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

Phase 4

• Conditions: De Novo Transplant Disease
• Interventions: Drug: Tacrolimus targeted half-dose; Drug: Tacrolimus targeted plain dose

• Registration Number: NCT01744470
• Lead Sponsor: University Hospital, Tours

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05
• Study First Submitted: 2012-06-11
• Study First Submitted QC: 2012-12-05
• Study First Posted: 2012-12-06
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-07
• Last Update Posted: 2014-04-08
• Primary Completion: 2015-03
• Study Completion: 2015-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 286

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A - tacrolimus half-dose	Tacrolimus targeted half-dose	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
Group B - tacrolimus unchanged dose	Tacrolimus targeted plain dose	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

Primary Outcome Measures

Name	Time	Method
Renal function at one year post transplantation	12 months	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.

Secondary Outcome Measures

Name	Time	Method
To determine and compare according to randomized group	12 months	Overall safety assessment

Trial Locations

Locations (16)

Hôpital Pontchaillou; 🇫🇷 Rennes, France

CHU de Toulouse; 🇫🇷 Toulouse, France

Hôpital Sud; 🇫🇷 Amiens, France

Hôpital Bois-Guillaume; 🇫🇷 Bois-Guillaume, France

Hôpital Necker; 🇫🇷 Paris, France

CHU de Angers; 🇫🇷 Angers, France

Hôpital Cavale Blanche; 🇫🇷 Brest, France

CHU de Caen; 🇫🇷 Caen, France

Hôpital Gabriel Montpied; 🇫🇷 Clermont-Ferrand, France

Hôpital Dupuytren; 🇫🇷 Limoges, France

Hôpital Maison Blanche; 🇫🇷 Reims, France

HEGP; 🇫🇷 Paris, France

Hôpital Civil; 🇫🇷 Strasbourg, France

CHRU de Tours; 🇫🇷 Tours, France

Hôpital Bicêtre; 🇫🇷 Le Kremlin Bicêtre, France

Hôpital Archet II; 🇫🇷 Nice, France