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
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Tipo di studio
Tipo di studio
Iscrizione (Effettivo)
Iscrizione
Fase
Fase
- Fase 3
Contatti e Sedi
Luoghi di studio
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Nantes, Francia, 44093
- Nantes university hospital
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Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
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Comparatore attivo: 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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Sperimentale: 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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Renal function
Lasso di tempo: 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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Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Renal function
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Collaboratori e investigatori
Sponsor
Sponsor
Investigatori
Investigatori
- Cattedra di studio: Emmanuel MORELON, Profesor, CHU de Lyon
- Investigatore principale: Magali GIRAL, Profesor, CHU de Nantes
- Cattedra di studio: Jean-Paul SOULILLOU, Profesor, CHU de Nantes
- Cattedra di studio: Christophe LEGENDRE, Profesor, Hôpital Necker - AP-HP
- Cattedra di studio: Georges MOURAD, Profesor, CHU de Montpellier
Studiare le date dei record
Studia le date principali
Inizio studio
Inizio studio
Completamento primario (Effettivo)
Completamento primario
Completamento dello studio (Effettivo)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- 09/7-D
- 2010-019574-33 (Numero EudraCT)
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