Open Label Multicenter Randomized Trial Comparing Standard Immunosuppression With Tacrolimus and Mycophenolate Mofetil With a Low Exposure Tacrolimus Regimen in Combination With Everolimus in de Novo Renal Transplantation in Elderly Patient
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 374
- 试验地点
- 7
- 主要终点
- successful transplantation
研究概览
简要总结
Open label, randomized, multicenter, intervention trial comparing standard immunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen in combination with everolimus.
The primary objective is to test the hypothesis that an age-adapted immunosuppressive regimen targeted at reduced immunosuppression with low calcineurin inhibitor (tacrolimus) exposure in combination with everolimus will result in improved outcome in elderly recipients of A: Kidneys from older deceased donors (>64 years) and B: Kidneys from living donors (all ages) and younger deceased donors (<65 years).
详细描述
In this study two immunosuppressive regimes will be tested; In both groups basiliximab induction will be applied. Additionally, the standard therapy consisting of prednisolone, mycophenolic acid and tacrolimus once-daily (Envarsus®), or the comparator in which mycophenolic acid will be replaced by everolimus combined with strongly reduced levels of tacrolimus once-daily (Envarsus®). When not tolerated,tacrolimus may be replaced by ciclosporin. The hypothesis is that reduced calcineurin inhibitor (CNI) exposure in combination with everolimus will lead to improved allograft function, a reduced incidence of complications and improved quality of life.
This study will consist of two strata: Stratum A: Elderly recipients (≥65 years) of kidneys from elderly deceased donors (≥65 years) within the Eurotransplant Senior Program. Stratum B: Elderly recipients (≥65 years) of kidneys from living donors (all ages) or deceased donors (<65 years). The primary endpoint will be "successful transplantation" which is defined as survival with a functioning allograft with a minimum estimated GFR of 30 ml/min per 1.73 m2 in stratum A and 45 ml/min per 1.73 m2 in stratum B, after 2 years.
The study will be performed by the Dutch transplant centers and the Dutch Kidney Patient Organization (NVN) will participate.
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
- 65 Years 至 99 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed
- •Male or female subject ≥65 years old
- •Subject randomized within 24 hours of completion of transplant surgery
- •Stratum A: Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased donor aged 65 years or older
- •Stratum B: Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased donor aged below 65 years or a living donor of any age
排除标准
- •Exclusion criteria for both stratum A and B
- •Subject is a multi-organ transplant recipient
- •Recipient of bloodgroup ABO incompatible allograft or CDC cross-match positive transplant
- •Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity
- •Recipient of a kidney with a cold ischaemia time (CIT) >24 hr
- •Recipients of a kidney from an HLA-identical related living donor
- •Known intolerability for one or more of the study drugs
- •Subject who is HIV positive
- •HBsAg and/or a HCV positive subject with evidence of elevated liver function tests (ALT/AST levels ≥2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable
- •Recipient of a kidney from a donor who tests positive for human immunodeficiency virus, (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV)
- •Subject with severe systemic infections, current or within the two weeks prior to randomization
- •Subject with severe restrictive or obstructive pulmonary disorders
- •Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled
- •Subject with white blood cell (WBC) count ≤ 2,000/mm3 or with platelet count ≤ 50,000/mm3
研究组 & 干预措施
group 1
standard tacrolimus with mycophenolate mofetil
干预措施: standard dose tacrolimus with mycophenolate mofetil (Drug)
group 2
low dose tacrolimus with everolimus
干预措施: low dose tacrolimus in combination with everolimus (Drug)
结局指标
主要结局
successful transplantation
时间窗: 24 months
The overall primary study endpoint "successful transplantation" as defined for the individual strata and analyzed for the whole study population. Stratum A: Primary endpoint: successful transplantation at two years after transplantation defined as: absence of graft or patient loss in the presence of an eGFR above 30 ml/min/1.73m2. Stratum B: Primary endpoint: successful transplantation at two years after transplantation defined as absence of graft or patient loss in the presence of an eGFR above 45 ml/min/1.73m2
次要结局
- death(24 months)
- graft loss(24 months)
- eGFR(12 and 24 months)
- acute rejection(24 months)
- type of rejection treatment(24 months)
- The evolution of renal function (eGFR) and creatinine clearance over time by slope analysis(24 months)
- The incidence of adverse events, serious adverse events and adverse reactions(24 months)
- The incidence of clinically relevant infections, post transplantation diabetes mellitus, malignancies and cardiovascular events(24 months)
- Presence of frailty after transplantation and change in frailty from baseline frailty from baseline(12 and 24 months)
- Physical functioning and changes over time(24 months)
- Cognitive functioning and changes over time(24 months)
- Presence of T-cell immunosenescence at 12 and 24 months and changes from baseline(24 months)
- HRQoL at 0, 12 and 24 months and changes from baseline(24 months)
- Development of donor-specific anti-HLA antibodies (DSA)(24 months)
- Difference in illness perception at 0, 12 and 24 months and changes from baseline(24 months)
- Difference in adherence of immunosuppressive medication at 12 and 24 months(24 months)
- Difference in symptoms at 0, 12 and 24 months and changes from baseline(24 months)
- Difference in iBOX predicted outcome at 3, 5 and 7 years(24 months)
- Development of a pharmacokinetic model for tacrolimus once-daily (Envarsus®), using data on AUC's(24 months)
- o evaluate the response to the COIVD-19 vaccine and identify possible differences between both treatment groups at the University Medical Center Groningen.(24 months)
研究者
J.S.F. Sanders
principal investigator, head of renal transplant program UMCG
University Medical Center Groningen