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 - Full Text View

Purpose

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).

Condition	Intervention	Phase
Renal Transplant	Other: Absence of corticotherapy post-transplantation Drug: Corticotherapy post-transplantation	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation Steroids

U.S. FDA Resources

Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:

Percentage of fibrosis of the graft [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Percentage of fibrosis of the graft [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
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).
Percentage of fibrosis of the graft. [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
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).
Average glomerular filtration rate [ Designated as safety issue: No ]
The average glomerular filtration rate, calculated by the MDRD formula (four variables, Modification Diet in Renal Disease).
Dialysis session [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
The percentage of patients with at least one dialysis session realised during the first year of transplant.
Ratio of proteinuria/creatinuria [ Designated as safety issue: No ]
Average of ratio of proteinuria/creatininuria (mg / mmol).
Episode of acute rejection [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
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).
Diagnosis of DSA [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
The percentage of patients with a diagnosis of DSA (Luminex® method) at 3 months and 1 year post-transplantation.
Percentage of graft failure [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
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).
Difference between numerical reading of fibrosis and evaluation by anatomical pathologists [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
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.
Number of adverse events [ Time Frame: One year post-transplantation ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	186
Study Start Date:	April 2012
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	October 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Absence of corticotherapy post-transplantation 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 No study treatment
Active Comparator: Corticotherapy post-transplantation 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 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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01541176

Contacts

Contact: Diego CANTAROVICH, MD, PhD

02 40 08 74 40

diego.cantarovich@chu-nantes.fr

Locations

France
Nantes University Hospital	Recruiting
Nantes, France, 44093
Contact: Diego CANTAROVICH, MD, PhD 02 40 08 74 40 diego.cantarovich@chu-nantes.fr
Principal Investigator: Diego CANTAROVICH, MD, PhD

Sponsors and Collaborators

Nantes University Hospital

Investigators

Principal Investigator:	Diego CANTAROVICH, MD, PhD	CHU de Nantes
Study Chair:	Lionel ROSTAING, Profesor	University Hospital, Toulouse
Study Chair:	Christophe LEGENDRE, Profesor	Hôpital Necker (AP-HP)
Study Chair:	Emmanuel MORELON, Profesor	CHU de Lyon
Study Chair:	Elisabeth CASSUTO-VIGUIER, Doctor	CHU de Nice
Study Chair:	Christophe MARIAT, Profesor	CHU de Saint-Etienne

More Information

No publications provided

Responsible Party:	Nantes University Hospital
ClinicalTrials.gov Identifier:	NCT01541176 History of Changes
Other Study ID Numbers:	RC11_0013
Study First Received:	February 23, 2012
Last Updated:	May 14, 2013
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Nantes University Hospital:

Corticotherapy
Fibrosis
Numerical reading

18-70 years
first renal transplant was lost due to rejection
first or second renal transplant

ClinicalTrials.gov processed this record on June 18, 2013

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 (Astronef)