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

12 listopada 2013 zaktualizowane przez: 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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

668

Faza

  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

12 lat i starsze (Dziecko, Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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.
Lek: 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.
Inne nazwy:
  • Prograf, FK506
Lek: mycophenolate mofetil
Oral
Inne nazwy:
  • CellCept, MMF
Aktywny komparator: 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.
Lek: mycophenolate mofetil
Oral
Inne nazwy:
  • CellCept, MMF
Lek: 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.
Inne nazwy:
  • Advagraf, FK506, FKMR, MR4, Astagraf XL
Aktywny komparator: 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.
Lek: mycophenolate mofetil
Oral
Inne nazwy:
  • CellCept, MMF
Lek: 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.
Inne nazwy:
  • Neoral, CsA

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Percentage of Participants With Efficacy Failure
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Patient Survival at One Year
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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).

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Astellas Pharma Inc

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 czerwca 2003

Zakończenie podstawowe (Rzeczywisty)

1 marca 2005

Ukończenie studiów (Rzeczywisty)

1 marca 2009

Daty rejestracji na studia

Pierwszy przesłany

10 lipca 2003

Pierwszy przesłany, który spełnia kryteria kontroli jakości

11 lipca 2003

Pierwszy wysłany (Oszacować)

14 lipca 2003

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

5 grudnia 2013

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

12 listopada 2013

Ostatnia weryfikacja

1 listopada 2013

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • 02-0-158

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