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

14. maj 2026 opdateret af: 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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

40

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

  • Navn: Wellington Andraus, MD, PhD
  • Telefonnummer: +5511982118909
  • E-mail: wellington@usp.br

Undersøgelse Kontakt Backup

  • Navn: Alexandre Santana, PhD
  • Telefonnummer: +5511931002779
  • E-mail: alesantana@usp.br

Studiesteder

  • Brasilien
    • São Paulo
      • São Paulo, São Paulo, Brasilien, 05403-000
        • Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo (Hc-Fmusp)
        • Kontakt:
          • Wellington Andraus, MD, PhD
          • Telefonnummer: +5511982118909
          • E-mail: wellington@usp.br
        • Kontakt:
        • Ledende efterforsker:
          • Wellington Andraus, MD, PhD
        • Underforsker:
          • Rubens Junior, MD, PhD
        • Underforsker:
          • Alexandre Santana, PhD

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Enhed: 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.
Aktiv komparator: 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.
Procedure: Static Cold Storage
Liver graft preservation using conventional static cold storage under hypothermic conditions until transplantation.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence of Early Allograft Dysfunction (EAD)
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in Liver Function Tests (AST, ALT, Total Bilirubin)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Analysis of Perfusate Biomarkers
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Sao Paulo General Hospital

Samarbejdspartnere

XVIVO Perfusion

Efterforskere

  • Ledende efterforsker: Wellington Andraus, MD, PhD, Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo (Hc-Fmusp)
  • Studiestol: Rubens Macedo Junior, MD, PhD, Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo (Hc-Fmusp)
  • Studieleder: Alexandre Santana, PhD, Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo (Hc-Fmusp)

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

7. maj 2026

Primær færdiggørelse (Anslået)

7. maj 2027

Studieafslutning (Anslået)

7. maj 2028

Datoer for studieregistrering

Først indsendt

6. maj 2026

Først indsendt, der opfyldte QC-kriterier

14. maj 2026

Først opslået (Faktiske)

19. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

19. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

14. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 7.497.991
  • 2025/08106-0 (Andet bevillings-/finansieringsnummer: São Paulo Research Foundation (FAPESP))

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

UBESLUTET

IPD-planbeskrivelse

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.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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