Protocol Calcineurin Inhibitor (CNI) Weaning
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
Visão geral do estudo
Status
Status
Condições
Condições
Intervenção / Tratamento
Intervenção / Tratamento
Tipo de estudo
Tipo de estudo
Inscrição (Real)
Inscrição
Estágio
Estágio
- Fase 3
Contactos e Locais
Locais de estudo
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Nantes, França, 44093
- Nantes university hospital
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Critérios de participação
Critérios de elegibilidade
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Número de braços
Armas e Intervenções
Grupo de Participantes / BraçoGrupo de Participantes / Braço |
Intervenção / TratamentoIntervenção / Tratamento |
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Comparador Ativo: Tacrolimus
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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®).
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Experimental: Withdrawal of Tacrolimus
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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.
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O que o estudo está medindo?
Medidas de resultados primários
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Renal function
Prazo: one year after complete withdrawal of Tacrolimus
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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).
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one year after complete withdrawal of Tacrolimus
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Medidas de resultados secundários
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Renal function
Prazo: one year after complete withdrawal
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Improvement of renal function by measuring serum creatinine, using the original MDRD equation,
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one year after complete withdrawal
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Acute rejection
Prazo: one year after complete withdrawal
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Rate of histologically proven acute rejection by biopsy according to Banff classification 2009,
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one year after complete withdrawal
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Chronic rejection
Prazo: One year after complete withdrawal
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Rate of chronic rejection histologically proven by biopsy according to Banff classification 2009,
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One year after complete withdrawal
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Steroid-resistant rejection
Prazo: One year after complete withdrawal
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Rates of steroid-resistant rejection
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One year after complete withdrawal
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Graft survival
Prazo: One year after complete withdrawal
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Rate of return to dialysis (graft survival)
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One year after complete withdrawal
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Cancer and infections
Prazo: one year after complete withdrawal
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Incidence of cancer and infections
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one year after complete withdrawal
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Patients survival
Prazo: One year after complete withdrawal
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Survival rate of patients
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One year after complete withdrawal
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Anti-HLA antibodies
Prazo: One year after complete withdrawal
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Appearance of anti-HLA donor specific and non-donor specific antibodies measured by the technique Luminex
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One year after complete withdrawal
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Histological lesions of rejection
Prazo: One year after complete withdrawal
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The appearance of histological lesions of cellular or humoral acute or chronic or subclinical rejection on the biopsy protocol
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One year after complete withdrawal
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Histological lesions of fibrosis
Prazo: One year after complete withdrawal
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Onset or worsening of histological lesions of interstitial fibrosis and tubular atrophy on biopsy inflammatory
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One year after complete withdrawal
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Hypertension, hyperglycemia and hyperlipidemia
Prazo: One year after complete withdrawal
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Incidence of hypertension, hyperglycemia and hyperlipidemia
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One year after complete withdrawal
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Quality of life
Prazo: One year after complete withdrawal
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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)
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One year after complete withdrawal
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Cadeira de estudo: Emmanuel MORELON, Profesor, CHU de Lyon
- Investigador principal: Magali GIRAL, Profesor, CHU de Nantes
- Cadeira de estudo: Jean-Paul SOULILLOU, Profesor, CHU de Nantes
- Cadeira de estudo: Christophe LEGENDRE, Profesor, Hôpital Necker - AP-HP
- Cadeira de estudo: Georges MOURAD, Profesor, CHU de Montpellier
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Início do estudo
Conclusão Primária (Real)
Conclusão Primária
Conclusão do estudo (Real)
Conclusão do estudo
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Primeira postagem
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última Atualização Postada
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
Outros números de identificação do estudo
- 09/7-D
- 2010-019574-33 (Número EudraCT)
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