TerminatedNCT01292525Updated Mar 23, 2016

Protocol Calcineurin Inhibitor (CNI) Weaning

A Phase 3 interventional study of Tacrolimus and Placebo in Function of Renal Transplant, sponsored by Nantes University Hospital. Terminated at 1 site in France. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2016-03-23.

Sponsored by Nantes University Hospital · Phase 3, Interventional, and Treatment

Why this study was terminated

Difficulties of recruitment

Phase: Phase 3
Study type: Interventional
Enrollment: 16
Allocation: Randomized
Ages: 18 Years to 80 Years
Sex: All

Study 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®).

Conditions studied

Function of Renal Transplant

Keywords

Withdrawal of Tacrolimus and renal graft
renal allograft
stable renal function

In context

Lead sponsor

Nantes University Hospital is the lead sponsor of 825 studies on the registry; 195 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 80 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

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

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 16 participants (actual)

Study arms

Active comparator
Tacrolimus
Drug: Tacrolimus
Experimental
Withdrawal of Tacrolimus
Drug: Placebo

Interventions

DrugTacrolimus
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®).
DrugPlacebo
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.

What researchers measure

Primary outcomes

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).
Time frame: one year after complete withdrawal of Tacrolimus

Secondary outcomes

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

Study locations

1 site

Nantes University Hospital
Nantes, 44093, France

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 23, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01292525
Lead sponsor: Nantes University Hospital
First posted: Feb 9, 2011
Start date: May 2011
Primary completion: May 2015
Completion: May 2015
Last update: Mar 23, 2016

Study contacts

Magali GIRAL, Profesor

principal investigator · Nantes University Hospital

Jean-Paul SOULILLOU, Profesor

study chair · Nantes University Hospital

Christophe LEGENDRE, Profesor

study chair · Hôpital Necker - AP-HP

Emmanuel MORELON, Profesor

study chair · CHU de Lyon

Georges MOURAD, Profesor

study chair · CHU de Montpellier

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in May 2015. You cannot join it, but the record below documents what was studied.

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