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Safety Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction (ATG_HVH)

2020年2月11日 更新者:Cristina Dopazo Taboada、Hospital Vall d'Hebron

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

地位

完全的

研究类型

介入性

注册 (实际的)

30

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Barcelona、西班牙、08035
        • Department of HPB Surgery and Transplants, Hospital Vall d´Hebron

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 70年 (成人、年长者)

接受健康志愿者

有资格学习的性别

全部

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

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

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
无干预:Basiliximab
Historical comparable cohort treated with Basiliximab 20mg iv administered at 0 and 4th day post-transplant
有源比较器:ATeGe-Fresenius
Administered at 1 , 3, 5 and 7 day post-transplant at 2-3mg/kg with dose adjustment according to CD2/CD3 levels

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
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
Creatinine (mg/dL) and MDRD Glomerular Filtrate Rate (ml/min/1.73m2) will be measured following the time frame described above
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

次要结果测量

结果测量
措施说明
大体时间
Incidence of biopsy proven acute cellular rejection.
大体时间:Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
If liver dysfunction is detected, percutaneous liver biopsy will be performed and histological severity will be assed following BANF criteria
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
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.
Once liver dysfunction is detected and one year post-transplant by protocol.
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
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

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

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2011年10月1日

初级完成 (实际的)

2020年2月1日

研究完成 (实际的)

2020年2月1日

研究注册日期

首次提交

2011年10月11日

首先提交符合 QC 标准的

2011年10月13日

首次发布 (估计)

2011年10月17日

研究记录更新

最后更新发布 (实际的)

2020年2月12日

上次提交的符合 QC 标准的更新

2020年2月11日

最后验证

2020年2月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • ATG-IRA-HVH.10
  • 2011-000691-34 (EudraCT编号)

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

ATeGe-Fresenius的临床试验

3
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