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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
University Hospital, Tours
ClinicalTrials.gov Identifier:
NCT01744470
First received: June 11, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
De Novo Transplant Disease
Drug: Tacrolimus targeted half-dose
Drug: Tacrolimus targeted plain dose
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:
  • Renal function at one year post transplantation [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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:
  • To determine and compare according to randomized group [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Routine graft histology at M12 assessed using Banff 2009 classification, with specific analysis of interstitial fibrosis (IF) using numeric quantification

  • To determine and compare according to randomized group [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Glucose metabolism at M4 and M12

  • To determine and compare according to randomized group [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Infection rate including BKV and CMV at M4 and M12

  • To determine and compare according to randomized group [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Presence and intensity of Donor Specific Antibody (DSA) at M3 and M12

  • To determine and compare according to randomized group [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of biopsy proven acute rejection episode at M12

  • To determine and compare according to randomized group [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Graft and patient survival at M12

  • To determine and compare according to randomized group [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Overall safety assessment


Enrollment: 286
Study Start Date: May 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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

Drug: Tacrolimus targeted half-dose
Other Name: Advagraf®
Experimental: 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
Drug: Tacrolimus targeted plain dose
Other Name: Advagraf®

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01744470

Locations
France
Hôpital Sud
Amiens, France
CHU de Angers
Angers, France
Hôpital Bois-Guillaume
Bois-Guillaume, France, 76130
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, 75015
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
Sponsors and Collaborators
University Hospital, Tours
Astellas Pharma Inc
Investigators
Principal Investigator: Yvon LEBRANCHU University Hospital, Tours
  More Information

No publications provided

Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT01744470     History of Changes
Other Study ID Numbers: PHAO2011/YL/ADEQUATE, 2011-003184-29
Study First Received: June 11, 2012
Last Updated: April 7, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by University Hospital, Tours:
Renal
Transplantation
Tacrolimus

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014