A Randomised Controlled Comparison of Campath-Tacrolimus vs IL2R MoAb-Tacrolimus/Mycophenolate Mofetil in Kidney Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 123
- 试验地点
- 1
- 主要终点
- One Year Survival With a Functioning Graft
研究概览
简要总结
The advent of new, potent immunosuppressive (anti-rejection) drugs over the past ten years has substantially reduced the risk of rejection after kidney transplantation, has allowed the development of immuno-suppressive regimens that do not use long-term steroids (steroid avoidance), and has improved transplant success rates both in the short and medium term.
The main new agents used in these modern regimens are the calcineurin inhibitor (CNI) tacrolimus; the anti-proliferative agent mycophenolate; and induction agents which are used to provide effective early suppression of the rejection process; these include monoclonal antibodies (MoAb) such as IL-2 receptor blocking antibodies (IL-2R MoAb: basiliximab and daclizumab) and the anti-CD52 antibody Campath-1H (alemtuzumab).
Although almost all modern immunosuppressive regimens involve one or more of these agents, it is not known which is the safest and most effective combination.
This randomised controlled trial compares two steroid sparing regimens which have been used with very good short and medium term results at St Mary's Hospital Renal and Transplant Unit over the last 5 years. The primary hypothesis is that the alemtuzumab/tacrolimus regimen is as effective and safe as the IL-2R MoAb/tacrolimus/mycophenolate regimen.
详细描述
RECENT EXPERIENCE AT ST MARY'S:
The St Mary's Hospital Renal Unit (now combined with the Hammersmith Hospital Renal Unit at the West London Renal and Transplant Centre) introduced Tacrolimus based immunosuppression in 1995, developing a steroid avoidance regimen based on Tacrolimus, Mycophenolate, and IL-2R MoAb between 2000 and 2002, and moving to Campath-1H as an induction agent in 2004. Results over this period have been excellent with five and ten year survivals with functioning graft rates of 82% and 72% for the first 260 cadaveric kidney transplants performed since 1995.
The two most recent regimens used at St Mary's have both produced very low (< 10%) rejection rates, and very good (> 90%) short-term rejection-free patient and graft survival rates. Between 2002 and 2004, the regimen consisted of induction with an Interleukin-2 (IL2) -Receptor blocking monoclonal antibody with Tacrolimus and Mycophenolate as long term maintenance therapy. In patients without rejection steroid usage was limited to the first 7 days post-transplant. The current regimen uses Campath-1H (which is now well established as an induction agent in renal transplantation for induction), with Tacrolimus monotherapy maintenance and an identical short-course steroid regimen.
CHARACTERISTICS OF THE TWO REGIMENS TO BE COMPARED:
The IL2R MoAb/Tacrolimus/Mycophenolate/Short-course steroids regimen (2002-2004 Regimen 1) has the advantage of flexibility in terms of adjusting maintenance therapy to allow clinical response to patients and transplants with different tolerance of the two maintenance agents, but involves increased expense in terms of using and monitoring the blood levels of two modern (and hence expensive) agents. In addition, patients have long-term exposure to the anti-proliferative agent Mycophenolate, which can be associated with increased risk of infection, gastrointestinal side effects, and skin malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Kidney transplant recipients under the care of the West London Renal and Transplant Centre
排除标准
- •Patients who are unable to give written informed consent
- •Simultaneous kidney/pancreas transplant recipients
- •Non-heart beating deceased donor transplant recipients
- •Patients who would not be offered Campath-1H induction under our current protocol (patients with previous malignancy or with previous exposure to cytotoxic or antiproliferative agents)
研究组 & 干预措施
Daclizumab-Tacrolimus-Mycophenolate
Daclizumab induction with 7-day short-course steroids followed by Tacrolimus and Mycophenolate mofetil therapy
干预措施: Daclizumab (Drug)
Campath-Tacrolimus
Campath induction with 7-day short-course steroids followed by tacrolimus monotherapy
干预措施: Campath (Drug)
结局指标
主要结局
One Year Survival With a Functioning Graft
时间窗: 1 year
One year survival with a functioning graft, defined as transplant recipient remaining alive and dialysis-independent. the functioning graft is a graft still functioning at the time of analysis. Graft function was estimated using the Modification of Diet in Renal Disease four-variable formula and comparison of graft function between arms undertaken with Student'st test.
次要结局
- Initial Length of Stay in Hospital(1 year)
- Graft Function: Level of Creatinine(2 years)
- Patient Survival Censored for Death With Function(2 years)
- Occurrence of Rejection Episodes(1 year)
- Presence in the Blood of Cells Which Might Trigger Rejection in, or Promote Tolerance to the Graft(3 years)
- Graft Survival Censored for Death With Function(2 years)
- Occurrence of Significant Episodes of Infection(1 year)
- Early Development of Scarring in the Grafts(1 year)
研究者
EMagnusson
RIO
Imperial College Healthcare NHS Trust