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Steroid Withdrawal in Pediatric Kidney Transplant Recipients

19. října 2016 aktualizováno: 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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.

Přehled studie

Postavení

Ukončeno

Podmínky

Intervence / Léčba

Detailní popis

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 studie

Intervenční

Zápis (Aktuální)

274

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

1 den až 20 let (Dítě, Dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Dvojnásobek

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Lék: 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.
Ostatní jména:
  • Simulekt
  • Anti-CD25 monoclonal antibody, chimeric
Lék: 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).
Ostatní jména:
  • ČsA
Lék: 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.
Lék: 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.
Lék: Methylprednisolone
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
Lék: 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.
Lék: 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).
Ostatní jména:
  • trimethoprim/sulfamethoxazol
  • TMP SMX
Aktivní komparátor: 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.
Lék: 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.
Ostatní jména:
  • Simulekt
  • Anti-CD25 monoclonal antibody, chimeric
Lék: 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).
Ostatní jména:
  • ČsA
Lék: 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.
Lék: 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.
Lék: Methylprednisolone
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
Lék: 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.
Lék: 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).
Ostatní jména:
  • trimethoprim/sulfamethoxazol
  • TMP SMX

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Časové okno
Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
Časové okno: At 6 months and 2.5 years post-transplant
At 6 months and 2.5 years post-transplant

Sekundární výstupní opatření

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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

National Institute of Allergy and Infectious Diseases (NIAID)

Spolupracovníci

Cooperative Clinical Trials in Pediatric Transplantation

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. ledna 2001

Primární dokončení (Aktuální)

1. června 2005

Dokončení studie (Aktuální)

1. června 2005

Termíny zápisu do studia

První předloženo

29. srpna 2001

První předloženo, které splnilo kritéria kontroly kvality

30. srpna 2001

První zveřejněno (Odhad)

31. srpna 2001

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

21. října 2016

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

19. října 2016

Naposledy ověřeno

1. října 2016

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • DAIT SW01

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu 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.

Studijní data/dokumenty

  1. Soubor dat jednotlivých účastníků
    Identifikátor informace: SDY133
    Komentáře k informacím: ImmPort study identifier is SDY133
  2. Protokol studie
    Identifikátor informace: SDY133
    Komentáře k informacím: ImmPort study identifier is SDY133
  3. Study summary, -design,-demographics, -files et al.
    Identifikátor informace: SDY133
    Komentáře k informacím: ImmPort study identifier is SDY133

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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