Protocol Calcineurin Inhibitor (CNI) Weaning

NCT01292525 | Terminated Phase 3 DMC

• 2 other identifiers: 09/7-D2010-019574-33
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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®).

Conditions

Function of Renal Transplant

Keywords

Withdrawal of Tacrolimus and renal graft; renal allograft; stable renal function

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• Renal function

  one year after complete withdrawal

• Acute rejection

  one year after complete withdrawal

• Chronic rejection

  One year after complete withdrawal

• Steroid-resistant rejection

  One year after complete withdrawal

• Graft survival

  One year after complete withdrawal

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

Drug: Tacrolimus

Withdrawal of Tacrolimus

EXPERIMENTAL

Drug: Placebo

Interventions

Tacrolimus DRUG

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®).

Tacrolimus

Placebo DRUG

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.

Withdrawal of Tacrolimus

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• 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.
• 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,
• 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.

You may not qualify if:

• 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 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,

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

Nantes University Hospital

Nantes, 44093, France

Location

Related Publications (1)

• Masset C, Dantal J, Soulillou JP, Walencik A, Delbos F, Brouard S, Giral M; Nantes DIVAT Consortium. Case Report: Long-term observations from the tacrolimus weaning randomized clinical trial depicts the challenging aspects for determination of low-immunological risk patients. Front Immunol. 2022 Nov 28;13:1021481. doi: 10.3389/fimmu.2022.1021481. eCollection 2022.

  PMID: 36518770 DERIVED

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Magali GIRAL, Profesor

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

• Jean-Paul SOULILLOU, Profesor

  Nantes University Hospital

  STUDY CHAIR

• Christophe LEGENDRE, Profesor

  Hôpital Necker - AP-HP

  STUDY CHAIR

• Emmanuel MORELON, Profesor

  Hospices Civils de Lyon

  STUDY CHAIR

• Georges MOURAD, Profesor

  CHU de Montpellier

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 8, 2011
• First Posted: February 9, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: March 23, 2016

Record last verified: 2015-05

Locations

FR (1)