A 24 Month, Multicenter, Randomized, Open-label Safety and Efficacy Study of Concentration-controlled Everolimus With Reduced Calcineurin Inhibitor vs Mycophenolate With Standard Calcineurin Inhibitor in de Novo Renal Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 2,037
- 试验地点
- 1
- 主要终点
- Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2.
研究概览
简要总结
This is a 2-year, randomized, multicenter, open-label, 2-arm study evaluating the graft function of everolimus and reduced CNI versus MPA and standard CNI in adult de novo renal transplant recipients.
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
- •Written informed consent obtained.
- •Subject randomized within 24 hr of completion of transplant surgery.
- •Recipient of a kidney with a cold ischemia time < 30 hours.
- •Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased heart beating, living unrelated, living related non-human leukocyte antigen identical or an expanded criteria donor.
排除标准
- •Subject unable to tolerate oral medication at time of randomization.
- •Use of other investigational drugs at the time of enrollment.
- •History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
- •Multi-organ transplant recipient.
- •Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.
- •Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA.
- •Subject who is HIV-positive.
- •HBsAg and/or a HCV positive subject with evidence of elevated LFTs (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 a BMI greater than
- •Subject with severe systemic infections, current or within the two weeks prior to randomization.
- •Subject requiring systemic anticoagulation.
- •History of malignancy of any organ system.
- •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 /mm
- •Pregnant or nursing (lactating) women.
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
研究组 & 干预措施
EVR+rCNI
Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)
干预措施: Induction therapy (Biological)
EVR+rCNI
Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)
干预措施: Corticosteroids (Drug)
EVR+rCNI
Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)
干预措施: EVR+rCNI (Drug)
MPA+sCNI
Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
干预措施: Induction therapy (Biological)
MPA+sCNI
Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
干预措施: Corticosteroids (Drug)
MPA+sCNI
Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
干预措施: MPA+sCNI (Drug)
结局指标
主要结局
Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2.
时间窗: Month 12 is Primary, Month 24 secondary
Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73m2.
次要结局
- Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection(Month 12 and 24)
- Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death(Month 12 and 24)
- Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2(Month 12 and 24)
- Incidence of Failure on the Composite Endpoint of Graft Loss or Death.(Month 12 and 24)
- Incidence of eGFR < 50 mL/Min/1.73m2(Month 12 and 24)
- Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR(Baseline (week 4), Month 12 and 24)
- Evolution of Renal Function, as eGFR, Over Time by Slope Analysis.(Month 12 and 24)
- Renal Function Assessed by Creatinine Lab Values(Month 12 and 24)
- Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios.(Baseline, Month 12 and 24)
- Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported(Month 12 and 24)
- Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation.(Month 24)
- Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events.(Month 24)
- Incidence of Malignancies.(Month 24)
- Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects.(Month 12 and 24)
- Incidence of Major Cardiovascular Events.(Month 24)
- Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections(Month 12 and 24)
- Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup(Month 12 and 24)
- Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2(Month 12 and 24)
- Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up(Month 12 and 24)
- Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants)(Month 12 and 24)
- Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events)(Month 12 and 24)