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Hypothermic Machine Perfusion for Liver Graft Preservation (HOPE-Liver)

2026年5月14日 更新者：University of Sao Paulo General Hospital

Prospective and Randomized Clinical Study of the Effect of Hypothermic Machine Perfusion on Liver Graft Preservation

The goal of this clinical trial is to evaluate whether hypothermic machine perfusion improves liver graft preservation and post-transplant outcomes compared to conventional static cold storage in adult patients undergoing liver transplantation. This study focuses on liver grafts from deceased donors, including those with extended criteria, which are more susceptible to ischemia-reperfusion injury and early graft dysfunction.

The main questions it aims to answer are:

Does hypothermic machine perfusion reduce ischemia-reperfusion injury and improve early graft function after liver transplantation? Does this preservation strategy improve clinical outcomes, including graft survival, complication rates, and post-transplant recovery, compared to static cold storage?

Researchers will compare hypothermic machine perfusion (ex situ, oxygenated perfusion at low temperature) to standard static cold storage to assess differences in graft preservation quality and post-transplant outcomes.

Participants will:

Receive a liver graft preserved either by hypothermic machine perfusion or static cold storage, according to a 1:1 randomization protocol Undergo standard liver transplantation procedures Be followed after transplantation with clinical, laboratory, imaging, and biomarker assessments at predefined time points (7 days, 30 days, 6 months, and 1 year)

Additional evaluations will include biochemical markers of liver function, inflammatory and immunological mediators, mitochondrial function assessment, and histological analysis to better characterize graft injury and recovery.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

This is a prospective, single-center, randomized controlled clinical trial designed to evaluate the impact of hypothermic machine perfusion on liver graft preservation and post-transplant outcomes in adult liver transplantation.

Liver transplantation is the standard treatment for end-stage liver disease; however, outcomes are strongly influenced by graft quality. The increasing use of extended criteria donors has introduced additional challenges, as these grafts are more susceptible to ischemia-reperfusion injury, a key determinant of early graft dysfunction and post-transplant complications. Conventional static cold storage, although widely used, does not prevent ongoing anaerobic metabolism and progressive depletion of cellular energy stores, contributing to mitochondrial dysfunction, oxidative stress, and inflammatory activation upon reperfusion.

Hypothermic machine perfusion has emerged as an alternative preservation strategy by providing continuous oxygenated perfusion under controlled hypothermic conditions. This approach aims to preserve mitochondrial integrity, reduce metabolic stress, and mitigate ischemia-reperfusion injury, thereby potentially improving graft viability and expanding the utilization of marginal organs.

In this study, liver grafts from deceased donors will be allocated to either hypothermic machine perfusion or conventional static cold storage. Following procurement, grafts assigned to the intervention group will undergo ex situ hypothermic perfusion using an oxygenated preservation solution under controlled conditions, while the control group will follow standard institutional preservation protocols.

All transplant procedures and perioperative management will be conducted according to institutional standards. Post-transplant follow-up will include clinical and laboratory monitoring to assess graft function and detect complications.

研究类型

介入性

注册 (估计的)

40

阶段

  • 不适用

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。

学习联系方式

  • 姓名：Wellington Andraus, MD, PhD
  • 电话号码：+5511982118909
  • 邮箱：wellington@usp.br

研究联系人备份

  • 姓名：Alexandre Santana, PhD
  • 电话号码：+5511931002779
  • 邮箱：alesantana@usp.br

学习地点

  • 巴西
    • São Paulo
      • São Paulo、São Paulo、巴西、05403-000
        • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
        • 接触：
          • Wellington Andraus, MD, PhD
          • 电话号码：+5511982118909
          • 邮箱：wellington@usp.br
        • 接触：
        • 首席研究员：
          • Wellington Andraus, MD, PhD
        • 副研究员：
          • Rubens Junior, MD, PhD
        • 副研究员：
          • Alexandre Santana, PhD

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

  • 成人
  • 年长者

接受健康志愿者

不

描述

Donor-related inclusion criteria:

  • Liver donors with confirmed diagnosis of brain death.
  • Extended criteria donors (ECD).
  • Age ≥18 years.
  • Family consent for organ donation obtained.
  • Negative serology for HTLV, HIV, Chagas disease, and hepatitis B and C.

Recipient-related inclusion criteria:

  • Adult patients (≥18 years) undergoing liver transplantation.
  • Diagnosis of end-stage liver disease or indication for liver transplantation.
  • Candidates for primary liver transplantation.
  • Ability to understand and provide written informed consen

Donor-related exclusion criteria:

  • Presence of moderate or severe hepatic steatosis.
  • Pediatric donors.
  • Donors classified as ideal, defined by the simultaneous presence of all of the following criteria: Age <35 years, Body mass index (BMI) <28 kg/m², No history of cardiopulmonary resuscitation, Norepinephrine requirement <0.5 µg/kg/min, Liver enzymes (AST or ALT) ≥2 times the upper limit of normal, Intensive care unit stay ≤7 days

Recipient-related exclusion criteria:

  • Complex portal vein thrombosis (grade III or IV).
  • Combined or dual organ transplantation.
  • Retransplantation.
  • Acute liver failure.
  • MELD score >30.
  • History of multiple prior liver or biliary surgeries.

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：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Hypothermic Machine Perfusion
Liver grafts are preserved using hypothermic machine perfusion prior to transplantation. Following procurement and an initial period of static cold storage, grafts undergo ex situ hypothermic oxygenated perfusion under controlled conditions before implantation.
设备：Hypothermic Machine Perfusion
Hypothermic machine perfusion of the liver graft is performed prior to transplantation using an ex situ perfusion system under controlled conditions, in which an oxygenated perfusate is circulated through the liver graft vasculature.
有源比较器：Static Cold Storage
Liver grafts are preserved using conventional static cold storage according to standard institutional protocols. Following procurement, grafts are maintained under hypothermic conditions without active perfusion or oxygenation until implantation.
程序：Static Cold Storage
Liver graft preservation using conventional static cold storage under hypothermic conditions until transplantation.

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
Incidence of Early Allograft Dysfunction (EAD)
大体时间：Within 7 days after transplantation
Early allograft dysfunction is defined according to established clinical criteria, including at least one of the following within the first 7 days after transplantation: total bilirubin ≥10 mg/dL on day 7, international normalized ratio (INR) ≥1.6 on day 7, or alanine or aspartate aminotransferase (ALT or AST) levels >2000 IU/L within the first 7 days.
Within 7 days after transplantation

次要结果测量

结果测量
措施说明
大体时间
Change in Liver Function Tests (AST, ALT, Total Bilirubin)
大体时间：At 7 days, 30 days, 6 months, and 1 year after transplantation
Serial measurements of liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, obtained through routine laboratory testing following liver transplantation. Values will be analyzed over time to assess graft function and recovery.
At 7 days, 30 days, 6 months, and 1 year after transplantation
Incidence of Acute Kidney Injury (AKI)
大体时间：Within 7 days and up to 30 days after transplantation
Occurrence of acute kidney injury following liver transplantation, defined based on changes in serum creatinine levels according to established clinical criteria.
Within 7 days and up to 30 days after transplantation
Incidence of Post-Reperfusion Syndrome (PRS)
大体时间：During transplantation procedure
Occurrence of post-reperfusion syndrome during liver transplantation, defined as a decrease in mean arterial pressure greater than 30% from baseline within the first minutes after graft reperfusion, with or without the need for increased vasopressor support.
During transplantation procedure
Incidence of Post-Transplant Complications
大体时间：Up to 1 year after transplantation
Occurrence of post-transplant complications, including biliary complications, vascular complications, infections, and acute rejection, assessed according to standard clinical definitions and severity grading systems.
Up to 1 year after transplantation
Graft Survival
大体时间：Up to 1 year after transplantation
Survival of the transplanted liver graft without the need for retransplantation
Up to 1 year after transplantation
Patient Survival
大体时间：Up to 1 year after transplantation
Survival of the transplant recipient following liver transplantation.
Up to 1 year after transplantation
Length of Intensive Care Unit Stay
大体时间：From liver transplantation until intensive care unit discharge, up to 30 days
Duration of stay in the intensive care unit following liver transplantation.
From liver transplantation until intensive care unit discharge, up to 30 days
Length of Hospital Stay
大体时间：From liver transplantation until hospital discharge, up to 30 days
Duration of hospital stay following liver transplantation.
From liver transplantation until hospital discharge, up to 30 days

其他结果措施

结果测量
措施说明
大体时间
Analysis of Perfusate Biomarkers
大体时间：During machine perfusion and immediately prior to transplantation
Assessment of biochemical and metabolic biomarkers in perfusate samples collected during hypothermic machine perfusion, aiming to evaluate graft viability and ischemia-reperfusion injury.
During machine perfusion and immediately prior to transplantation
Assessment of Mitochondrial Function Biomarkers (Flavin Mononucleotide, FMN)
大体时间：During machine perfusion period
Measurement of mitochondrial injury and function through biomarkers such as flavin mononucleotide (FMN) in perfusate and/or biological samples, as an indicator of ischemia-reperfusion injury and graft viability.
During machine perfusion period
Assessment of Inflammatory Biomarkers
大体时间：During machine perfusion and within the first 7 days after transplantation
Evaluation of inflammatory mediators, including cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in biological samples to characterize the inflammatory response associated with transplantation and preservation strategies.
During machine perfusion and within the first 7 days after transplantation
Histological Assessment of Liver Graft Injury
大体时间：During the perioperative period, including before and after machine perfusion and prior to transplantation
Histological evaluation of liver tissue samples to assess ischemia-reperfusion injury, inflammation, and structural integrity of the graft.
During the perioperative period, including before and after machine perfusion and prior to transplantation

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。

赞助

University of Sao Paulo General Hospital

合作者

XVIVO Perfusion

调查人员

  • 首席研究员：Wellington Andraus, MD, PhD、Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
  • 学习椅：Rubens Macedo Junior, MD, PhD、Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
  • 研究主任：Alexandre Santana, PhD、Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)

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 (估计的)

2026年5月7日

初级完成 (估计的)

2027年5月7日

研究完成 (估计的)

2028年5月7日

研究注册日期

首次提交

2026年5月6日

首先提交符合 QC 标准的

2026年5月14日

首次发布 (实际的)

2026年5月19日

研究记录更新

最后更新发布 (实际的)

2026年5月19日

上次提交的符合 QC 标准的更新

2026年5月14日

最后验证

2026年5月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 7.497.991
  • 2025/08106-0 (其他赠款/资助编号：São Paulo Research Foundation (FAPESP))

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

IPD 计划说明

No final decision has been made regarding the sharing of individual participant data (IPD). The study involves clinical data and biological samples, including biomarker analyses, which require careful consideration regarding data anonymization, ethical approvals, and institutional policies. A data sharing plan may be developed in the future in accordance with applicable regulations and journal requirements.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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.

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