banff criteria 2009). | One year post-transplantation | 
| Percentage of fibrosis of the graft. | The percentage of fibrosis of the graft at one year post-transplantation (biopsy at one year with numerical reading of fibrosis by image analysis and blinded reading to treatment group by two independent anatomical pathologists, the Banff criteria 2009). | One year post-transplantation | 
| Average glomerular filtration rate | The average glomerular filtration rate, calculated by the MDRD formula (four variables, Modification Diet in Renal Disease). | One year post-transplantation | 
| Dialysis session | The percentage of patients with at least one dialysis session realised during the first year of transplant. | One year post-transplantation | 
| Ratio of proteinuria/creatinuria | Average of ratio of proteinuria/creatininuria (mg / mmol). | One year post-transplantation | 
| Episode of acute rejection | The percentage of patients with at least one episode of acute rejection during the first year after transplantation. We will distinguish biopsy-proven acute rejection (RABP), the corticosteroids resistant RABP and severe RABP (Banff 2009). | One year post-transplantation | 
| Diagnosis of DSA | The percentage of patients with a diagnosis of DSA (Luminex® method) at 3 months and 1 year post-transplantation. | One year post-transplantation | 
| Percentage of graft failure | The percentage of graft failure (death or return to dialysis) during the first year of transplantation (the short duration of the study avoids the management of right censoring). | One year post-transplantation | 
| Difference between numerical reading of fibrosis and evaluation by anatomical pathologists | The difference between the percentage of graft fibrosis evaluated by numerical reading of fibrosis and that assessed by two independent anatomical pathologists (Banff 2009 criteria) at baseline, 3 months and 1 year post-transplantation. | One year post-transplantation | 
| Number of adverse events | Adverse events (AE) at 12 months post-transplantation, of which AEs of special interest (NODAT, dyslipidemia, hypertension, CMV viral infections, BKV) with an assessment of vital signs, physical examinations and laboratory tests. | One year post-transplantation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Corticotherapy, Fibrosis, Numerical reading, 18-70 years, first renal transplant was lost due to rejection, first or second renal transplant