Clinical trial NCT01292525: Protocol Calcineurin Inhibitor (CNI) Weaning
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Function of Renal Transplant
Keywords: Withdrawal of Tacrolimus and renal graft
renal allograft
stable renal function
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2011-02-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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®).


Eligibility 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.

Primary outcomes:
measure: Renal function
timeFrame: one year after complete withdrawal of Tacrolimus
Secondary outcomes:
measure: Renal function
timeFrame: one year after complete withdrawal
measure: Acute rejection
timeFrame: one year after complete withdrawal
measure: Chronic rejection
timeFrame: One year after complete withdrawal
measure: Steroid-resistant rejection
timeFrame: One year after complete withdrawal
measure: Graft survival
timeFrame: One year after complete withdrawal
measure: Cancer and infections
timeFrame: one year after complete withdrawal
measure: Patients survival
timeFrame: One year after complete withdrawal
measure: Anti-HLA antibodies
timeFrame: One year after complete withdrawal
measure: Histological lesions of rejection
timeFrame: One year after complete withdrawal
measure: Histological lesions of fibrosis
timeFrame: One year after complete withdrawal
measure: Hypertension, hyperglycemia and hyperlipidemia
timeFrame: One year after complete withdrawal
measure: Quality of life
timeFrame: One year after complete withdrawal
Other outcomes:
Locations:
city: Nantes
country: France
facility: Nantes University Hospital
Study officials:
affiliation: Nantes University Hospital
name: Magali GIRAL, Profesor
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes University Hospital
name: Jean-Paul SOULILLOU, Profesor
role: STUDY_CHAIR
affiliation: Hôpital Necker - AP-HP
name: Christophe LEGENDRE, Profesor
role: STUDY_CHAIR
affiliation: Hospices Civils de Lyon
name: Emmanuel MORELON, Profesor
role: STUDY_CHAIR
affiliation: CHU de Montpellier
name: Georges MOURAD, Profesor
role: STUDY_CHAIR
References: