Prospective Study to Measure Vascular Parameters (Ancillary Study of ADEQUATE)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare parallel-group effects between 4 months and 12 months post-transplantation 2 values of target residual concentrations of Advagraf on vascular parameters in de novo renal transplant patients.

Official Title
-----------------
Effect of Advagraf on Arterial Stiffness and on Vascular Fibrosis Plasma Markers on de Novo Renal Transplant Patients

Conditions
-----------------
De Novo Transplant Disease

Intervention / Treatment
-----------------
* Drug: Tacrolimus targeted half-dose
* Drug: Tacrolimus targeted plain dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 et 70 years Patient accepting to give a written informed consent Recipients of a first renal allograft (deceased or living, non HLA identical donor with compatible ABO blood type) Randomized in the ADEQUATE study Patients must have at J112 +/- 3 days a stable renal function (MDRD 4) with an absence of DSA since transplantation. Negative T cross-match in cytotoxicity Tolerate a daily dose of MMF at 1g Exclusion Criteria: Acute rejection during the first months Existence of a BK infection since M3 Proteinuria/reatininuria ratio > 1g/g since M3

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A - tacrolimus half-dose<br>Immunosuppressive strategy with 50 % reduction of Advagraf® daily dose at M4 (randomization) and unchanged MMF dose. Targeted tacrolimus trough level are to be higher than 3 ng/mL . If the dose is not in adequation with the dispensable units, the prescribed dose will be the closest higher dose. Drug: Tacrolimus targeted half-dose | Drug: Tacrolimus targeted half-dose<br> <br> * Other names: Advagraf®;|
| Experimental: Group B - tacrolimus unchanged dose<br>Immunosuppressive strategy will remain identical after randomization (M4): unchanged Advagraf® and MMF doses. Targeted tacrolimus trough level are to be between 7 and 12 ng/mL Drug: Tacrolimus targeted plain dose | Drug: Tacrolimus targeted plain dose<br> <br> * Other names: Advagraf®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aorta stiffness at one year post-tranplantation | Evaluate the aorta stiffness at 1 year post-renal transplantation and its evolution in patients who received a half reduction of their daily dose of Advagraf ® 4 months after transplantation compared with patients whose dose has not been divided. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Evaluate peripheral and central blood pressures, the impact of reflected pressure waves and coupling cardiocirculatory (on the functional plan) and evaluate endothelial activation, factors promoting the vascular fibrosis and oxidant stress level (on biological plan) at 1 year post-renal transplantation and their evolution in patients who received a hal reduction of their daily dose Advagraf ® to four months of the transplant when compared with patients whose dose was not divided. | 12 months | 
| Endothelial activation at one year post-tranplantation | Evaluate peripheral and central blood pressures, the impact of reflected pressure waves and coupling cardiocirculatory (on the functional plan) and evaluate endothelial activation, factors promoting the vascular fibrosis and oxidant stress level (on biological plan) at 1 year post-renal transplantation and their evolution in patients who received a hal reduction of their daily dose Advagraf ® to four months of the transplant when compared with patients whose dose was not divided. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal, Transplantation, Tacrolimus, Arterial stiffness, Vascular fibrose plasma markers