Safety Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction (ATG_HVH)
Single Centre, Prospective, Open, Non Controlled, Pilot Study for Efficacy and Security Evaluation of Low Nephrotoxicity Immunosuppression, Based on the Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction
Renal dysfunction in the context of liver transplantation is a major issue, with difficult patients' management and determining a worsened prognosis.
Physiopathologically pretransplant renal dysfunction is dependent on multifactorial causes, including hypoperfusion-derived functional renal insufficiency, hepatorenal syndrome or interstitial parenchymatous insufficiency. On top, intra- or post-transplant events, including hypoperfusion or calcineurin inhibitors nephrotoxicity may aggravate this situation.
At present MELD criteria favours allocation of organs to patients suffering from renal insufficiency, so at least 30% of the investigators liver transplant patients suffer from some degree of renal impairment pretransplant.
After liver transplant impaired renal function tends to recover partially or completely, unless advanced parenchymatous lesions are significantly involved as a major cause of renal dysfunction.
In this context, calcineurin inhibitors avoiding or sparing protocols may help in the recovery from renal insufficiency, improving long-term prognosis. The use of anti-CD25 antibodies is a good option, but provides a limited antirejection prophylaxis, limiting the use of these antibodies to a reduced cohort of liver transplant patients.
Polyclonal antibodies might provide an advantage in management of liver transplant patients with renal insufficiency, without increasing acute rejection episodes of the allograft efficacy and security evaluation of low nephrotoxicity immunosuppression, based on the use of ATeGe, in liver transplant candidates with pre-transplant renal dysfunction.
The aim of this study is to evaluate the efficacy and security use of immunosuppression based on ATeGe in liver transplant recipients with pre-transplant renal dysfunction.
研究概览
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
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Barcelona、西班牙、08035
- Department of HPB Surgery and Transplants, Hospital Vall d´Hebron
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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:
- Patients with moderate pre-transplant renal dysfunction as defined serum creatinine levels higher than 1.5 mg/dl or eGFR (MDRD-4) <60ml/min.
- First liver transplant, including splits liver transplant.
- Patients aged 18-70 years
- Without a prior contraindication for protocol biopsy of allograft.
Exclusion Criteria:
- Multiorgan transplantation and/or liver transplant from DCD and/or with ABO incompatibility.
- Uncontrolled concomitant infections (including HIV seropositivity) and/or diarrhoea, vomiting or active gastric ulcer.
- Fulminant hepatic insufficiency as first indication for liver transplant
- Hemodynamic instability prior to liver transplant.
- Recipient presenting present or previous neoplasia, except for non-metastatic basal or squamous cutaneous carcinoma or localized hepatocarcinoma with diameter <5 cm or < 3 known lesions with diameter <3 cm.
- Intolerance to study medication.
- Patients having received vaccination with attenuated living vaccines within the previous 4 weeks.
- Severe leukopenia (< 1.2 X 10E9/L) and/or thrombocytopenia (< 50x10E9/L) and/or lymphocyte counts (CD2+/CD3+) less than 10 cells/µl.
- Significant comorbidity.
- Breastfeeding or female patients at fertile age without negative pregnancy test and accepting the use of reliable fertility control method.
学习计划
研究是如何设计的?
设计细节
- 主要用途:基础科学
- 分配:非随机化
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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无干预:Basiliximab
Historical comparable cohort treated with Basiliximab 20mg iv administered at 0 and 4th day post-transplant
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有源比较器:ATeGe-Fresenius
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Administered at 1 , 3, 5 and 7 day post-transplant at 2-3mg/kg with dose adjustment according to CD2/CD3 levels
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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 |
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Renal function improvement after liver transplant
大体时间:Measurement will be performed at 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th and 28th day post-transplant, and 2nd, 3rd, 6th and 12th month post-transplant
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Creatinine (mg/dL) and MDRD Glomerular Filtrate Rate (ml/min/1.73m2)
will be measured following the time frame described above
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Measurement will be performed at 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th and 28th day post-transplant, and 2nd, 3rd, 6th and 12th month post-transplant
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Incidence of biopsy proven acute cellular rejection.
大体时间:Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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If liver dysfunction is detected, percutaneous liver biopsy will be performed and histological severity will be assed following BANF criteria
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Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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Patient and graft survival rates after 12 months, causes of death and retransplant
大体时间:Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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Relationship between ATeGe doses, immunological variables (lymphocyte counts) and clinical adverse events (acute rejection,infections, HCV recurrence and de novo tumor)
大体时间:Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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Incidence and severity of HCV infection recurrence, based on clinical and histological criteria.
大体时间:Once liver dysfunction is detected and one year post-transplant by protocol.
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Once liver dysfunction is detected and one year post-transplant by protocol.
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Evaluation of metabolic complications (diabetes mellitus, arterial hypertension and dyslipidemia)
大体时间:Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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合作者和调查者
调查人员
- 首席研究员:ITXARONE BILBAO, PhD/MD、Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- 学习椅:CRISTINA DOPAZO, PhD/MD、Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- 研究主任:RAMON CHARCO, PHD/MD、Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- 学习椅:MONICA MARTINEZ, PhD/MD、Department of Inmunology, Hospital Vall d´Hebron (Barcelona, Spain)
- 学习椅:GONZALO SAPISOCHIN, PhD/MD、Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- 学习椅:JOSE L LAZARO, MD、Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- 学习椅:HELENA ALLENDE, PhD/MD、Department of Histology, Hospital Vall d´Hebron (Barcelona, Spain)
出版物和有用的链接
一般刊物
- Uemura T, Schaefer E, Hollenbeak CS, Khan A, Kadry Z. Outcome of induction immunosuppression for liver transplantation comparing anti-thymocyte globulin, daclizumab, and corticosteroid. Transpl Int. 2011 Jul;24(7):640-50. doi: 10.1111/j.1432-2277.2011.01250.x. Epub 2011 Mar 23.
- Benitez CE, Puig-Pey I, Lopez M, Martinez-Llordella M, Lozano JJ, Bohne F, Londono MC, Garcia-Valdecasas JC, Bruguera M, Navasa M, Rimola A, Sanchez-Fueyo A. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation. Am J Transplant. 2010 Oct;10(10):2296-304. doi: 10.1111/j.1600-6143.2010.03164.x.
- Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, Muhlbacher F, Berlakovich GA. Short-term induction therapy with anti-thymocyte globulin and delayed use of calcineurin inhibitors in orthotopic liver transplantation. Liver Transpl. 2007 Jul;13(7):1039-44. doi: 10.1002/lt.21185.
- Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, Muhlbacher F, Berlakovich GA. Short-term versus long-term induction therapy with antithymocyte globulin in orthotopic liver transplantation. Transpl Int. 2007 May;20(5):447-52. doi: 10.1111/j.1432-2277.2007.00463.x. Epub 2007 Mar 2.
- Kim MJ, Tsinalis D, Franz S, Binet I, Gurke L, Mihatsch MJ, Steiger J, Thiel G, Dickenmann M. ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial. Ann Transplant. 2008;13(4):21-7.
- Bajjoka I, Hsaiky L, Brown K, Abouljoud M. Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors. Liver Transpl. 2008 Jan;14(1):66-72. doi: 10.1002/lt.21309.
- Tector AJ, Fridell JA, Mangus RS, Shah A, Milgrom M, Kwo P, Chalasani N, Yoo H, Rouch D, Liangpunsakul S, Herring S, Lumeng L. Promising early results with immunosuppression using rabbit anti-thymocyte globulin and steroids with delayed introduction of tacrolimus in adult liver transplant recipients. Liver Transpl. 2004 Mar;10(3):404-7. doi: 10.1002/lt.20085.
- Dopazo C, Charco R, Caralt M, Pando E, Lazaro JL, Gomez-Gavara C, Castells L, Bilbao I. Low Total Dose of Anti-Human T-Lymphocyte Globulin (ATG) Guarantees a Good Glomerular Filtration Rate after Liver Transplant in Recipients with Pretransplant Renal Dysfunction. Can J Gastroenterol Hepatol. 2018 Aug 16;2018:1672621. doi: 10.1155/2018/1672621. eCollection 2018.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
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 (实际的)
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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ATeGe-Fresenius的临床试验
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Kyungpook National University HospitalMinistry of Health & Welfare, Korea; Fresenius Medical Care Korea完全的