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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

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

      • Nantes, Frankrike, 44093
        • Nantes university hospital

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
Aktiv komparator: Tacrolimus
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®).
Eksperimentell: Withdrawal of Tacrolimus
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.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Renal function
Tidsramme: one year after complete withdrawal of Tacrolimus
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

Sekundære resultatmål

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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

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

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