Protocol Calcineurin Inhibitor (CNI) Weaning

Phase 3

Terminated

• Conditions: Function of Renal Transplant
• Interventions: Drug: Placebo; Drug: Tacrolimus

• Registration Number: NCT01292525
• Lead Sponsor: Nantes University Hospital

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®).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-02-08
• Study First Submitted QC: 2011-02-08
• Study First Posted: 2011-02-09
• Study Start: 2011-05
• Status Verified: 2015-05
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Last Update Submitted: 2016-03-22
• Last Update Posted: 2016-03-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 16

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Withdrawal of Tacrolimus	Placebo	-
Tacrolimus	Tacrolimus	-

Primary Outcome Measures

Name	Time	Method
Renal function	one year after complete withdrawal of Tacrolimus	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

Name	Time	Method
Chronic rejection	One year after complete withdrawal	Rate of chronic rejection histologically proven by biopsy according to Banff classification 2009,
Steroid-resistant rejection	One year after complete withdrawal	Rates of steroid-resistant rejection
Graft survival	One year after complete withdrawal	Rate of return to dialysis (graft survival)
Renal function	one year after complete withdrawal	Improvement of renal function by measuring serum creatinine, using the original MDRD equation,
Anti-HLA antibodies	One year after complete withdrawal	Appearance of anti-HLA donor specific and non-donor specific antibodies measured by the technique Luminex
Histological lesions of rejection	One year after complete withdrawal	The appearance of histological lesions of cellular or humoral acute or chronic or subclinical rejection on the biopsy protocol
Acute rejection	one year after complete withdrawal	Rate of histologically proven acute rejection by biopsy according to Banff classification 2009,
Cancer and infections	one year after complete withdrawal	Incidence of cancer and infections
Patients survival	One year after complete withdrawal	Survival rate of patients
Histological lesions of fibrosis	One year after complete withdrawal	Onset or worsening of histological lesions of interstitial fibrosis and tubular atrophy on biopsy inflammatory
Hypertension, hyperglycemia and hyperlipidemia	One year after complete withdrawal	Incidence of hypertension, hyperglycemia and hyperlipidemia
Quality of life	One year after complete withdrawal	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)

Trial Locations

Locations (1)

Nantes University Hospital; 🇫🇷 Nantes, France