Clinical trial NCT01541176: Absence of Steroid in Renal Transplantation and Digital Fibrosis Observation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplant
Keywords: Corticotherapy
Fibrosis
Numerical reading
18-70 years
first renal transplant was lost due to rejection
first or second renal transplant
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2012-02-29
Enrollment: 193
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 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).


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.

Primary outcomes:
measure: Percentage of fibrosis of the graft
timeFrame: One year post-transplantation
Secondary outcomes:
measure: Percentage of fibrosis of the graft
timeFrame: One year post-transplantation
measure: Percentage of fibrosis of the graft.
timeFrame: One year post-transplantation
measure: Average glomerular filtration rate
timeFrame: One year post-transplantation
measure: Dialysis session
timeFrame: One year post-transplantation
measure: Ratio of proteinuria/creatinuria
timeFrame: One year post-transplantation
measure: Episode of acute rejection
timeFrame: One year post-transplantation
measure: Diagnosis of DSA
timeFrame: One year post-transplantation
measure: Percentage of graft failure
timeFrame: One year post-transplantation
measure: Difference between numerical reading of fibrosis and evaluation by anatomical pathologists
timeFrame: One year post-transplantation
measure: Number of adverse events
timeFrame: One year post-transplantation
Other outcomes:
Locations:
city: Lyon
country: France
facility: CHU de Lyon
city: Nantes
country: France
facility: Nantes University Hospital
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: AP-HP - Hôpital Necker
city: Paris
country: France
facility: AP-HP - Hôpital Bicêtre
city: Saint-Etienne
country: France
facility: CHU de Saint-Etienne
city: Toulouse
country: France
facility: CHU de Toulouse
city: Tours
country: France
facility: CHRU de Tours
Study officials:
affiliation: Nantes University Hospital
name: Diego CANTAROVICH, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Toulouse
name: Lionel ROSTAING, Profesor
role: STUDY_CHAIR
affiliation: Hôpital Necker (AP-HP)
name: Christophe LEGENDRE, Profesor
role: STUDY_CHAIR
affiliation: Hospices Civils de Lyon
name: Emmanuel MORELON, Profesor
role: STUDY_CHAIR
affiliation: Centre Hospitalier Universitaire de Nice
name: Elisabeth CASSUTO-VIGUIER, Doctor
role: STUDY_CHAIR
affiliation: CHU de Saint-Etienne
name: Christophe MARIAT, Profesor
role: STUDY_CHAIR
affiliation: CHRU de Tours
name: Matthias BÜCHLER, Profesor
role: STUDY_CHAIR
affiliation: Hôpital Bicêtre (AP-HP)
name: Antoine DURRBACH, Profesor
role: STUDY_CHAIR
References: