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

Regional University Hospital Center (CHRU)

Status and phase: Unknown; Phase 4

Conditions: De Novo Transplant Disease

Treatments: Drug: Tacrolimus targeted half-dose; Drug: Tacrolimus targeted plain dose

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01744470

2011-003184-29 (EudraCT Number)

PHAO2011/YL/ADEQUATE

Details and patient eligibility

About

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).

Enrollment: 286 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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286 participants in 2 patient groups

Group A - tacrolimus half-dose

Experimental group

Description:

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

Treatment:

Drug: Tacrolimus targeted half-dose

Group B - tacrolimus unchanged dose

Experimental group

Description:

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

Treatment:

Drug: Tacrolimus targeted plain dose