Efficacy and Safety Study of a 4-Month Post-Renal Transplant Dose Reduction of Tacrolimus(ADEQUATE)

Study Overview
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Brief Summary
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This prospective, interventional, open label, randomized, multicenter study was designed to determine the risk/benefit ratio of a 50 % reduction of Advagraf® daily dose, 4 months after transplantation. Randomized patients are to be stable with their tacrolimus daily dose required to reach targeted tacrolimus trough levels. Based on Month-3 eligibility assessments, patients will be randomized in two groups (1:1): patients with 50 % reduction of the daily dose of Advagraf® 4 months after transplantation, and patients kept on their usual dose. The benefit/risk ratio will include the assessment of renal function, histological lesions from both alloreactivity and CNI nephrotoxicity, and safety data (metabolic and infectious diseases).

Official Title
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Efficacy and Safety Outcome of Two Different Targets of Advagraf® Trough Levels Between 4 Months and 12 Months After Transplantation Among de Novo Renal Transplant Recipients.

Conditions
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De Novo Transplant Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 et 70 years Patient accepting to give a written informed consent Recipients of a first renal allograft Cadaver or living transplantation or living (non HLA identical) donor with compatible ABO blood type. Absence of positive DSA using Luminex®, MFI>1,000 Negative cross-match in cytotoxicity Patient without difficulty to understand and communicate with the investigator and his collaborators Patient entitled to Health System benefits or other such benefits. Exclusion Criteria: Multiple organ transplantation Recipients of a dual kidney transplant Previous renal allograft History of any other transplantation Receiving a graft from a non-heart-beating donor Patient BMI > 35 Patients with evidence of severe liver disease, including abnormal liver profile (AST, ALT, or total bilirubin > 3 times upper limit of normal) at screening. Significant severe infection, active peptic ulcer and/or difficulty to absorb oral drugs (active upper gastro-intestinal tract malabsorption syndrome) HIV-positive patients, or with an active B or C hepatitis Patients with de novo malignancy prior to transplantation, other than efficiently treated basal or squamous cell carcinoma of the skin. Leucocyte count lower than 2500/mm3 Female patients who are pregnant, lactating or of child bearing potential and not practicing an approved method of birth control. Known allergy or intolerance to basiliximab, tacrolimus, macrolide antibiotics, corticosteroids, or mycophenolate mofetil or any of the product excipients Participation in a clinical trial or expanded access trial with an investigational drug within 4 weeks prior to enrollment or concomitantly with this study Any clinical condition which, in the opinion of the investigator, would not allow safe completion of the study

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function at one year post transplantation | Renal function at one year post transplantation estimated by the glomerular filtration rate (GFR) using MDRD 4 (Modification Diet in Renal Disease). Crude difference in renal function at one year between groups and the change of renal function between 4 months and one year in each group will be analyzed and compared. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine and compare according to randomized group | Routine graft histology at M12 assessed using Banff 2009 classification, with specific analysis of interstitial fibrosis (IF) using numeric quantification | 12 months | 
| To determine and compare according to randomized group | Glucose metabolism at M4 and M12 | 12 months | 
| To determine and compare according to randomized group | Infection rate including BKV and CMV at M4 and M12 | 12 months | 
| To determine and compare according to randomized group | Presence and intensity of Donor Specific Antibody (DSA) at M3 and M12 | 12 months | 
| To determine and compare according to randomized group | Incidence of biopsy proven acute rejection episode at M12 | 12 months | 
| To determine and compare according to randomized group | Graft and patient survival at M12 | 12 months | 
| To determine and compare according to randomized group | Overall safety assessment | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal, Transplantation, Tacrolimus