Protocol Calcineurin Inhibitor (CNI) Weaning

This study is currently recruiting participants.
Verified April 2014 by Nantes University Hospital
Sponsor:
Information provided by:
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT01292525
First received: February 8, 2011
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

The main objective of this study is to demonstrate the benefit of the withdrawal of Tacrolimus (Prograf®) on renal function in patients one year after the end of the weaning period. The secondary objectives will focus on assessing the risks and consequences of withdrawal of Tacrolimus (Prograf®).


Condition Intervention Phase
Function of Renal Transplant
Drug: Tacrolimus
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective, Multicenter, Randomized, Double-blind, Controlled Parallel Group Study Designed to Assess the Risk-benefit Balance of the Gradual Withdrawal of a Calcineurin Inhibitor (Tacrolimus) in Renal Transplant Patients Over 4 Years and Clinically Selected

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • Renal function [ Time Frame: one year after complete withdrawal of Tacrolimus ] [ Designated as safety issue: Yes ]
    The primary endpoint will be the improvement of renal function one year after complete withdrawal of Tacrolimus (Prograf®) assessed by measuring the glomerular filtration rate (GFR) calculated by the dosage of cystatin C according to the equation Bricon. The DFG will be compared between times J-30 and J480 (1 year after the withdrawal).


Secondary Outcome Measures:
  • Renal function [ Time Frame: one year after complete withdrawal ] [ Designated as safety issue: Yes ]
    Improvement of renal function by measuring serum creatinine, using the original MDRD equation,

  • Acute rejection [ Time Frame: one year after complete withdrawal ] [ Designated as safety issue: No ]
    Rate of histologically proven acute rejection by biopsy according to Banff classification 2009,

  • Chronic rejection [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    Rate of chronic rejection histologically proven by biopsy according to Banff classification 2009,

  • Steroid-resistant rejection [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    Rates of steroid-resistant rejection

  • Graft survival [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    Rate of return to dialysis (graft survival)

  • Cancer and infections [ Time Frame: one year after complete withdrawal ] [ Designated as safety issue: No ]
    Incidence of cancer and infections

  • Patients survival [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    Survival rate of patients

  • Anti-HLA antibodies [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    Appearance of anti-HLA donor specific and non-donor specific antibodies measured by the technique Luminex

  • Histological lesions of rejection [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    The appearance of histological lesions of cellular or humoral acute or chronic or subclinical rejection on the biopsy protocol

  • Histological lesions of fibrosis [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    Onset or worsening of histological lesions of interstitial fibrosis and tubular atrophy on biopsy inflammatory

  • Hypertension, hyperglycemia and hyperlipidemia [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    Incidence of hypertension, hyperglycemia and hyperlipidemia

  • Quality of life [ Time Frame: One year after complete withdrawal ] [ Designated as safety issue: No ]
    Determination of the benefits of withdrawal of Tacrolimus on the quality of life of patients, defined by the scale of quality of life validated SF-36 used at the beginning (J-15) and at the end of the weaning period (J120) at 6 months (J300) and one year after complete withdrawal of Tacrolimus (J480)


Estimated Enrollment: 106
Study Start Date: February 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tacrolimus Drug: Tacrolimus
A control group continued conventional therapy, Tacrolimus (Prograf®) ("control" group) and will be followed in parallel group "withdrawal" that will stop treatment with Tacrolimus (Prograf®).
Experimental: Withdrawal of Tacrolimus Drug: Placebo
Patients randomized to the "withdrawal"group will begin the protocol with their usual dose of Tacrolimus (Prograf®) (initial dose). The initial dose of tacrolimus (Prograf®) will be reduced by one third at visit 3 (day 0) and again a third visit 5 (J60). The complete withdrawal Tacrolimus (Prograf®) begins to visit 7 (J120). The withdrawal of Tacrolimus (Prograf®) will be obtained in four months. Monitoring of all patients lasted 17 months in total from the screening visit, which corresponds to 12 months after complete withdrawal of Tacrolimus (Prograf®) for patients in the "withdrawal" group.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Pre-inclusion criteria :

  • Male or female aged between 18 and 80 years (inclusive),
  • Having received a deceased donor transplant or living with ABO compatibility,
  • First renal allograft for at least 4 years and under 10 years,
  • Presenting a stable renal function : serum creatinine with a variation of ± 25% of the average of the year before inclusion,
  • Treated with tacrolimus (Prograf®) in combination with MPA (Cellcept® and Myfortic®) + / - steroids (between 5 and 10 mg per day),
  • Patient has given informed consent,
  • Patient insured,
  • Patient (of childbearing age) with effective contraception.

Inclusion Criteria:

  • Glomerular Filtration Rate (GFR), defined by the dosage of cystatin C ≥ 40 ml/min/1, 73m²,
  • Proteinuria ≤ 0,5 g / day,
  • Patient with serum levels of Tacrolimus between 5 to 10 ng / ml on average during the last 6 months (inclusive). It is accepted that 25% of the assays performed during the last 6 months, serum levels of tacrolimus are outside the limits mentioned above (5-10 ng / ml). They must nevertheless be between 3.5 to 12.5 ng / ml (inclusive).
  • Patient with serum levels of MPA (Cellcept® and Myfortic®) higher ≥ 30 mg / ml,
  • No anti-HLA antibodies at the time of inclusion, verified using highly sensitive techniques (Luminex HD),
  • Lack of histological evidence of cellular or humoral acute or chronic or subclinical rejection on renal graft according to the latest classification of Banff 2009.

Exclusion Criteria:

  • Patients under age 18 or over 80 years,
  • Transplanted from less than 4 years and over 10 years,
  • Patients re-transplanted,
  • Transplantation of several organs,
  • Patient not treated with tacrolimus as maintenance therapy,
  • Serum levels of Tacrolimus patient <5 or >10 ng / ml,
  • Serum levels of MPA of the patient <30 mg / ml,
  • Patients treated with other immunosuppressive drugs that Tacrolimus (Prograf®), MPA (Cellcept® and Myfortic®) and steroids,
  • Patient not having a stable graft function at baseline (change in serum creatinine > 25% of the average of the year before inclusion in the study), with a GFR defined by the dosage of cystatin C <40 ml/min/1, 73m² at the time of inclusion,- Patients with proteinuria > 0.5 g at study entry,
  • Patient with HLA antibodies at study entry,
  • Patient non-compliant,
  • Presence of histological evidence of cellular or humoral acute or chronic or subclinical rejection on renal graft according to the latest classification of Banff 2009,
  • History of lymphoproliferative disorders,
  • Diagnosis of a malignancy within 5 years before enrollment,
  • Significantly abnormal hematologic data of a clinical standpoint, as determined by the investigator for hematocrit, hemoglobin, white blood cell count or platelets,
  • Data significantly abnormal blood biochemistry of a clinical standpoint, as determined by the investigator,
  • Abuse of significant drug or alcohol at the time of inclusion, determined by the investigator,
  • Patient positive for antibodies to hepatitis C or hepatitis B surface antigen of hepatitis B (HBsAg) or HIV infection,
  • Participation in a clinical study within 3 months,
  • Pregnancy, Breastfeeding.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01292525

Contacts
Contact: Magali GIRAL, Profesor 02 40 08 74 10 magali.giral@chu-nantes.fr

Locations
France
Nantes University Hospital Recruiting
Nantes, France, 44093
Contact: Magali GIRAL, Profesor    02 40 08 74 10      
Principal Investigator: Magali GIRAL, Profesor         
Sponsors and Collaborators
Nantes University Hospital
Investigators
Principal Investigator: Magali GIRAL, Profesor CHU de Nantes
Study Chair: Jean-Paul SOULILLOU, Profesor CHU de Nantes
Study Chair: Christophe LEGENDRE, Profesor Hôpital Necker - AP-HP
Study Chair: Emmanuel MORELON, Profesor CHU de Lyon
Study Chair: Georges MOURAD, Profesor CHU de Montpellier
  More Information

No publications provided

Responsible Party: Pr Magali GIRAL, Nantes University Hospital
ClinicalTrials.gov Identifier: NCT01292525     History of Changes
Other Study ID Numbers: 09/7-D, 2010-019574-33
Study First Received: February 8, 2011
Last Updated: April 2, 2014
Health Authority: France : AFSSAPS

Keywords provided by Nantes University Hospital:
Withdrawal of Tacrolimus and renal graft
renal allograft
stable renal function

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

ClinicalTrials.gov processed this record on April 17, 2014