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

NCT ID: NCT01744470

Last Updated: 2014-04-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 286 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2015-03-31

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).

Conditions

De Novo Transplant Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A - tacrolimus 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 Type: EXPERIMENTAL

Tacrolimus targeted half-dose

Intervention Type: DRUG

Group B - tacrolimus unchanged 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

Group Type: EXPERIMENTAL

Tacrolimus targeted plain dose

Intervention Type: DRUG

Interventions

Tacrolimus targeted half-dose

Intervention Type: DRUG

Tacrolimus targeted plain dose

Intervention Type: DRUG

Other Intervention Names

Advagraf®; Advagraf®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

University Hospital, Tours

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yvon LEBRANCHU

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Tours

Locations

Hôpital Sud

Amiens, , France

CHU de Angers

Angers, , France

Hôpital Bois-Guillaume

Bois-Guillaume, , France

Hôpital Cavale Blanche

Brest, , France

CHU de Caen

Caen, , France

Hôpital Gabriel Montpied

Clermont-Ferrand, , France

Hôpital Bicêtre

Le Kremlin-Bicêtre, , France

Hôpital Dupuytren

Limoges, , France

Hôpital Archet II

Nice, , France

HEGP

Paris, , France

Hôpital Necker

Paris, , France

Hôpital Maison Blanche

Reims, , France

Hôpital Pontchaillou

Rennes, , France

Hôpital Civil

Strasbourg, , France

CHU de Toulouse

Toulouse, , France

CHRU de Tours

Tours, , France

Countries

France

References

Gatault P, Kamar N, Buchler M, Colosio C, Bertrand D, Durrbach A, Albano L, Rivalan J, Le Meur Y, Essig M, Bouvier N, Legendre C, Moulin B, Heng AE, Weestel PF, Sayegh J, Charpentier B, Rostaing L, Thervet E, Lebranchu Y. Reduction of Extended-Release Tacrolimus Dose in Low-Immunological-Risk Kidney Transplant Recipients Increases Risk of Rejection and Appearance of Donor-Specific Antibodies: A Randomized Study. Am J Transplant. 2017 May;17(5):1370-1379. doi: 10.1111/ajt.14109. Epub 2017 Jan 3.

Reference Type: DERIVED

PMID: 27862923 (View on PubMed)

Other Identifiers

2011-003184-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PHAO2011/YL/ADEQUATE

Identifier Type: -

Identifier Source: org_study_id