- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01292525
Protocol Calcineurin Inhibitor (CNI) Weaning
22. mars 2016 oppdatert av: Nantes University Hospital
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
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®).
Studieoversikt
Status
Avsluttet
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
16
Fase
- Fase 3
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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-
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Nantes, Frankrike, 44093
- Nantes university hospital
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 80 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Aktiv komparator: 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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Eksperimentell: 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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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Renal function
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Renal function
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studiestol: Emmanuel MORELON, Profesor, CHU de Lyon
- Hovedetterforsker: Magali GIRAL, Profesor, CHU de Nantes
- Studiestol: Jean-Paul SOULILLOU, Profesor, CHU de Nantes
- Studiestol: Christophe LEGENDRE, Profesor, Hôpital Necker - AP-HP
- Studiestol: Georges MOURAD, Profesor, CHU de Montpellier
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. mai 2011
Primær fullføring (Faktiske)
1. mai 2015
Studiet fullført (Faktiske)
1. mai 2015
Datoer for studieregistrering
Først innsendt
8. februar 2011
Først innsendt som oppfylte QC-kriteriene
8. februar 2011
Først lagt ut (Anslag)
9. februar 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
23. mars 2016
Siste oppdatering sendt inn som oppfylte QC-kriteriene
22. mars 2016
Sist bekreftet
1. mai 2015
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 09/7-D
- 2010-019574-33 (EudraCT-nummer)
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