Clinical trial NCT01744470: Efficacy and Safety Study of a 4-Month Post-Renal Transplant Dose Reduction of Tacrolimus(ADEQUATE)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: De Novo Transplant Disease
Keywords: Renal
Transplantation
Tacrolimus
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
Collaborators: name: Astellas Pharma Inc
First posted: 2012-12-06
Enrollment: 286
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Renal function at one year post transplantation
timeFrame: 12 months
Secondary outcomes:
measure: To determine and compare according to randomized group
timeFrame: 12 months
measure: To determine and compare according to randomized group
timeFrame: 12 months
measure: To determine and compare according to randomized group
timeFrame: 12 months
measure: To determine and compare according to randomized group
timeFrame: 12 months
measure: To determine and compare according to randomized group
timeFrame: 12 months
measure: To determine and compare according to randomized group
timeFrame: 12 months
measure: To determine and compare according to randomized group
timeFrame: 12 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Hôpital Sud
city: Angers
country: France
facility: CHU de Angers
city: Bois-Guillaume
country: France
facility: Hôpital Bois-Guillaume
city: Brest
country: France
facility: Hôpital Cavale Blanche
city: Caen
country: France
facility: CHU de Caen
city: Clermont-Ferrand
country: France
facility: Hôpital Gabriel Montpied
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre
city: Limoges
country: France
facility: Hôpital Dupuytren
city: Nice
country: France
facility: Hôpital Archet II
city: Paris
country: France
facility: HEGP
city: Paris
country: France
facility: Hôpital Necker
city: Reims
country: France
facility: Hôpital Maison Blanche
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Strasbourg
country: France
facility: Hôpital Civil
city: Toulouse
country: France
facility: CHU de Toulouse
city: Tours
country: France
facility: CHRU de Tours
Study officials:
affiliation: University Hospital, Tours
name: Yvon LEBRANCHU
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.