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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01744470
Recruitment Status : Unknown
Verified April 2014 by University Hospital, Tours.
Recruitment status was:  Active, not recruiting
First Posted : December 6, 2012
Last Update Posted : April 8, 2014
Astellas Pharma Inc
Information provided by (Responsible Party):
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).

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 286 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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.
Study Start Date : May 2012
Estimated Primary Completion Date : March 2015
Estimated Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
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®

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

  2. To determine and compare according to randomized group [ Time Frame: 12 months ]
    Glucose metabolism at M4 and M12

  3. To determine and compare according to randomized group [ Time Frame: 12 months ]
    Infection rate including BKV and CMV at M4 and M12

  4. To determine and compare according to randomized group [ Time Frame: 12 months ]
    Presence and intensity of Donor Specific Antibody (DSA) at M3 and M12

  5. To determine and compare according to randomized group [ Time Frame: 12 months ]
    Incidence of biopsy proven acute rejection episode at M12

  6. To determine and compare according to randomized group [ Time Frame: 12 months ]
    Graft and patient survival at M12

  7. To determine and compare according to randomized group [ Time Frame: 12 months ]
    Overall safety assessment

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01744470

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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
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
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Principal Investigator: Yvon LEBRANCHU University Hospital, Tours
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University Hospital, Tours Identifier: NCT01744470    
Other Study ID Numbers: PHAO2011/YL/ADEQUATE
2011-003184-29 ( EudraCT Number )
First Posted: December 6, 2012    Key Record Dates
Last Update Posted: April 8, 2014
Last Verified: April 2014
Keywords provided by University Hospital, Tours:
Additional relevant MeSH terms:
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Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action