A Multicenter, Randomized, Parallel-group, Trial to Reduce Toxicity of Calcineurininhibitor-therapy in Steroid-free Longterm Immunosuppression in Pediatric and Adolescent Kidney Transplant Recipients
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 50
- 试验地点
- 10
- 主要终点
- Mean decline per month in glomerular filtration rate (calculated acc. to Schwartz' formula) during the clinical trial - comparison between the two study arms (CSA-dose reduction group and group with constant CSA-dosing)
研究概览
简要总结
The purpose of this study is to determine if a safe reduction of cyclosporine A in pediatric and adolescent patients with stable renal graft function, reduces signs of calcineurin-inhibitor toxicity.
详细描述
Chronic transplant nephropathy is one of the major causes of graft loss after renal transplantation. Toxicity of calcineurin-inhibitors is suspected to be one cause for loss of graft function. Therefore reduction of cyclosporine A dosing can result in longer graft survival and better graft function in patients after renal-transplantation. However, reduction of immunosuppression can result in acute rejection episodes, although it is less likely in patients with stable graft function 12 months or longer after successful renal transplantation.
Therefore the aim of this randomized, controlled study in pediatric and adolescent renal transplant recipients, is to compare the impact of reduced cyclosporine A-dosing to standard CSA-dosing on renal graft function. Therapy monitoring in both groups will be performed by obtaining CSA blood levels two hours after intake, as they provide an individual insight in pharmacokinetics in comparison to conventional trough level (C0)-measurements.
Secondary objectives to evaluate are
- the evaluation of the health-related Quality of life and psychosocial burden in the two treatment arms.
- measurement of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity.
- To obtain new insights by screening for metabolites conjunct with clinic features of nephrotoxicity or graft rejections a metabolomic screening and a targeted analysis (trimethylamine-N-oxide, neopterin and kynurenine/tryptophan ratio) will be performed.
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
- None
入排标准
- 年龄范围
- 3 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age at inclusion 3-16 years
- •male or female patients
- •recipient of first or second renal transplant
- •graft age > 24 months
- •last acute rejection episode > 6 months ago
- •Immune suppression comedication Mycophenolatmofetil (MMF) in a dose range of 1200 +/- 200 mg/m² BSA/d within at least 6 months or minimal MPA-AUC ≥ 45 mg x h/l. If MPA-AUC < 45 mg x h/l adjustment of dosage with re-screening in ≥ 4 weeks is possible.
- •Application of CSA in stable dosing within the last 3 months before study inclusion and CSA-C2-level > 500 ng/ml. If CSA-C2-level < 500 ng/ml adjustment of dosage with re-screening in ≥ 4 weeks is possible.
- •steroid-free immunosuppression for at least 6 months before enrollment
- •biopsy of the renal graft without any signs of acute rejection (def. according to BANFF classification), within 3 months before enrollment
- •written informed consent of parents/legal guardians and, if applicable, patient's consent
排除标准
- •glomerular filtration rate < 40 ml/min/1.73 m2 BSA (acc. to Schwartz' formula) at time of enrollment
- •> 2 episodes of acute graft rejection within 12 months prior to enrollment
- •condition after steroid-resistant graft rejection
- •actual participation in another clinical trial
- •Recurrence of primary renal disease in the graft
- •proven infection with EBV and/ or CMV and antiviral therapy within 3 months prior to enrollment
- •proven infection with polyoma virus within 3 months prior to enrolment
- •pregnant or nursing women
- •hemoglobin < 8 g/dl at screening visit
- •non-treated arterial hypertension
- •uncontrolled infectious disease
- •history of malignancy of any organ system, treated or non-treated
研究组 & 干预措施
A
Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy).
干预措施: Reduction of cyclosporine A (CSA)-dosing (Drug)
结局指标
主要结局
Mean decline per month in glomerular filtration rate (calculated acc. to Schwartz' formula) during the clinical trial - comparison between the two study arms (CSA-dose reduction group and group with constant CSA-dosing)
时间窗: 24 months
次要结局
- Health-related Quality of life evaluation using validated questionnaires (TACQoL) to determine differences between the two study arms(24 months)
- Evaluation of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity(24 months)