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Absence of Steroid in Renal Transplantation and Digital Fibrosis Observation (Astronef)

Primary Purpose

Renal Transplant

Status

Completed

Phase

Phase 4

Locations

France

Study Type

Interventional

Intervention

Absence of corticotherapy post-transplantation

Corticotherapy post-transplantation

About this trial

This is an interventional treatment trial for Renal Transplant focused on measuring Corticotherapy, Fibrosis, Numerical reading, 18-70 years, first renal transplant was lost due to rejection, first or second renal transplant

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Absence of corticotherapy post-transplantation

Corticotherapy post-transplantation

Arm Description

All patients included in this arm will receive the usual treatment strategy (including Advagraf, Cellcept ou Myfortic and Simulect) without 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

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).

Average glomerular filtration rate

The average glomerular filtration rate, calculated by the MDRD formula (four variables, Modification Diet in Renal Disease).

Dialysis session

The percentage of patients with at least one dialysis session realised during the first year of transplant.

Ratio of proteinuria/creatinuria

Average of ratio of proteinuria/creatininuria (mg / mmol).

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).

Diagnosis of DSA

The percentage of patients with a diagnosis of DSA (Luminex® method) at 3 months and 1 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).

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.

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.

Full Information

NCT ID

NCT01541176

First Posted

February 23, 2012

Last Updated

January 30, 2019

Sponsor

Nantes University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01541176

Brief Title

Absence of Steroid in Renal Transplantation and Digital Fibrosis Observation

Acronym

Astronef

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

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

April 2012 (Actual)

Primary Completion Date

August 2018 (Actual)

Study Completion Date

August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Nantes University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Transplant

Keywords

Corticotherapy, Fibrosis, Numerical reading, 18-70 years, first renal transplant was lost due to rejection, first or second renal transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

193 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Absence of corticotherapy post-transplantation

Arm Type

Experimental

Arm Description

All patients included in this arm will receive the usual treatment strategy (including Advagraf, Cellcept ou Myfortic and Simulect) without corticotherapy post-transplantation.

Arm Title

Corticotherapy post-transplantation

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

Absence of corticotherapy post-transplantation

Intervention Description

No study treatment

Intervention Type

Drug

Intervention Name(s)

Corticotherapy post-transplantation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Percentage of fibrosis of the graft

Description

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.

Time Frame

One year post-transplantation

Secondary Outcome Measure Information:

Title

Percentage of fibrosis of the graft

Description

Time Frame

One year post-transplantation

Title

Percentage of fibrosis of the graft.

Description

Time Frame

One year post-transplantation

Title

Average glomerular filtration rate

Description

The average glomerular filtration rate, calculated by the MDRD formula (four variables, Modification Diet in Renal Disease).

Time Frame

One year post-transplantation

Title

Dialysis session

Description

The percentage of patients with at least one dialysis session realised during the first year of transplant.

Time Frame

One year post-transplantation

Title

Ratio of proteinuria/creatinuria

Description

Average of ratio of proteinuria/creatininuria (mg / mmol).

Time Frame

One year post-transplantation

Title

Episode of acute rejection

Description

Time Frame

One year post-transplantation

Title

Diagnosis of DSA

Description

The percentage of patients with a diagnosis of DSA (Luminex® method) at 3 months and 1 year post-transplantation.

Time Frame

One year post-transplantation

Title

Percentage of graft failure

Description

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).

Time Frame

One year post-transplantation

Title

Difference between numerical reading of fibrosis and evaluation by anatomical pathologists

Description

Time Frame

One year post-transplantation

Title

Number of adverse events

Description

Time Frame

One year post-transplantation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Overall Study Officials: