A Double-Blind Randomized Trial of Steroid Withdrawal in Sirolimus- and Cyclosporine-Treated Primary Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 274
- 试验地点
- 19
- 主要终点
- Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
研究概览
简要总结
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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 1 Day 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Basiliximab (Drug)
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.
干预措施: Cyclosporine (Drug)
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.
干预措施: Tacrolimus (Drug)
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.
干预措施: Sirolimus (Drug)
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.
干预措施: Methylprednisolone (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Bactrim (Drug)
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.
干预措施: Basiliximab (Drug)
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.
干预措施: Cyclosporine (Drug)
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.
干预措施: Tacrolimus (Drug)
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.
干预措施: Sirolimus (Drug)
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.
干预措施: Methylprednisolone (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Bactrim (Drug)
结局指标
主要结局
Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
时间窗: At 6 months and 2.5 years post-transplant
次要结局
- Graft and patient survival(Throughout study)
- Hypertension(Throughout study)
- Cushingoid features(Throughout study)
- Fasting lipid profile(Throughout study)
- Renal function, measured by serum creatinine and the calculated creatinine clearances(Throughout study)
- Systolic and diastolic blood pressure levels(Throughout study)
- Biopsy-proven acute rejection(Throughout study)