Multicenter, Prospective, Randomized Study Investigating the Efficacy and Safety of a Reduced Immunosuppressive Therapy With Tacrolimus Once Daily in Comparison to Standard Triple Immunosuppression in Senior Renal Transplant Recipients
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 400
- 主要终点
- Combined efficacy endpoint (BPAR, graft loss and death)
研究概览
简要总结
Study purpose To establish efficacy and safety of a reduced immunosuppressive therapy with tacrolimus once daily for senior (>65 years of age) renal transplant recipients
详细描述
Study outline Stable senior transplant recipients (>65 years of age) participating in the European SENIOR transplant registry may enter the trial at month 3 post-transplant, if they fulfil all of the in- and none of the exclusion criteria. At this time patients will be randomized 1:1 either to continue
Reference therapy:
Tacrolimus once daily (Advagraf®) Mycophenolate (either MMF ≥1g/d or EC-MPS ≥720g/d) Steroids (≥5mg prednisolone or equivalent) or to Investigational therapy: Tacrolimus once daily (Advagraf®) Steroid stop at month 3 (tapering within 2 weeks) Mycophenolate stop at month 6
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 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females, aged ≥65 years and participating in the European SENIOR transplant registry
- •Patients who received a renal allograft 3 - 3.5 months prior to randomization.
- •Patient must have received primary or secondary renal allograft from a blood group compatible donor
- •Standard criteria donors (SCD), expanded criteria donors (ECD), donors after cardiac death (DCD) and living donors (LD) are eligible
- •Patients who are willing and able to participate in the study and from whom written informed consent has been obtained
- •Patients on continuous standard triple therapy with tacrolimus once daily (Advagraf, trough level ≥5ng/ml) in combination with mycophenolate (either ≥1.0g/day MMF or ≥720mg/d EC-MPS) and steroids (≥5mg prednisolone or equivalent) since transplantation
- •Stable graft function with serum creatinine ≤2.5 mg/dl.
- •Patients with low to standard immunological risk, who had a PRA over 20% and no known donor specific antibodies (DSA) at transplantation
排除标准
- •Patient with mental dysfunction or inability to comply with the study protocol
- •Patients, who - according to the investigator - require for medical reasons (e.g. previous rejections) continuous triple therapy or a different tacrolimus exposure
- •Multi-organ recipients (other solid organ (e.g. pancreas) or bone marrow)
- •Blood group ABO-incompatible allografts
- •Patients who suffered from severe T-cell mediated rejection (over Banff II acute rejection), recurrent acute rejection (>1 episode), or steroid resistant rejection post-transplant
- •History of antibody-mediated rejection (acute or chronic)
- •History of rejection 2 months prior to inclusion
- •Documented presence of donor specific antibodies (DSA) according to local lab results at baseline
- •Panel reactive antibody (PRA) >20% prior to transplantation, measured according to local standard
- •Patients receiving or having received Sirolimus, Everolimus, Azathioprine, Belatacept or Cyclophosphamide within 3 months prior to enrolment
- •Patients having received any other induction therapy than Basiliximab (e.g. depleting polyclonal antithymocyte antibodies (ATG), OKT3, Alemtuzumab)
- •Patients with proteinuria >1.0 g/day (or >1.0 g/g creatinine) at screening or having experienced nephrotic syndrome due to recurrence of focal segmental glomerulosclerosis (FSGS)
- •History of alcohol or drug abuse with less than 6 months of sobriety
- •Patient with a known hereditary immunodeficiency
- •Patient with active malignancy posttransplant with the exception of local, non-invasive, fully excised, cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ
- •Patients with clinically symptomatic congestive heart failure or symptomatic coronary artery disease
- •Patients with documented (either by serology and/or nuclear acid testing (NAT) clinically active infections (e.g. with a known Hepatitis B, Hepatitis C, HIV, CMV or BK virus infection)
- •Participation in any other investigational clinical trial 3 months before participation in this study, except the SENIOR transplant registry
- •Patients with leukopenia (<2500 cells/nl) or neutropenia (<1500 cells/nl)
- •Patients with thrombocytopenia (<100 cells/nl)
- •Patients with liver transaminases or bilirubin values > 3x normal values
- •Any significant diseases or clinically significant findings, including psychiatric and behavioural problems, medical history and/or physical examination findings that would in the opinion of the investigator preclude the patient from participating in the study.
- •Patients who have been institutionalized by official or court order
研究组 & 干预措施
Standard immunosuppression
starting immunosuppression: tacrolimus (Advagraf) (target trough levels >5 ng/ml), mycophenolate mofetil >1g/d in MMF or >720 mg/d in mycophenolic acid, steroids from month 1-3 dosing according to local practice; 200 pts are planned to carry on with standard immunosuppression (tacrolimus (Advagraf), Mycophenolate, steroids) as stated above according to international guidelines for kidney transplant recipients from month 3 posttransplant to month 12 posttransplant
干预措施: Tacrolimus (Drug)
Standard immunosuppression
starting immunosuppression: tacrolimus (Advagraf) (target trough levels >5 ng/ml), mycophenolate mofetil >1g/d in MMF or >720 mg/d in mycophenolic acid, steroids from month 1-3 dosing according to local practice; 200 pts are planned to carry on with standard immunosuppression (tacrolimus (Advagraf), Mycophenolate, steroids) as stated above according to international guidelines for kidney transplant recipients from month 3 posttransplant to month 12 posttransplant
干预措施: mycophenolate (Drug)
Standard immunosuppression
starting immunosuppression: tacrolimus (Advagraf) (target trough levels >5 ng/ml), mycophenolate mofetil >1g/d in MMF or >720 mg/d in mycophenolic acid, steroids from month 1-3 dosing according to local practice; 200 pts are planned to carry on with standard immunosuppression (tacrolimus (Advagraf), Mycophenolate, steroids) as stated above according to international guidelines for kidney transplant recipients from month 3 posttransplant to month 12 posttransplant
干预措施: Steroids (Drug)
Reduced immunosuppression
The Intervention is stopping medication:
200 pts are planned to receive a reduced immunosuppression after month 3: carry on with tacrolimus (Advagraf; trough levels >5 ng/ml) steroids stop at month 3 mycophenolate stop at month 6
干预措施: Reduced immunosuppression (Other)
Reduced immunosuppression
The Intervention is stopping medication:
200 pts are planned to receive a reduced immunosuppression after month 3: carry on with tacrolimus (Advagraf; trough levels >5 ng/ml) steroids stop at month 3 mycophenolate stop at month 6
干预措施: Tacrolimus (Drug)
Reduced immunosuppression
The Intervention is stopping medication:
200 pts are planned to receive a reduced immunosuppression after month 3: carry on with tacrolimus (Advagraf; trough levels >5 ng/ml) steroids stop at month 3 mycophenolate stop at month 6
干预措施: mycophenolate (Drug)
结局指标
主要结局
Combined efficacy endpoint (BPAR, graft loss and death)
时间窗: between randomization and month 12 posttransplant (month 9 of the study)
BPAR (biopsy proven acute rejection)
次要结局
- Number of severe infections(between randomization and month 12 posttransplant)
- Number of opportunistic infections(between randomization and month 12 posttransplant)
- Number of hospitalisations and days of hospitalisation(between randomization and month 12 posttransplant)
- Graft function by calculated glomarular filtration rate calculated by CKD-EPI(between randomization and month 12 posttransplant)
- Number of occurrences and types of donor specific antibodies (DSA)(between randomization and month 12 posttransplant)
研究者
Klemens Budde
Prof. Dr.
Charite University, Berlin, Germany