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

February 8, 2011
April 2, 2014
February 2011
October 2015   (final data collection date for primary outcome measure)
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).
Same as current
Complete list of historical versions of study NCT01292525 on ClinicalTrials.gov Archive Site
  • 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)
Same as current
Not Provided
Not Provided
 
Protocol Calcineurin Inhibitor (CNI) Weaning
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

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®).

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Function of Renal Transplant
  • 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®).
  • 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.
  • Active Comparator: Tacrolimus
    Intervention: Drug: Tacrolimus
  • Experimental: Withdrawal of Tacrolimus
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
106
October 2015
October 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact: Magali GIRAL, Profesor 02 40 08 74 10 magali.giral@chu-nantes.fr
France
 
NCT01292525
09/7-D, 2010-019574-33
Yes
Pr Magali GIRAL, Nantes University Hospital
Nantes University Hospital
Not Provided
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
Nantes University Hospital
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP