Liver TransplantHOPE-LiverNCT07595627
Hypothermic Machine Perfusion for Liver Graft Preservation
A study testing Hypothermic Machine Perfusion and Static Cold Storage in people with Liver Transplant and Liver Failure, run by University of Sao Paulo General Hospital at 1 site in Brazil.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplant, Liver Failure
- What is being tested?
- Hypothermic Machine Perfusion and Static Cold Storage
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteBrazil
- Study dates
- 7 May 2026to 7 May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
São Paulo, São Paulo, 05403-000
Wellington Andraus, MD, PhD, +5511982118909, wellington@usp.br
Alexandre Santana, PhD, +5511931002779, alesantana@usp.br
About this study
Official title: 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:
Read more
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.
Read the detailed description
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.
- Conditions
- Liver Transplant, Liver Failure
- Being tested
- Hypothermic Machine Perfusion, Static Cold Storage
- Keywords
- Hypothermic Machine Perfusion, Liver Transplantation, Ischemia-Reperfusion Injury, Ex Vivo Liver Perfusion, Extended Criteria Donors
- Medical subject headings
- Liver Failure, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypothermic Machine PerfusionDevice
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.
Static Cold StorageProcedure or surgery
Liver graft preservation using conventional static cold storage under hypothermic conditions until transplantation.
| Study group | Role | What they receive |
|---|---|---|
| Hypothermic Machine Perfusion | Experimental | 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. Receives: Device: Hypothermic Machine Perfusion |
| Static Cold Storage | Active comparator | 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. Receives: Procedure: Static Cold Storage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Early Allograft Dysfunction (EAD)
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.
Measured: Within 7 days after transplantation
Secondary outcomes (8)
Change in Liver Function Tests (AST, ALT, Total Bilirubin)
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.
Measured: At 7 days, 30 days, 6 months, and 1 year after transplantation
Incidence of Acute Kidney Injury (AKI)
Occurrence of acute kidney injury following liver transplantation, defined based on changes in serum creatinine levels according to established clinical criteria.
Measured: Within 7 days and up to 30 days after transplantation
Incidence of Post-Reperfusion Syndrome (PRS)
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.
Measured: During transplantation procedure
Incidence of Post-Transplant Complications
Occurrence of post-transplant complications, including biliary complications, vascular complications, infections, and acute rejection, assessed according to standard clinical definitions and severity grading systems.
Measured: Up to 1 year after transplantation
Graft Survival
Survival of the transplanted liver graft without the need for retransplantation
Measured: Up to 1 year after transplantation
Patient Survival
Survival of the transplant recipient following liver transplantation.
Measured: Up to 1 year after transplantation
Length of Intensive Care Unit Stay
Duration of stay in the intensive care unit following liver transplantation.
Measured: From liver transplantation until intensive care unit discharge, up to 30 days
Length of Hospital Stay
Duration of hospital stay following liver transplantation.
Measured: From liver transplantation until hospital discharge, up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2026
- Study start7 May 2026 (estimated)
- Primary completion7 May 2027 (estimated)
- Study completion7 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver TransplantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, single-center, two-arm, parallel-group randomized controlled trial comparing two liver graft preservation strategies in adult liver transplantation. Participants will be allocated in a 1:1 ratio to receive a graft preserved either by hypothermic machine perfusion or by conventional static cold storage. Randomization will be performed using a computer-generated sequence, with each participant assigned to a single intervention arm and no crossover between groups. The intervention is applied at the graft level prior to transplantation. All transplant procedures and perioperative management will be conducted according to standard institutional protocols.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- XVIVO Perfusion
- Responsible party
- Sponsor
- Investigators
- Wellington Andraus, MD, PhD, Principal investigator, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)Rubens Macedo Junior, MD, PhD, Study chair, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)Alexandre Santana, PhD, Study director, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07595627
- Sponsor's protocol ID
- 7.497.991
- Other IDs
- 2025/08106-0, 2025
- Acronym
- HOPE-Liver
- Status last verified
- May 2026
- First submitted
- 6 May 2026
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Publications
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.
PubMed 32244972Patrono 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.
PubMed 31249370
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective and Randomized Clinical Study of the Effect of Hypothermic Machine Perfusion on Liver Graft Preservation
- ClinicalTrials.gov ID
- NCT07595627
- Acronym / sponsor ID
- HOPE-Liver / 7.497.991
- Conditions
- Liver Transplant, Liver Failure
- Keywords
- Hypothermic Machine Perfusion, Liver Transplantation, Ischemia-Reperfusion Injury, Ex Vivo Liver Perfusion, Extended Criteria Donors
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Collaborators
- XVIVO Perfusion
- Study start
- 7 May 2026 (estimated)
- Primary completion
- 7 May 2027 (estimated)
- Study completion
- 7 May 2028 (estimated)
- First posted
- 19 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective, single-center, two-arm, parallel-group randomized controlled trial comparing two liver graft preservation strategies in adult liver transplantation. Participants will be allocated in a 1:1 ratio to receive a graft preserved either by hypothermic machine perfusion or by conventional static cold storage. Randomization will be performed using a computer-generated sequence, with each participant assigned to a single intervention arm and no crossover between groups. The intervention is applied at the graft level prior to transplantation. All transplant procedures and perioperative management will be conducted according to standard institutional protocols.
| Arm | Type | Receives |
|---|---|---|
| Hypothermic Machine Perfusion | Experimental | Device: Hypothermic Machine PerfusionLiver 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. |
| Static Cold Storage | Active comparator | Procedure: Static Cold StorageLiver 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypothermic Machine PerfusionHypothermic 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. | Device | Hypothermic Machine Perfusion |
| Static Cold StorageLiver graft preservation using conventional static cold storage under hypothermic conditions until transplantation. | Procedure or surgery | Static Cold Storage |
Primary outcome
Incidence of Early Allograft Dysfunction (EAD)
Time frame: 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.
8 secondary outcomes
Change in Liver Function Tests (AST, ALT, Total Bilirubin)
Time frame: At 7 days, 30 days, 6 months, and 1 year after transplantation
Incidence of Acute Kidney Injury (AKI)
Time frame: Within 7 days and up to 30 days after transplantation
Incidence of Post-Reperfusion Syndrome (PRS)
Time frame: During transplantation procedure
Incidence of Post-Transplant Complications
Time frame: Up to 1 year after transplantation
Graft Survival
Time frame: Up to 1 year after transplantation
Patient Survival
Time frame: Up to 1 year after transplantation
Length of Intensive Care Unit Stay
Time frame: From liver transplantation until intensive care unit discharge, up to 30 days
Length of Hospital Stay
Time frame: From liver transplantation until hospital discharge, up to 30 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Background: PubMed 32244972Czigany 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.
- Background: PubMed 31249370Patrono 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.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wellington Andraus, MD, PhD principal investigator
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
Rubens Macedo Junior, MD, PhD study chair
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
Alexandre Santana, PhD study director
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypothermic Machine Perfusion and Static Cold Storage in people with Liver Transplant and Liver Failure, run by University of Sao Paulo General Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wellington Andraus, MD, PhD (+5511982118909, wellington@usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Early Allograft Dysfunction (EAD) (time frame: Within 7 days after transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07595627, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.