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

De Novo Transplant Disease Clinical Trial

— 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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01744470
• Other study ID #: PHAO2011/YL/ADEQUATE
• Secondary ID: 2011-003184-29
• Status: Active, not recruiting
• Phase: Phase 4
• First received: June 11, 2012
• Last updated: April 7, 2014
• Start date: May 2012
• Est. completion date: March 2015

Study information

• Verified date: April 2014
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 286
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• De Novo Transplant Disease

Intervention

Drug:
• Tacrolimus targeted half-dose

• Tacrolimus targeted plain dose

Locations

Country	Name	City	State
France	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

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Tours	Astellas Pharma Inc

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	To determine and compare according to randomized group	Glucose metabolism at M4 and M12	12 months	Yes
Secondary	To determine and compare according to randomized group	Infection rate including BKV and CMV at M4 and M12	12 months	Yes
Secondary	To determine and compare according to randomized group	Presence and intensity of Donor Specific Antibody (DSA) at M3 and M12	12 months	Yes
Secondary	To determine and compare according to randomized group	Incidence of biopsy proven acute rejection episode at M12	12 months	Yes
Secondary	To determine and compare according to randomized group	Graft and patient survival at M12	12 months	Yes
Secondary	To determine and compare according to randomized group	Overall safety assessment	12 months	Yes