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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Wellington Andraus, MD, PhD
- 電話番号：+5511982118909
- メール：wellington@usp.br
研究連絡先のバックアップ
- 名前：Alexandre Santana, PhD
- 電話番号：+5511931002779
- メール：alesantana@usp.br
研究場所
-
-
São Paulo
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São Paulo、São Paulo、ブラジル、05403-000
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
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コンタクト：
- Wellington Andraus, MD, PhD
- 電話番号：+5511982118909
- メール：wellington@usp.br
-
コンタクト：
- Alexandre Santana, PhD
- 電話番号：+5511931002779
- メール：alesantana@usp.br
-
主任研究者：
- Wellington Andraus, MD, PhD
-
副調査官：
- Rubens Junior, MD, PhD
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副調査官：
- Alexandre Santana, PhD
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
|
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.
|
|
アクティブコンパレータ：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of Early Allograft Dysfunction (EAD)
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Liver Function Tests (AST, ALT, Total Bilirubin)
時間枠：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.
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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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Analysis of Perfusate Biomarkers
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
協力者
捜査官
- 主任研究者：Wellington Andraus, MD, PhD、Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
- スタディチェア：Rubens Macedo Junior, MD, PhD、Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
- スタディディレクター：Alexandre Santana, PhD、Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 7.497.991
- 2025/08106-0 (その他の助成金/資金番号：São Paulo Research Foundation (FAPESP))
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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