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Comparative Study of Modified Release (MR) Tacrolimus/Mycophenolate Mofetil (MMF) in de Novo Kidney Transplant Recipients

12 novembre 2013 aggiornato da: Astellas Pharma Inc

A Phase III, Randomized, Open-Label, Comparative, Multi-Center Study to Assess the Safety and Efficacy of Prograf (Tacrolimus)/MMF, Modified Release (MR) Tacrolimus/MMF and Neoral (Cyclosporine)/MMF in de Novo Kidney Transplant Recipients

The purpose of this study is to compare the safety and efficacy of tacrolimus/mycophenolate mofetil (MMF), cyclosporine/MMF and tacrolimus modified release/MMF in de novo kidney transplant recipients.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

This was a 3 arm randomized, open-label, comparative, multi-center study in de novo kidney transplant recipients at 60 centers in the U.S., Canada and Brazil.

The study consisted of a 1-year post-transplant efficacy and safety study with a clinical continuation phase of a minimum of 2 years or until commercial availability of tacrolimus modified release, unless the Data Safety Monitoring Board or sponsor specified otherwise.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

668

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Brasile
      • Porto Alegre, Brasile, 90240-520
      • Rio de Janeiro, Brasile, 21041-003
      • Sao Paulo, Brasile, 04038-002
      • Sao Paulo, Brasile, 04013-043
      • Sao Paulo, Brasile, 05465-040
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Ontario
      • Toronto, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Stati Uniti
    • Alabama
      • Birmingham, Alabama, Stati Uniti, 35294
      • Mobile, Alabama, Stati Uniti, 36617
    • California
      • Loma Linda, California, Stati Uniti, 92354
      • Los Angeles, California, Stati Uniti, 90033
      • Los Angeles, California, Stati Uniti, 90057
      • Los Angeles, California, Stati Uniti, 90058
      • Los Angeles, California, Stati Uniti, 90095-7306
      • Palo Alto, California, Stati Uniti, 94304
      • San Diego, California, Stati Uniti, 92103
      • San Diego, California, Stati Uniti, 92123
      • San Francisco, California, Stati Uniti, 94115
    • Colorado
      • Denver, Colorado, Stati Uniti, 80262
    • District of Columbia
      • Washington, District of Columbia, Stati Uniti, 20010
    • Florida
      • Gainesville, Florida, Stati Uniti, 32610-0224
      • Jacksonville, Florida, Stati Uniti, 32216
    • Georgia
      • Augusta, Georgia, Stati Uniti, 30912
    • Illinois
      • Chicago, Illinois, Stati Uniti, 60637
      • Chicago, Illinois, Stati Uniti, 60612
    • Indiana
      • Indianapolis, Indiana, Stati Uniti, 46202
    • Kentucky
      • Lexington, Kentucky, Stati Uniti, 40536
    • Louisiana
      • New Orleans, Louisiana, Stati Uniti, 70112
      • New Orleans, Louisiana, Stati Uniti, 70121
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti, 02214
    • Michigan
      • Ann Arbor, Michigan, Stati Uniti, 48109-0364
      • Detroit, Michigan, Stati Uniti, 48202
    • New Jersey
      • Livingston, New Jersey, Stati Uniti, 07039
      • New Brunswick, New Jersey, Stati Uniti, 08901
    • New York
      • Albany, New York, Stati Uniti, 12208
      • Buffalo, New York, Stati Uniti, 14203
      • New York, New York, Stati Uniti, 10029
      • Valhalla, New York, Stati Uniti, 10595
    • North Carolina
      • Chapel Hill, North Carolina, Stati Uniti, 27599-7211
      • Durham, North Carolina, Stati Uniti, 27710
    • Ohio
      • Cincinnati, Ohio, Stati Uniti, 45267
    • Oregon
      • Portland, Oregon, Stati Uniti, 97210
      • Portland, Oregon, Stati Uniti, 97239-2940
    • Pennsylvania
      • Harrisburg, Pennsylvania, Stati Uniti, 17104
      • Philadelphia, Pennsylvania, Stati Uniti, 19104
      • Philadelphia, Pennsylvania, Stati Uniti, 19107
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37212-4750
    • Texas
      • Dallas, Texas, Stati Uniti, 75246
      • Dallas, Texas, Stati Uniti, 75235
      • Houston, Texas, Stati Uniti, 77030
      • San Antonio, Texas, Stati Uniti, 78229-3900
    • Utah
      • Salt Lake City, Utah, Stati Uniti, 84132
    • Virginia
      • Fairfax, Virginia, Stati Uniti, 22031
    • Wisconsin
      • Madison, Wisconsin, Stati Uniti, 53792-7375
      • Milwaukee, Wisconsin, Stati Uniti, 53226

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

12 anni e precedenti (Bambino, Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Recipient of a primary or retransplanted non-human leukocyte antigen (HLA)-identical living or non-HLA-identical cadaveric kidney transplant
  • Age greater or equal to 12 years

Exclusion Criteria:

  • Recipient or donor is known seropositive for human immunodeficiency virus (HIV)
  • Has current malignancy or history of malignancy
  • Has significant liver disease
  • Has uncontrolled concomitant infection or any other unstable medical condition
  • Is receiving everolimus or enteric coated mycophenolic acid at any time during the study
  • Received kidney with a cold ischemia time of equal or more than 36 hours
  • Received kidney transplant from a cadaveric donor equal or more than 60 years of age
  • Received intravenous immunoglobulin (IVIG) therapy prior to randomization

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Tacrolimus
Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
Droga: Tacrolimus
The target range for whole blood tacrolimus trough concentrations was the recommended trough concentration range for Prograf: 7 to 16 ng/mL for days 0 through 90 and 5 to 15 ng/mL thereafter.
Altri nomi:
  • Prograf, FK506
Droga: mycophenolate mofetil
Oral
Altri nomi:
  • CellCept, MMF
Comparatore attivo: Tacrolimus Modified Release
Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
Droga: mycophenolate mofetil
Oral
Altri nomi:
  • CellCept, MMF
Droga: Tacrolimus Modified Release (MR)
The target range for whole blood tacrolimus trough concentrations was 7 to 16 ng/mL for days 0 through 90, and 5 to 15 ng/mL thereafter.
Altri nomi:
  • Advagraf, FK506, FKMR, MR4, Astagraf XL
Comparatore attivo: Cyclosporine
Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
Droga: mycophenolate mofetil
Oral
Altri nomi:
  • CellCept, MMF
Droga: cyclosporine microemulsion
The target range for whole blood cyclosporine trough concentrations was 125 to 400 ng/mL for days 0 through 90, and 100 to 300 ng/mL thereafter.
Altri nomi:
  • Neoral, CsA

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage of Participants With Efficacy Failure
Lasso di tempo: one year

Efficacy failure is defined as any participant who died, experienced a graft failure (permanent return to dialysis [> 30 days] or retransplant), had a biopsy-confirmed (Banff Grade ≥ I) acute rejection (BCAR), or was lost to follow-up.

Biopsies were graded according to the 1997 Banff criteria:

Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
one year

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Patient Survival at One Year
Lasso di tempo: One year
Patient survival is defined as any participant who is known to be alive one year after the skin closure date. Participants who died or whose outcome was unknown at one year were considered to be non-survivors.
One year
Graft Survival at One Year
Lasso di tempo: One year

Graft survival defined as any participant who did not meet the criteria for graft loss, where graft loss is defined as any re-transplant, permanent return to dialysis (> 30 days), patient death, or participant whose outcome at one year was unknown.

Participants were only counted once regardless of how many criteria were met.
One year
Percentage of Participants With Biopsy Confirmed Acute Rejection at 6 and 12 Months
Lasso di tempo: Six months and 12 months

Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 1997 Banff criteria:

Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.

Acute rejection is defined as a grade ≥ I.
Six months and 12 months
Time to First Biopsy-confirmed Acute Rejection Episode
Lasso di tempo: one year

Time to first biopsy-confirmed acute rejection episode defined as the number of days from skin closure (Day 0) to the date of biopsy. Rejection episodes were confirmed by biopsy by the clinical site pathologist and graded according to the 1997 Banff criteria:

Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.

Acute rejection is defined as a grade ≥ I.
one year
Number of Participants Requiring Anti-lymphocyte Antibody Therapy for Treatment of Rejection
Lasso di tempo: one year

Rejection episodes were confirmed by biopsy by the clinical site pathologist. Participants with histologically-proven Banff Grade II or III rejection or participants with steroid-resistant rejection were treated with anti-lymphocyte antibody treatment according to institutional practice.

Biopsies were graded according to the 1997 Banff criteria:

Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
one year
Severity of Acute Rejection
Lasso di tempo: one year

Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 1997 Banff criteria:

Borderline: No intimal arteritis present but foci of mild tubulitis; Grade IA: Significant interstitial infiltration and foci of moderate tubulitis; Grade IB: Significant interstitial infiltration and foci of severe tubulitis; Grade IIA: Mild to moderate intimal arteritis in at least 1 arterial cross section Grade IIB: Severe intimal arteritis comprising >25% of the luminal area lost in at least 1 arterial cross section; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
one year
Number of Participants Experiencing Multiple Rejection Episodes
Lasso di tempo: one year
This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated.
one year
Number of Participants With Clinically Treated Acute Rejection Episodes
Lasso di tempo: one year
A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy.
one year
Number of Participants With Treatment Failure
Lasso di tempo: one year
Treatment failure was defined as the discontinuation of randomized study drug for any reason. Participants who met the definition of treatment failure were to be followed throughout the 12-month treatment period.
one year
Number of Participants Who Crossed Over Due to Treatment Failure
Lasso di tempo: one year
Participants were allowed to cross over to an alternative primary immunosuppressive regimen (either to the tacrolimus or cyclosporine treatment arms) to address an adverse event which led to randomized study drug discontinuation or in the case of severe or refractory rejection. Crossover to the modified release tacrolimus treatment arm was not permitted.
one year
Change From Month 1 in Serum Creatinine at Month 6 and Month 12
Lasso di tempo: Month 1, Month 6, and Month 12
Renal function was assessed by the change from Month 1 in serum creatinine six months and 12 months after transplant.
Month 1, Month 6, and Month 12
Change From Month 1 in Creatinine Clearance at Month 6 and Month 12
Lasso di tempo: Month 1, Month 6, and Month 12
Renal function was assessed by creatinine clearance, calculated using the Cockcroft-Gault formula.
Month 1, Month 6, and Month 12
Kaplan-Meier Estimate of Patient Survival at the End of the Study
Lasso di tempo: End of study (maximum time on study was 1,941 days).
Patient survival was defined as any participant who was alive at the end of the study. Patient survival was censored at the time of last follow-up contact.
End of study (maximum time on study was 1,941 days).
Kaplan-Meier Estimate of Graft Survival at the End of the Study
Lasso di tempo: End of study (maximum time on study was 1,941 days).

Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was any retransplant or the permanent return to dialysis (more than 30 days) or patient death.

Graft survival was censored at the time of last follow-up contact.
End of study (maximum time on study was 1,941 days).

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Astellas Pharma Inc

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 giugno 2003

Completamento primario (Effettivo)

1 marzo 2005

Completamento dello studio (Effettivo)

1 marzo 2009

Date di iscrizione allo studio

Primo inviato

10 luglio 2003

Primo inviato che soddisfa i criteri di controllo qualità

11 luglio 2003

Primo Inserito (Stima)

14 luglio 2003

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

5 dicembre 2013

Ultimo aggiornamento inviato che soddisfa i criteri QC

12 novembre 2013

Ultimo verificato

1 novembre 2013

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 02-0-158

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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