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Steroid Withdrawal in Pediatric Kidney Transplant Recipients

19 października 2016 zaktualizowane przez: National Institute of Allergy and Infectious Diseases (NIAID)

A Double-Blind Randomized Trial of Steroid Withdrawal in Sirolimus- and Cyclosporine-Treated Primary Transplant Recipients

The purpose of this study is to examine the effects of withdrawing steroids on graft rejection and kidney functions in kidney transplant recipients between the ages of 0 and 20 years (prior to their 21st birthday).

Graft survival has improved in recent years in children with kidney transplants. One bad side effect of steroid maintenance therapy has been growth retardation. Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies. If steroids are removed, children might catch up in their growth and also might have fewer side effects of other kinds. This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

Children receiving kidney (renal) transplantation face distressing issues in post-transplantation including but not limited to growth retardation directly attributable to corticosteroids (steroids). It is hypothesized that robust immunosuppression with sirolimus and calcineurin inhibitors (cyclosporine or tacrolimus) in conjunction with induction therapy should enable successful steroid withdrawal. A steroid-free environment could lessen side effects by enabling a child to achieve catch-up growth, reducing the need for anti-hypertensive therapy, and reducing the risk of cardiovascular disease. This trial tests the objective of providing a steroid-free state without incurring the risk of increased incidence of acute transplant rejections.

Patients are enrolled prior to kidney transplantation and receive standard evaluations. Patients receive induction therapy with basiliximab preoperatively and on Day 4 after surgery. Immunosuppressive therapy begins with sirolimus and either cyclosporine or tacrolimus on Day 1 following surgery, and with corticosteroids the day of surgery. Infection prophylaxis with Bactrim is begun on Day 1 after surgery and center-specific anti-cytomegalovirus (CMV) therapy is given for all recipients of a CMV positive kidney. At 6 months post-transplantation, all patients who have not had an episode of acute rejection undergo a renal graft biopsy. Patients who are confirmed to be free of subclinical rejection are randomized to either undergo complete steroid withdrawal or continue maintenance on daily steroids. Patients receive either steroids or placebo, while continuing other immunosuppressive medications. Patients are segregated into weight groups for steroid withdrawal that occurs over months 7 to 13. Any acute rejection event during withdrawal is confirmed by renal biopsy and managed with methylprednisolone treatment. Patients are followed for 3 years post-transplantation for analysis of growth rate, blood pressure, lipid profile and renal function as measured by serum creatinine and calculated creatinine clearances. Post-transplantation clinic visits are weekly for the first 2 months, every 2 weeks until 13 months, weekly during Month 13, every 2 weeks through Month 18, and monthly until the study ends.

Patients who exhibit evidence of acute or subclinical rejection do not continue the steroid withdrawal trial and care is managed by their pediatric renal transplant center physicians.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

274

Faza

  • Faza 2

Kontakty i lokalizacje

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

Lokalizacje studiów

  • Meksyk
    • Distrito Federal
      • Mexico City, Distrito Federal, Meksyk, 06720
        • Hospital Infantil de Mexico
  • Stany Zjednoczone
    • Alabama
      • Birmingham, Alabama, Stany Zjednoczone, 35233
        • University of Alabama
    • California
      • San Diego, California, Stany Zjednoczone, 92103
        • UCSD Medical Center
    • Colorado
      • Aurora, Colorado, Stany Zjednoczone, 80045
        • Denver Children's Hospital
    • Florida
      • Jacksonville, Florida, Stany Zjednoczone, 32209
        • University of Florida Health Science Center
    • Georgia
      • Atlanta, Georgia, Stany Zjednoczone, 30322
        • Emory Children's Center
    • Louisiana
      • New Orleans, Louisiana, Stany Zjednoczone, 70112
        • Tulane University Medical Center
    • Maryland
      • Baltimore, Maryland, Stany Zjednoczone, 21201
        • University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, Stany Zjednoczone, 02115
        • Children's Hospital of Boston
    • New Mexico
      • Albuquerque, New Mexico, Stany Zjednoczone, 87131
        • University of New Mexico Health Science Center
    • New York
      • Buffalo, New York, Stany Zjednoczone, 14222
        • The Children's Hospital of Buffalo
      • Valhalla, New York, Stany Zjednoczone, 10595
        • Westchester Medical Center
    • Ohio
      • Cleveland, Ohio, Stany Zjednoczone, 44106
        • Rainbow Babies and Childrens Hospital
      • Cleveland, Ohio, Stany Zjednoczone, 44106
        • University Hospitals of Cleveland
    • Pennsylvania
      • Hershey, Pennsylvania, Stany Zjednoczone, 17033
        • Penn State College of Medicine
    • Tennessee
      • Memphis, Tennessee, Stany Zjednoczone, 38103
        • LeBonheur Children's Medical Center
    • Texas
      • San Antonio, Texas, Stany Zjednoczone, 78207
        • Christopher Goldsbury Center
    • Washington
      • Seattle, Washington, Stany Zjednoczone, 98105
        • Children's Hospital and Regional Medical Center
    • Wisconsin
      • Madison, Wisconsin, Stany Zjednoczone, 53705
        • University of Wisconsin

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

1 dzień do 20 lat (Dziecko, Dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

Inclusion Criteria:

Patients may be eligible for this study if they:

  • Are between the ages of 0 and 20 years (prior to their 21st birthday)
  • Are receiving their first living related (e.g.,kidney from a relative or unrelated donor) or cadaver donor transplant
  • Are willing to practice an acceptable method of birth control during the study, if women able to have children

Exclusion Criteria:

Patients will not be eligible for this study if they:

  • Have received multiple organs
  • Have received 2 or more transplants
  • Have an active infection (including tuberculosis), or cancer
  • Have used an experimental agent within 4 weeks of transplantation

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: Podwójnie

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Corticosteroid (steroid) withdrawal
All enrolled subjects who have not experienced an episode of acute rejection or other event resulting in removal from the study in the first 6 months after transplantation will undergo a protocol-driven biopsy at 6 months. Subjects with no clinical or histologic evidence of rejection will be eligible to be randomized and treated in a double-blinded (e.g., masked-neither subject nor health care providers will know treatment being received) fashion while continuing other immunosuppressive medications. Subjects in this arm will undergo complete steroid withdrawal by the end of 12 months post-transplant.
Lek: Basiliximab
Administered as a bolus intravenous injection. The first dose is given pre-operatively, the second dose is given on post-transplant day four. Dosage is determined by individual weight.
Inne nazwy:
  • Symulekt
  • Anti-CD25 monoclonal antibody, chimeric
Lek: Cyclosporine
Participants receiving cyclosporine microemulsion formula (in lieu of tacrolimus) will have the dose adjusted to maintain a whole blood trough Abbott TDx assay monoclonal level of 175-400 ng/mL (or an equivalent high pressure liquid chromatography (HPLC) level) for the first 2 weeks after transplant. The dose will subsequently be tapered to maintain a trough level of 175-300 ng/mL from week 3 to month 3, and 50-250 ng/mL from month 3 through the end of the study at month 36 (year 3).
Inne nazwy:
  • CsA
Lek: Tacrolimus
Participants receiving tacrolimus (in lieu of Cyclosporine) will have the dose adjusted to maintain a whole blood trough level between 10 and 15 ng/mL for the first 4weeks after transplant. Trough levels will be maintained between 5 and 10 ng/mL thereafter throughout the duration of the study.
Lek: Sirolimus
Participants take daily (orally, either as tablets or as liquid) starting on postoperative day 1 at a dose of 6 mg/m2 and will be adjusted to maintain a trough level of 10-20 ng/mL throughout the study.
Lek: Methylprednisolone
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
Lek: Prednisone
Administered orally beginning on Post-Op Day 2 and maintained for all participants until day 180. Randomization will determine whether patients will maintain this treatment following day 180.
Lek: Bactrim
All subjects will receive TMP SMX (Bactrim), pneumocystis jiroveci (carinii) prophylaxis, beginning on postoperative day 1 and continuing for 6 months following transplant. Dosage: 10 mg/kg taken orally three times weekly (maximum dose 160 mg).
Inne nazwy:
  • trimetoprim/sulfametoksazol
  • TMP SMX
Aktywny komparator: Control Treatment
All enrolled subjects who have not experienced an episode of acute rejection or other event resulting in removal from the study in the first 6 months after transplantation will undergo a protocol-driven biopsy at 6 months. Subjects with no clinical or histologic evidence of rejection will be eligible to be randomized and treated in a double-blinded (e.g., masked-neither subject nor health care providers will know treatment being received) fashion while continuing other immunosuppressive medications. Subjects in this arm will be maintained on low-dose (0.15 mg/kg/day) daily steroids.
Lek: Basiliximab
Administered as a bolus intravenous injection. The first dose is given pre-operatively, the second dose is given on post-transplant day four. Dosage is determined by individual weight.
Inne nazwy:
  • Symulekt
  • Anti-CD25 monoclonal antibody, chimeric
Lek: Cyclosporine
Participants receiving cyclosporine microemulsion formula (in lieu of tacrolimus) will have the dose adjusted to maintain a whole blood trough Abbott TDx assay monoclonal level of 175-400 ng/mL (or an equivalent high pressure liquid chromatography (HPLC) level) for the first 2 weeks after transplant. The dose will subsequently be tapered to maintain a trough level of 175-300 ng/mL from week 3 to month 3, and 50-250 ng/mL from month 3 through the end of the study at month 36 (year 3).
Inne nazwy:
  • CsA
Lek: Tacrolimus
Participants receiving tacrolimus (in lieu of Cyclosporine) will have the dose adjusted to maintain a whole blood trough level between 10 and 15 ng/mL for the first 4weeks after transplant. Trough levels will be maintained between 5 and 10 ng/mL thereafter throughout the duration of the study.
Lek: Sirolimus
Participants take daily (orally, either as tablets or as liquid) starting on postoperative day 1 at a dose of 6 mg/m2 and will be adjusted to maintain a trough level of 10-20 ng/mL throughout the study.
Lek: Methylprednisolone
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
Lek: Prednisone
Administered orally beginning on Post-Op Day 2 and maintained for all participants until day 180. Randomization will determine whether patients will maintain this treatment following day 180.
Lek: Bactrim
All subjects will receive TMP SMX (Bactrim), pneumocystis jiroveci (carinii) prophylaxis, beginning on postoperative day 1 and continuing for 6 months following transplant. Dosage: 10 mg/kg taken orally three times weekly (maximum dose 160 mg).
Inne nazwy:
  • trimetoprim/sulfametoksazol
  • TMP SMX

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Ramy czasowe
Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
Ramy czasowe: At 6 months and 2.5 years post-transplant
At 6 months and 2.5 years post-transplant

Miary wyników drugorzędnych

Miara wyniku
Ramy czasowe
Graft and patient survival
Ramy czasowe: Throughout study
Throughout study
Biopsy-proven acute rejection
Ramy czasowe: Throughout study
Throughout study
Renal function, measured by serum creatinine and the calculated creatinine clearances
Ramy czasowe: Throughout study
Throughout study
Hypertension
Ramy czasowe: Throughout study
Throughout study
Cushingoid features
Ramy czasowe: Throughout study
Throughout study
Systolic and diastolic blood pressure levels
Ramy czasowe: Throughout study
Throughout study
Fasting lipid profile
Ramy czasowe: Throughout study
Throughout study

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Współpracownicy

Cooperative Clinical Trials in Pediatric Transplantation

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

Przydatne linki

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 stycznia 2001

Zakończenie podstawowe (Rzeczywisty)

1 czerwca 2005

Ukończenie studiów (Rzeczywisty)

1 czerwca 2005

Daty rejestracji na studia

Pierwszy przesłany

29 sierpnia 2001

Pierwszy przesłany, który spełnia kryteria kontroli jakości

30 sierpnia 2001

Pierwszy wysłany (Oszacować)

31 sierpnia 2001

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

21 października 2016

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

19 października 2016

Ostatnia weryfikacja

1 października 2016

Więcej informacji

Terminy związane z tym badaniem

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • DAIT SW01

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Badanie danych/dokumentów

  1. Indywidualny zestaw danych uczestnika
    Identyfikator informacji: SDY133
    Komentarze do informacji: ImmPort study identifier is SDY133
  2. Protokół badania
    Identyfikator informacji: SDY133
    Komentarze do informacji: ImmPort study identifier is SDY133
  3. Study summary, -design,-demographics, -files et al.
    Identyfikator informacji: SDY133
    Komentarze do informacji: ImmPort study identifier is SDY133

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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