The Effect of Intravenous Iron Therapy and Erythropoiesis-stimulation Agent Combination on Renal Transplant Outcomes
RBC transfusion (RBCT) after kidney transplantation(KT) is about 50%. Anemia is common after kidney transplant surgery due to intraoperative blood loss, delayed graft function, and side effects of immunosuppressive drugs. However, due to exposure to non-self human leukocyte antigens (HLA) from blood transfusion, there is a risk of sensitization to HLA through the production of anti-HLA antibodies. In renal transplant patients, exposure to non-self HLA antigens due to RBCT can lead to the generation of donor-specific antibodies (DSA) against renal allograft donors. Patients who have undergone KT are frequently exposed to RBCT, and immunologic damage resulting from this can be an important cause of loss of graft kidney function. Therefore, there should be a more careful review of the risk associated with RBCT on KT recipients.
Of the 16,191 Koreans who underwent KT between 2008 and 2017, 59.7% received transplant-related blood transfusions. As a result of analyzing 13,871 Koreans who underwent KT between 2007 and 2015, the overall graft failure rate was 15.5%, and the hazard ratio of survival rate according to RBCT before and after KT increased as the amount of transfusion increased. RBCT before and after KT was independently associated with graft failure and death. Therefore, research on treatment methods that can effectively reduce blood transfusion in transplant patients is absolutely necessary. About 30-60% of patients undergoing major surgery show preoperative anemia, which causes blood transfusions, complications during hospitalization, prolonged hospitalization, and delayed recovery. The most common cause of anemia is iron deficiency. In particular, an increase in hepcidin, a major regulator of iron metabolism, reduces intestinal iron absorption and promotes iron sequestering by macrophages, resulting in a state of functional iron deficiency. Therefore, oral iron intake as a treatment for anemia in surgical patients is not effective. Although the safety and clinical superiority of high-dose intravenous iron therapy have been demonstrated in patients with chronic renal failure, the effect of this drug on blood transfusion of pre- and post-kidney transplant surgery has not been studied. Therefore, this study aims to verify the effectiveness and stability of the combined administration of intravenous(IV) iron and erythropoiesis-stimulating agents(ESA) before and after KT for patients who perform KT for end-stage kidney disease(ESKD). The investigators will analyze hemoglobin, transferrin saturation, ferritin changes, and transfusion requirements according to the combined administration of IV iron and ESA before and after surgery of kidney transplant patients. Also, the investigators evaluate whether a treatment combining IV iron and ESA will be possible as an alternative blood transfusion treatment and its effect on the clinical prognosis of KT recipients. In particular, the effect on the function of the graft kidney, immunological outcomes-DSA, antibody-mediated rejection, and survival rate will be analyzed. Also, the investigators will analyze the change in expression of hepcidin and oxidative stress markers before and after kidney transplantation and the mechanism of expression according to the combined administration of IV iron and ESA. This study is a multicenter(including 3 centers), open-label, prospective, and randomized clinical trial. 302 patients undergoing living-donor KT for ESKD are randomly assigned in a 1:1 ratio to an experimental group actively using IV iron and ESA, and a control group receiving conventional anemia treatment for 42 months from the time of IRB approval. Participants selected for the experimental group will be given a total of 1000 mg of IV Monofer(iron isomaltoside); each 200 mg dose on 28, 21, and 7 days before kidney transplantation, on the day of surgery, and 7 days after surgery. In the case of ESA, it is freely used according to the criteria up to 7 days before transplantation and subcutaneously injected with 120 mcg of Mircera(methoxy polyethylene glycol-epoetin beta) between 7 days before surgery and a day before surgery. In the control group, IV Monofer is administered only 28 days before surgery according to the set criteria. Mircera is also freely used in the control group according to the criteria up to 7 days before KT but not used between 7 days before surgery and a day before surgery.
研究概览
详细说明
Total 302 subjects, Experimental group vs Control group, 1. Experimental group :
Total of 1000 mg Monofer(iron isomaltoside) IV injection; each Monofer 200mg dose on ①28, ②21, and ③7 days before KT,
- on the day of surgery, and ⑤7 days after surgery
Mircera(methoxy polyethylene glycol-epoetin beta) 120mcg SQ once : between 7 days before surgery and a day before surgery.
* In the case of ESA, it is freely used according to the criteria up to 7 days before transplantation
2. Control group :at 28 days before KT, Monofer is administered according the following criteria.
- Ferritin <100 μg/L & TSAT<20% : Monofer 200mg IV, twice
- Ferritin 100~200 μg/L & TSAT<20% : Monofer 200mg IV, once
- Ferritin 201~500 μg/L & TSAT<20% : Monofer 100mg IV, once
- Not administer in other cases * In the case of ESA, it is freely used according to the criteria up to 7 days before transplantation
研究类型
注册 (预期的)
阶段
- 第四阶段
联系人和位置
学习联系方式
- 姓名:Kyu ha Huh
- 电话号码:82-2-2228-2111
- 邮箱:khhuh@yuhs.ac
学习地点
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Seoul、大韩民国
- Yonsei University Health System, Severance Hospital
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接触:
- Kyu ha Huh
- 电话号码:82-2-2228-2111
- 邮箱:khhuh@yuhs.ac
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- living donor transplantation (age>19)
- Ferritin<700㎍/L, TSAT<40%
Exclusion Criteria:
- CDC(+), FXM(+)
- Active infection
- Hematologic malignancy, monoclonal gammaglobulin Dz, Hematologic Dz induced anemia
- Receiving treatment of malignant tumor
- HIV (+)
- ALT, AST > 3 times upper limit of normal
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:平行线
- 屏蔽:没有任何
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:实验性的
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Monofer 200mg : OP-28day, OP-21day, OP-7day, OP day, POD #7 IV injection, Mircera 120mcg SQ : OP-7 day~OP-1day
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其他:control
Follow the criteria for investigational product
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Ferritin<100, TSAT<20 : Monofer 200mg IV, twice/ Ferritin 100~200, TSAT<20 : Monofer 200mg IV, once / Ferritin 201~500, TSAT<20 : Monofer 100mg IV, once / Not administer in any other case
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
围手术期静脉铁剂联合EPO药物输血次数比较
大体时间:手术前1个月至手术后1年(手术前28天、手术后第1天、第10天、第1个月、第12个月)
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静脉铁剂联合EPO剂围手术期输血(浓缩红细胞输注)次数比较
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手术前1个月至手术后1年(手术前28天、手术后第1天、第10天、第1个月、第12个月)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
comparison of changes in anemia parameters(ferritin in ng/mL)
大体时间:From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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comparison of changes in anemia parameters(ferritin in ng/mL)
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From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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comparison of changes in anemia parameters(TSAT in %)
大体时间:From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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comparison of changes in anemia parameters(TSAT in %)
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From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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comparison of changes in anemia parameters(EPO level in mU/mL)
大体时间:From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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comparison of changes in anemia parameters(EPO level in mU/mL)
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From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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comparison of changes in hepcidin expression level in pg/mL
大体时间:手术前1个月至手术后1年(手术前28天、手术后第1天、第10天、第1个月、第12个月)
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以 pg/mL 为单位的 hepcidin 表达水平变化比较
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手术前1个月至手术后1年(手术前28天、手术后第1天、第10天、第1个月、第12个月)
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comparison of changes in oxidative stress marker
大体时间:From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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comparison of changes in oxidative stress marker(MDA in mmol/L, 4-HNE in pg/mL, NGAL in ng/mL)
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From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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comparison of changes in immunologic parameters following the administration of intravenous iron therapy and EPO agent
大体时间:From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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静脉内铁剂治疗和 EPO 剂给药后免疫学参数变化的比较(MFI 中的新发 DSA、抗体介导的排斥反应率(%)、死亡截尾移植物存活率和患者存活率(%))
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From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)
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合作者和调查者
调查人员
- 首席研究员:Kyu ha huh、Severance Hospital
研究记录日期
研究主要日期
学习开始 (预期的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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Monofer(实验)的临床试验
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Pharmacosmos A/SClinSmart完全的
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Turkiye Yuksek Ihtisas Education and Research Hospital完全的