A 24-month, Multi-center, Single Arm, Prospective Study to Evaluate Renal Function, Efficacy, Safety and Tolerability of Everolimus in Combination With Reduced Exposure Cyclosporine or Tacrolimus in Paediatric Liver Transplant Recipients.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Change From Baseline in Estimated Glomerular Filtration Rate - Month 12
研究概览
简要总结
This study was designed to assess the evolution of renal function and to collect efficacy, safety, and tolerability data of everolimus in co-exposure with reduced CNI in paediatric liver transplant recipients.
详细描述
Study is completed (was active and ongoing but no longer recruiting since December 2014). The study Data Monitoring Committee meeting communicated to Novartis the following safety findings in the study population: high rate of premature discontinuation of study medication, high rate of post-transplant lymphoproliferative disease and high rate of related serious infections leading to hospitalization. In light of the safety findings, Novartis followed the DMC recommendation to discontinue the study medication in this age group and to stop enrolling new patients in this study (regardless of age).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent from both parents or legal guardian(s) prior to patient participation in the study.
- •Paediatric liver transplant recipients aged greater than or equal to 1 month and younger than 18 years of age.
- •Paediatric recipients at the earliest 1 month and latest 6 month after liver transplantation.
排除标准
- •Patients with hepato-biliary malignancies and/or patients transplanted due to fulminant hepatitis /acute liver failure.
- •Presence of thrombosis of any major hepatic arteries, major/reconstructed hepatic veins, portal vein or inferior vena cava at any time prior to the start of study drug.
- •Patients with serum creatinine value >2 times age-related ULN at Baseline or who received renal replacement therapy within one week prior to the start of study drug and patients with a confirmed spot urine protein/creatinine ratio indicating a urinary protein excretion >500 mg/m2/24 hrs, at Baseline.
- •Patients with clinically significant systemic infection and/or in a critical care setting requiring life support measures such as mechanical ventilation, dialysis, or vasopressor agents.
- •Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
- •Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive βHCG laboratory test (>9 mIU/mL) at Baseline.
- •Female patients of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they agree for abstinence from sexual activity.
研究组 & 干预措施
Everolimus based regimen
Conversion at Baseline from an immunosuppressive regimen which contains either cyclosporine (CsA) or tacrolimus (TAC) with or without mycophenolic acid (MPA), with or without corticosteroids in a regimen which contains everolimus combined reduced dose of either cyclosporine (CsA) or tacrolimus (TAC).
The dosing schedule was twice daily, 12 hours apart.
干预措施: Introduction of everolimus with reduced cyclosporine or tacrolimus dose, the earliest 1 month and the latest 6 months after liver transplantation. (Drug)
结局指标
主要结局
Change From Baseline in Estimated Glomerular Filtration Rate - Month 12
时间窗: Baseline, Month 12
Evolution of renal function assessed by estimated Glomerular Filtration Rate (eGFR) calculated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula (Schwartz 2009), expressed in mean change in eGFR of CKiD between start of study (baseline assessment) and Month 12.
次要结局
- Kaplan-Meier Estimates for Failure Rates of Efficacy Endpoints(At 12-month and 24-month after start of study drug)
- Change From Baseline in Estimated Glomerular Filtration Rate - Month 24(Baseline, Month 24)
- Growth Development - Height at Baseline and Month 12(Baseline, Month 12)
- Growth Development - Weight at Baseline and Month 12(Baseline, Month 12)
- Growth Development - Weight at Baseline and Month 24(Baseline, Month 24)
- Growth Development - Height at Baseline and Month 24(Baseline, Month 24)