Hypothermic Machine Perfusion for Liver Graft Preservation

NCT07595627 | Not Yet Recruiting

• 2 other identifiers: 7.497.9912025/08106-0
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Liver Transplant; Liver Failure

Keywords

Hypothermic Machine Perfusion; Liver Transplantation; Ischemia-Reperfusion Injury; Ex Vivo Liver Perfusion; Extended Criteria Donors

Outcome Measures

Primary Outcomes (1)

• 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.

  Within 7 days after transplantation

Secondary Outcomes (8)

• Change in Liver Function Tests (AST, ALT, Total Bilirubin)

  At 7 days, 30 days, 6 months, and 1 year after transplantation

• Incidence of Acute Kidney Injury (AKI)

  Within 7 days and up to 30 days after transplantation

• Incidence of Post-Reperfusion Syndrome (PRS)

  During transplantation procedure

• Incidence of Post-Transplant Complications

  Up to 1 year after transplantation

• Graft Survival

  Up to 1 year after transplantation

Other Outcomes (4)

• Analysis of Perfusate Biomarkers

  During machine perfusion and immediately prior to transplantation

• Assessment of Mitochondrial Function Biomarkers (Flavin Mononucleotide, FMN)

  During machine perfusion period

• Assessment of Inflammatory Biomarkers

  During machine perfusion and within the first 7 days after transplantation

Study Arms (2)

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.

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.

Procedure: Static Cold Storage

Interventions

Hypothermic Machine Perfusion DEVICE

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.

Hypothermic Machine Perfusion

Static Cold Storage PROCEDURE

Liver graft preservation using conventional static cold storage under hypothermic conditions until transplantation.

Static Cold Storage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead
• XVIVO Perfusion: collaborator

Study Sites (1)

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)

São Paulo, São Paulo, 05403-000, Brazil

Location

Related Publications (2)

• 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.

  PMID: 32244972 BACKGROUND

• 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.

  PMID: 31249370 BACKGROUND

MeSH Terms

Conditions

Liver Failure; Reperfusion Injury

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wellington Andraus, MD, PhD

  Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)

  PRINCIPAL INVESTIGATOR

• Rubens Macedo Junior, MD, PhD

  Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)

  STUDY CHAIR

• Alexandre Santana, PhD

  Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)

  STUDY DIRECTOR

Central Study Contacts

Wellington Andraus, MD, PhD

CONTACT

+5511982118909; wellington@usp.br

Alexandre Santana, PhD

CONTACT

+5511931002779; alesantana@usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: May 19, 2026
• Study Start: May 7, 2026
• Primary Completion (Estimated): May 7, 2027
• Study Completion (Estimated): May 7, 2028
• Last Updated: May 19, 2026

Record last verified: 2026-05

Locations

BR (1)