Hypothermic Machine Perfusion for Liver Graft Preservation (HOPE-Liver)
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.
Обзор исследования
Статус
Вмешательство/лечение
Подробное описание
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.
Тип исследования
Регистрация (Оцененный)
Фаза
- Непригодный
Контакты и местонахождение
Контакты исследования
- Имя: Wellington Andraus, MD, PhD
- Номер телефона: +5511982118909
- Электронная почта: wellington@usp.br
Учебное резервное копирование контактов
- Имя: Alexandre Santana, PhD
- Номер телефона: +5511931002779
- Электронная почта: alesantana@usp.br
Места учебы
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São Paulo
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São Paulo, São Paulo, Бразилия, 05403-000
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
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Контакт:
- Wellington Andraus, MD, PhD
- Номер телефона: +5511982118909
- Электронная почта: wellington@usp.br
-
Контакт:
- Alexandre Santana, PhD
- Номер телефона: +5511931002779
- Электронная почта: alesantana@usp.br
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Главный следователь:
- Wellington Andraus, MD, PhD
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Младший исследователь:
- Rubens Junior, MD, PhD
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Младший исследователь:
- Alexandre Santana, PhD
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Описание
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.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: 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.
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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.
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Активный компаратор: 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.
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Liver graft preservation using conventional static cold storage under hypothermic conditions until transplantation.
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Incidence of Early Allograft Dysfunction (EAD)
Временное ограничение: 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.
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Within 7 days after transplantation
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Change in Liver Function Tests (AST, ALT, Total Bilirubin)
Временное ограничение: At 7 days, 30 days, 6 months, and 1 year after transplantation
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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.
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At 7 days, 30 days, 6 months, and 1 year after transplantation
|
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Incidence of Acute Kidney Injury (AKI)
Временное ограничение: Within 7 days and up to 30 days after transplantation
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Occurrence of acute kidney injury following liver transplantation, defined based on changes in serum creatinine levels according to established clinical criteria.
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Within 7 days and up to 30 days after transplantation
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Incidence of Post-Reperfusion Syndrome (PRS)
Временное ограничение: During transplantation procedure
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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.
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During transplantation procedure
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Incidence of Post-Transplant Complications
Временное ограничение: Up to 1 year after transplantation
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Occurrence of post-transplant complications, including biliary complications, vascular complications, infections, and acute rejection, assessed according to standard clinical definitions and severity grading systems.
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Up to 1 year after transplantation
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Graft Survival
Временное ограничение: Up to 1 year after transplantation
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Survival of the transplanted liver graft without the need for retransplantation
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Up to 1 year after transplantation
|
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Patient Survival
Временное ограничение: Up to 1 year after transplantation
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Survival of the transplant recipient following liver transplantation.
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Up to 1 year after transplantation
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Length of Intensive Care Unit Stay
Временное ограничение: From liver transplantation until intensive care unit discharge, up to 30 days
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Duration of stay in the intensive care unit following liver transplantation.
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From liver transplantation until intensive care unit discharge, up to 30 days
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Length of Hospital Stay
Временное ограничение: From liver transplantation until hospital discharge, up to 30 days
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Duration of hospital stay following liver transplantation.
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From liver transplantation until hospital discharge, up to 30 days
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Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Analysis of Perfusate Biomarkers
Временное ограничение: During machine perfusion and immediately prior to transplantation
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Assessment of biochemical and metabolic biomarkers in perfusate samples collected during hypothermic machine perfusion, aiming to evaluate graft viability and ischemia-reperfusion injury.
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During machine perfusion and immediately prior to transplantation
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Assessment of Mitochondrial Function Biomarkers (Flavin Mononucleotide, FMN)
Временное ограничение: During machine perfusion period
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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.
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During machine perfusion period
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Assessment of Inflammatory Biomarkers
Временное ограничение: During machine perfusion and within the first 7 days after transplantation
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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.
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During machine perfusion and within the first 7 days after transplantation
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Histological Assessment of Liver Graft Injury
Временное ограничение: During the perioperative period, including before and after machine perfusion and prior to transplantation
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Histological evaluation of liver tissue samples to assess ischemia-reperfusion injury, inflammation, and structural integrity of the graft.
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During the perioperative period, including before and after machine perfusion and prior to transplantation
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Соавторы и исследователи
Соавторы
Следователи
- Главный следователь: Wellington Andraus, MD, PhD, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
- Учебный стул: Rubens Macedo Junior, MD, PhD, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
- Директор по исследованиям: Alexandre Santana, PhD, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
Публикации и полезные ссылки
Общие публикации
- Czigany Z, Lurje I, Schmelzle M, Schoning W, Ollinger R, Raschzok N, Sauer IM, Tacke F, Strnad P, Trautwein C, Neumann UP, Fronek J, Mehrabi A, Pratschke J, Schlegel A, Lurje G. Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications. J Clin Med. 2020 Mar 20;9(3):846. doi: 10.3390/jcm9030846.
- Patrono D, Surra A, Catalano G, Rizza G, Berchialla P, Martini S, Tandoi F, Lupo F, Mirabella S, Stratta C, Salizzoni M, Romagnoli R. Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors. Sci Rep. 2019 Jun 27;9(1):9337. doi: 10.1038/s41598-019-45843-3.
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- 7.497.991
- 2025/08106-0 (Другой номер гранта/финансирования: São Paulo Research Foundation (FAPESP))
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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