Prospective Randomized Study to Characterize Risk Factors of Polyomavirus-related Transplant Nephropathy and the Impact of Three Immunosuppressive Regimens on Nephropathy Incidence
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- incidence of polyoma viremia
研究概览
简要总结
The aim of this study is to characterize and evaluate risk factors of polyomavirus nephropathy (PVN) including the impact of three immunosuppressive regimens.
详细描述
Polyomavirus nephropathy (PVN) is an emerging cause of renal transplant loss. Until now the risk factors of PVN are poorly understood. Tacrolimus (Tacr) and mycophenolate mofetil (MMF) are thought to be associated with a higher risk of developing PVN. However, the way in which Tacr or MMF might enhance the susceptibility for PVN remains largely unknown. In this prospective study we will analyze whether differences in immune-reactivity patterns (Th1, Th2, B cell and monocyte responses, sCD30, immunoregulatory antibodies) of renal transplant patients induced by different immunosuppressive regimens (cyclosporine A [CsA]/MMF, Tacr/MMF, Tacr/MMF with conversion to Tacr/Everolimus [ERL]) or by cytokine promoter gene polymorphisms may account for the different risks of developing PVN.
Comparison(s): renal transplant recipients stratified according to their relative immunological risk (group 1: low risk (primary recipients without pre-immunization [PRA < 5%]); group 2: moderate risk (group 2a: primary recipients with low pre-immunization [PRA 6-20%]; group 2b: re-transplanted patients); group 3: very high risk (re-transplanted patients with a history of vascular rejection or recipients of a first graft with high pre-immunization [PRA > 20%]) randomized to be treated with one of three immunosuppressive regimens (CsA/MMF, Tacr/MMF, Tacr/MMF with subsequent conversion to Tacr/ERL).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cadaver kidney and living donor kidney transplant recipients
- •Primary, secondary, and tertiary transplant recipients
- •Pre-immunized and not pre-immunized transplant recipients
- •Age > 18 years
排除标准
- •Contraindications against administration of one of the four study drugs
- •History of severe gastrointestinal morbidity
- •Age < 18 years
- •Pregnant or breast feeding women
- •Rejection of effective contraceptive methods with young women
- •Combined kidney and islet cell transplantation
研究组 & 干预措施
1
Immunosuppression with Ciclosporin and Mycophenolate-mofetil; Ciclosporin treatment being started at the latest at day 4 after transplantation with 7 mg/kg body weight daily administered every 8 hours until the target trough level of 300 µg/l was reached. Then it was administered twice daily with daily monitoring of trough levels. The target trough level was lowered to 200 µg/l 1 month after transplantation. Thereafter dosage and target trough levels were adjusted at the investigators discretion. Mycophenolate-mofetil was started previous to transplantation procedure with a starting dosage of 3 g/day administered twice daily. Once ciclosporin was entered into the therapy-scheme Mycophenolate-mofetil dosage was reduced to 2 g/daily. The therapy was controlled by measuring of trough levels with a target trough level exceeding 1 µg/ml. The dosage was adjusted at the investigators discretion.
干预措施: Ciclosporin and Mycophenolate-mofetil (Drug)
2
Immunosuppression with Tacrolimus and Mycophenolate-mofetil Mycophenolate-mofetil was started previous to transplantation procedure with a starting dosage of 3 g/day administered twice daily. Once tacrolimus was entered into the therapy-scheme Mycophenolate-mofetil dosage was reduced to 2 g/daily. The therapy was controlled by measuring of trough levels with a target trough level exceeding 1 µg/ml. The dosage was adjusted to clinical signs of overimmunosuppression (infections) or intolerance (mainly gastrointestinal side effects) or rejections.
干预措施: Tacrolimus and Mycophenolate-mofetil (Drug)
3
Immunosuppression with Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus after completion of posttransplant wound healing
干预措施: Tacrolimus and Mycophenolate-mofetil with change from Mycophenolate-mofetil to Everolimus (Drug)
结局指标
主要结局
incidence of polyoma viremia
时间窗: 2 years posttransplant
incidence of polyomavirus associated transplant nephropathy (PVN)
时间窗: 2 years posttransplant
urine polyomavirus concentration within the first two years post-transplant
时间窗: 2 years posttransplant
次要结局
- side effects of immunosuppressive drugs(2 years posttransplant)
- transplant function 1 and 2 years post-transplant(2 years posttransplant)
- patients' and grafts' survival(2 years posttransplant)
- incidence of acute rejections(2 years posttransplant)
- predictive value of immune parameters prognostically relevant for acute or chronic rejection(2 years posttransplant)
- comparison of urine cytology and polymerase chain reaction (PCR) quantitative data regarding diagnosis of PVN(2 years posttransplant)
研究者
Prof. Dr. Rolf Weimer
Prof. Dr.
University of Giessen