Protocol Calcineurin Inhibitor (CNI) Weaning

Function of Renal Transplant Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01292525
• Other study ID #: 09/7-D
• Secondary ID: 2010-019574-33
• Status: Terminated
• Phase: Phase 3
• First received: February 8, 2011
• Last updated: March 22, 2016
• Start date: May 2011
• Est. completion date: May 2015

Study information

• Verified date: May 2015
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France : AFSSAPS
• Study type: Interventional

Clinical Trial 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®).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Function of Renal Transplant

Intervention

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®).
• 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.

Locations

Country	Name	City	State
France	Nantes University Hospital	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal function	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).	one year after complete withdrawal of Tacrolimus	Yes
Secondary	Renal function	Improvement of renal function by measuring serum creatinine, using the original MDRD equation,	one year after complete withdrawal	Yes
Secondary	Acute rejection	Rate of histologically proven acute rejection by biopsy according to Banff classification 2009,	one year after complete withdrawal	No
Secondary	Chronic rejection	Rate of chronic rejection histologically proven by biopsy according to Banff classification 2009,	One year after complete withdrawal	No
Secondary	Steroid-resistant rejection	Rates of steroid-resistant rejection	One year after complete withdrawal	No
Secondary	Graft survival	Rate of return to dialysis (graft survival)	One year after complete withdrawal	No
Secondary	Cancer and infections	Incidence of cancer and infections	one year after complete withdrawal	No
Secondary	Patients survival	Survival rate of patients	One year after complete withdrawal	No
Secondary	Anti-HLA antibodies	Appearance of anti-HLA donor specific and non-donor specific antibodies measured by the technique Luminex	One year after complete withdrawal	No
Secondary	Histological lesions of rejection	The appearance of histological lesions of cellular or humoral acute or chronic or subclinical rejection on the biopsy protocol	One year after complete withdrawal	No
Secondary	Histological lesions of fibrosis	Onset or worsening of histological lesions of interstitial fibrosis and tubular atrophy on biopsy inflammatory	One year after complete withdrawal	No
Secondary	Hypertension, hyperglycemia and hyperlipidemia	Incidence of hypertension, hyperglycemia and hyperlipidemia	One year after complete withdrawal	No
Secondary	Quality of life	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)	One year after complete withdrawal	No