Protocol Calcineurin Inhibitor (CNI) Weaning

This study is currently recruiting participants. (see Contacts and Locations)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 October 19, 2014