Calcineurin Inhibitor Minimisation in Renal Transplant Recipients With Stable Allograft Function: A Prospective Randomised Controlled Trial
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- To compare renal allograft markers of damage and evolving injury in biopsies immediately pre study and at the end of the study
研究概览
简要总结
The purpose of this trial is to ascertain whether the withdrawal of calcineurin inhibitors (CNI) will lead to less kidney transplant damage when compared with minimisation. The investigators will assess this by comparing the degree of damage on kidney biopsies taken before and after minimisation/withdrawal of CNI.
详细描述
Renal transplantation is the most effective form of treatment for end-stage renal failure. It doubles long-term survival and has major socioeconomic and health benefits compared to patients who remain on dialysis. Graft survival in the UK is 90% at one year and greater than 75% at 5 years [UKTransplant, 2004], with better survival of grafts from living donors compared with deceased. However, by 15 years post-transplantation, over 50% of recipients who are still alive have returned to dialysis. Indeed, premature allograft failure is now one of the leading causes of end stage renal disease. As short-term outcomes of renal transplantation continue to improve, increasing attention is being paid to this late attrition of renal allografts.
It is recognised that calcineurin inhibitor (CNI) nephrotoxicity is a major factor in late renal allograft failure and dysfunction. In fact, withdrawal of CNI from patients with deteriorating graft function may improve graft function. However, there is abundant evidence that histological renal allograft damage may progress even in the absence of changes in renal function - i.e. declining renal function is a late marker of renal damage, and therefore institution of therapies (including CNI minimisation) to slow this process may be "too little, too late".
CNI minimisation may be optimised by three major routes. Firstly, by minimising the CNI beyond 12 months post transplantation when the risk of acute rejection is at its greatest. Secondly, by performing a renal biopsy in patients prior to CNI minimisation and avoiding CNI minimisation in patients with inflammation on the biopsy. Finally, converting azathioprine to mycophenolate prior to CNI minimisation should have a renoprotective effect.
The type of CNI we will investigate is cyclosporine.
Patients who fulfill the study entry criteria will require a renal allograft biopsy prior to randomisation to exclude acute rejection, recurrent disease or de novo glomerulonephritis. Those patients with an acceptable biopsy will proceed to randomisation on a 1:1 basis into 2 groups:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient must be an adult recipient of a first kidney transplant
- •A functioning kidney allograft with estimated (e)GFR by MDRD > 30 ml/min/1.73 m2, and be between 1 and 5 years post transplantation
- •Stable allograft function, as defined by no greater than 10% rise in serum creatinine in the preceding 6 months, on cyclosporine and azathioprine based immunosuppression
- •Minimal proteinuria, evidenced as urine albumin: creatinine ratio < 50 mg/mmol
排除标准
- •> = 18 years of age
- •Pregnancy or suspicion of pregnancy confirmed by positive b-HCG pregnancy test
- •Female patients unwilling to take effective contraception for study duration
- •Untreated ureteric obstruction on ultrasound of allograft
- •Recurrent urosepsis
- •Severe systemic infection
- •Untreated significant (> 50%) renal artery stenosis on magnetic resonance angiography performed prior to study
- •History of acute allograft rejection
- •History of myocardial infarction
- •History of malignancy in previous 5 years (excluding non-melanomatous tumours limited to skin)
- •Symptomatic ischaemic heart disease
- •Hepatitis B surface antigen positive, Hepatitis C positive, or HIV positive
- •Recipient of combined organ transplantation (e.g. pancreas/kidney; liver/kidney)
- •Recipient of ABO-incompatible kidney
- •Greater than 1 HLA mismatch at either the "B" or "DR" locus
- •Peak HLA antibody Panel Reactivity (PRA) greater than 10%
- •Recipient who underwent HLA desensitisation procedure prior to transplantation
研究组 & 干预措施
1
CNI [Cyclosporine] minimisation Group. Conversion from azathioprine to Myfortic followed by a three month period of cyclosporine weaning to target blood level of 50-100 ng/ml.
干预措施: Cyclosporine (Drug)
2
CNI [Cyclosporine] withdrawal Group. Conversion from azathioprine to Myfortic followed by a three month period of cyclosporine weaning to the point of withdrawal.
干预措施: Cyclosporine (Drug)
结局指标
主要结局
To compare renal allograft markers of damage and evolving injury in biopsies immediately pre study and at the end of the study
时间窗: 16 months
次要结局
- To compare markers of kidney transplant function(16 months)
- To compare markers of immune function(16 months)
- Infection episodes(16 months)
- To assess changes in independent cardiovascular risk factors(16 months)
- Malignancy(16 months)
- Patient Survival(16 months)