Effect of Sirolimus or Mycophenolate With Tacrolimus on Survival of Pancreas and Kidney Grafts in Type 1 Diabetic Recipients After Simultaneous Pancreas and Kidney Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 238
- 试验地点
- 1
- 主要终点
- Pancreas graft survival
研究概览
简要总结
This is prospective randomized open single center clinical study to compare effect of sirolimus vs mycophenolate tacrolimus based protocol on pancreas and kidney graft survival in simultaneous pancreas and kidney recipients.
详细描述
MTOR (mammalian target of rapamycin) inhibitors represent group of immunosuppressive drugs with mechanism of T-cell blockade complementary to calcineurin inhibitors. The investigators presume that combination of sirolimus with tacrolimus will result in better survival of pancreatic and kidney grafts in simultaneous pancreas and kidney transplantations.
The study is proposed as a single-center extension of EUROSPK 002 trial originally started in 2004 by the EUROSPK Study Group. Recruitment of recipients started in 2004 with approval of EUROSPK 002. The patient recruitment has continued in a single center (Institute for Clinical and Experimental Medicine in Prague, Czech Republic) using the same inclusion and exclusion criteria. The recipients of primary kidney and pancreas transplantation have been randomized into 2 arms.
- In the intervention arm sirolimus is added to protocol at a dose of 5 mg immediately before transplantation, the dose is adjusted to maintained trough sirolimus trough levels between 5-10ng/ml.
- In the control arm mycophenolate mofetil was added to tacrolimus. Starting with 1g before transplantation, the dose has been increased to 1g bid afterwards.
Induction protocol at day 0. consists of ATG (antithymocyte globulin)induction 8mg/kg , Tacrolimus 0.05mg/kg, Methylprednisolone 125mg. Dosing of tacrolimus has been adjusted to maintain trough levels between 5-10ng/ml. ATG was administered at 3mg/kg on days 1.-3. Steroids have been gradually tapered from a dose of 20 mg prednison orally and withdrawn by 6w after transplantation.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 diabetes mellitus
- •End stage kidney failure
- •Negative CDC crossmatch
- •Female patients of childbearing age must have a negative pregnancy test
- •Patient must have signed the Patient Informed Consent Form.
- •Patient must receive a primary simultaneous pancreas/kidney (SPK) cadaver transplant,
排除标准
- •Patient is pregnant or breastfeeding.
- •Patient is allergic or intolerant to Mycophenolate Mofetil, Sirolimus, ATG, Tacrolimus
- •Patient has malignancy or history of malignancy, with the exception of adequately treated localized squamous cell or basal cell carcinoma, without recurrence.
- •Patient has been included in another clinical trial protocol for any investigational drug within 4 weeks prior to randomization.
- •Patient has any form of substance abuse or psychiatric disorder or condition, which invalidate communication.
- •Severe cardiac failure or severe liver failure diagnosed at the time of transplantation
研究组 & 干预措施
mycophenolate mofetil
mycophenolate mofetil dosing 1g before transplantation and 1g bid afterwards
干预措施: Mycophenolate Mofetil (Drug)
Sirolimus
Sirolimus oral product Dosing 5mg orally 2-6h before transplantation Target trough levels between 5-10ng/ml
干预措施: Sirolimus Oral Product (Drug)
结局指标
主要结局
Pancreas graft survival
时间窗: 10 years
Number of failed pancreatic grafts, failure is defined as graft removal, death, retransplantation or return to intensified insulin regimen.
次要结局
- Recipient survival(10 years)
- Wound healing time(1year)
- Kidney graft survival(10 years)
研究者
Frantisek Saudek
professor
Institute for Clinical and Experimental Medicine