Steroid Withdrawal in Pediatric Kidney Transplant Recipients
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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.
Visão geral do estudo
Status
Condições
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Alabama
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Birmingham, Alabama, Estados Unidos, 35233
- University of Alabama
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California
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San Diego, California, Estados Unidos, 92103
- UCSD Medical Center
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- Denver Children's Hospital
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Florida
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Jacksonville, Florida, Estados Unidos, 32209
- University of Florida Health Science Center
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Emory Children's Center
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Louisiana
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New Orleans, Louisiana, Estados Unidos, 70112
- Tulane University Medical Center
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Maryland
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Baltimore, Maryland, Estados Unidos, 21201
- University of Maryland Medical Center
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Children's Hospital of Boston
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New Mexico
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Albuquerque, New Mexico, Estados Unidos, 87131
- University of New Mexico Health Science Center
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New York
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Buffalo, New York, Estados Unidos, 14222
- The Children's Hospital of Buffalo
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Valhalla, New York, Estados Unidos, 10595
- Westchester Medical Center
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Ohio
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Cleveland, Ohio, Estados Unidos, 44106
- Rainbow Babies and Childrens Hospital
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Cleveland, Ohio, Estados Unidos, 44106
- University Hospitals of Cleveland
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Pennsylvania
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Hershey, Pennsylvania, Estados Unidos, 17033
- Penn State College of Medicine
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Tennessee
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Memphis, Tennessee, Estados Unidos, 38103
- LeBonheur Children's Medical Center
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Texas
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San Antonio, Texas, Estados Unidos, 78207
- Christopher Goldsbury Center
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Washington
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Seattle, Washington, Estados Unidos, 98105
- Children's Hospital and Regional Medical Center
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53705
- University of Wisconsin
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Distrito Federal
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Mexico City, Distrito Federal, México, 06720
- Hospital Infantil de Mexico
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: 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.
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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.
Outros nomes:
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).
Outros nomes:
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.
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.
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
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.
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).
Outros nomes:
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Comparador Ativo: 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.
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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.
Outros nomes:
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).
Outros nomes:
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.
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.
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
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.
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).
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
Prazo: At 6 months and 2.5 years post-transplant
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At 6 months and 2.5 years post-transplant
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Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
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Graft and patient survival
Prazo: Throughout study
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Throughout study
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Biopsy-proven acute rejection
Prazo: Throughout study
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Throughout study
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Renal function, measured by serum creatinine and the calculated creatinine clearances
Prazo: Throughout study
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Throughout study
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Hypertension
Prazo: Throughout study
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Throughout study
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Cushingoid features
Prazo: Throughout study
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Throughout study
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Systolic and diastolic blood pressure levels
Prazo: Throughout study
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Throughout study
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Fasting lipid profile
Prazo: Throughout study
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Throughout study
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Colaboradores e Investigadores
Publicações e links úteis
Publicações Gerais
- Magee JC. Steroids in pediatric kidney transplantation: a balancing act in progress. Am J Transplant. 2010 Jan;10(1):6-7. doi: 10.1111/j.1600-6143.2009.02923.x. Epub 2009 Dec 17. No abstract available.
- Li L, Chang A, Naesens M, Kambham N, Waskerwitz J, Martin J, Wong C, Alexander S, Grimm P, Concepcion W, Salvatierra O, Sarwal MM. Steroid-free immunosuppression since 1999: 129 pediatric renal transplants with sustained graft and patient benefits. Am J Transplant. 2009 Jun;9(6):1362-72. doi: 10.1111/j.1600-6143.2009.02640.x. Epub 2009 May 13.
- Benfield MR, Bartosh S, Ikle D, Warshaw B, Bridges N, Morrison Y, Harmon W. A randomized double-blind, placebo controlled trial of steroid withdrawal after pediatric renal transplantation. Am J Transplant. 2010 Jan;10(1):81-8. doi: 10.1111/j.1600-6143.2009.02767.x. Epub 2009 Jul 28.
- McDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P, Wyatt R, Arar M, Liereman D, Bridges N, Harmon W; CCTPT Study Group. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant. 2008 May;8(5):984-9. doi: 10.1111/j.1600-6143.2008.02167.x.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Doenças renais
- Doenças Urológicas
- Insuficiência renal
- Insuficiência Renal Crônica
- Insuficiência Renal Crônica
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Agentes Autônomos
- Agentes do Sistema Nervoso Periférico
- Inibidores Enzimáticos
- Antiinflamatórios
- Agentes Antirreumáticos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Antieméticos
- Agentes gastrointestinais
- Glicocorticóides
- Hormônios
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Agentes Antineoplásicos Hormonais
- Agentes Neuroprotetores
- Agentes de proteção
- Agentes dermatológicos
- Agentes antibacterianos
- Inibidores da enzima citocromo P-450
- Antibióticos, Antineoplásicos
- Antifúngicos
- Agentes Antiprotozoários
- Antiparasitários
- Antimaláricos
- Antagonistas do ácido fólico
- Inibidores de Calcineurina
- Agentes Antidiscinesia
- Agentes Anti-Infecciosos Urinários
- Agentes renais
- Inibidores do citocromo P-450 CYP2C8
- Metilprednisolona
- Prednisona
- Tacrolimo
- Sirolimo
- Basiliximabe
- Ciclosporina
- Ciclosporinas
- Trimetoprima
- Sulfametoxazol
- Combinação de Medicamentos Trimetoprima e Sulfametoxazol
Outros números de identificação do estudo
- DAIT SW01
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Dados/documentos do estudo
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Conjunto de dados de participantes individuais
Identificador de informação: SDY133Comentários informativos: ImmPort study identifier is SDY133
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Protocolo de estudo
Identificador de informação: SDY133Comentários informativos: ImmPort study identifier is SDY133
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Study summary, -design,-demographics, -files et al.
Identificador de informação: SDY133Comentários informativos: ImmPort study identifier is SDY133
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