HOPE for Human Extended Criteria and Donation After Brain Death Donor (ECD-DBD) Liver Allografts

NCT03124641 | Completed DMC

• 1 other identifier: EK 049/17
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study is to test the effects of hypothermic oxygenated machine perfusion (HOPE) in a phase-II prospective multicenter randomized clinical trial (RCT) on extended criteria donor allografts (ECD) in donation after brain death (DBD) orthotropic liver-transplantation (OLT) (HOPE-ECD-DBD). Human whole organ liver grafts will be submitted to 1-2 hours of HOPE via the portal vein directly before implantation and going to be compared to a control-group of patients transplanted after conventional cold storage (CCS). Primary (early graft injury) and secondary (e.g. postoperative complications, hospital stay, survival) objectives are going to be analysed in a 12 month follow up. Ischemia-reperfusion (I/R) injury and inflammation will be assessed using liver tissue, serum and bile samples as well as machine perfusion perfusate. To improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with higher incidences of primary graft non-function (PNF) and/or delayed graft function (DGF). As such, several strategies have been developed aiming at "reconditioning" poor quality ECD grafts. HOPE has been tested intensively in pre-clinical animal experiments. Although, its known that HOPE can exert its reconditioning effect via cellular and mitochondrial pathways in the endothelial and parenchymal cells, there is still scarce evidence available on the exact subcellular mechanism of HOPE induced organ protection in the clinical scenario of liver transplantation. In donation after cardiac death (DCD) OLT, the positive effects of HOPE have been shown to reduce the incidence of biliary complications, mitochondrial damage and improve the overall cellular energy-status. In the HOPE setting, organ perfusion is performed in the transplant center shortly before the actual implantation with oxygenated perfusate using an extra corporal organ perfusion system. The first clinical study with this promising technique was recently reported in a Swiss cohort of patients who received DCD allografts. In organ donation after brain death (DBD), the only legally accepted approach for organ donation in most countries, HOPE and its effect on early graft injury and postoperative complications remains to be elucidated.

Conditions

Hepatocellular Injury; Liver Transplant

Keywords

Hypothermic oxygenated machine perfusion; Orthotopic liver transplantation; Extended criteria donation; Donation after brain death; HOPE

Outcome Measures

Primary Outcomes (1)

• Early graft injury

  Peak serum alanine aminotransferase-ALT

  During the first week postoperatively (absolute and relative delta)

Secondary Outcomes (8)

• Postoperative complications

  Subjects will be followed for one year postoperatively

• Cumulative postoperative complications

  Subjects will be followed for one year postoperatively

• Early allograft dysfunction (EAD)

  During the first week postoperatively

• Duration of intensive care stay

  Subjects will be followed for one year postoperatively

• Duration of hospital stay

  Subjects will be followed for one year postoperatively

Study Arms (2)

Hypothermic oxygenated perfusion (HOPE)

EXPERIMENTAL

Application of Hypothermic machine perfusion (HOPE) for 1-2 hours

Device: Hypothermic oxygenated perfusion (HOPE)

Conventional cold storage (CCS)

ACTIVE COMPARATOR

Conventional cold storage

Procedure: Conventional cold storage (CCS)

Interventions

Hypothermic oxygenated perfusion (HOPE) DEVICE

HOPE for 1 hour via the portal vein in a recirculating and pressure controlled system (2-3 mm Hg), 0.1 ml/g liver/min, perfusion volume 3-4 L, Belzer (UW) machine perfusion solution, perfusate temperature 10 °C, perfusate oxygenation pO2 of 60-80 kPa

Also known as: Hypothermic machine perfusion (HMP)

Hypothermic oxygenated perfusion (HOPE)

Conventional cold storage (CCS) PROCEDURE

Conventional static cold storage (CCS) on temperature 4-6 °C from organ procurement

Also known as: CCS

Conventional cold storage (CCS)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with signed informed consent, suffering from end stage-liver disease and/or malignant liver tumors listed for liver transplantation and receiving ECD organs.
• ECD Criteria are defined as:
• Donors 65 years of age and older
• Intensive therapy of the donor was required before donation for at least 7 days, --Obesity of the donor with a Body Mass Index \> 30
• Fatty liver (with histology) \> 40 %
• Serum-Sodium \> 165 mmol/l
• Serum AST or ALT \> 3 x normal, Serum-Bilirubin \> 2 mg/dl)

You may not qualify if:

• Recipients of split of living donor liver transplants
• Previous liver transplantation
• Combined transplantations (liver-kidney, liver-lung, etc.)
• Participation in other liver related trials
• The subject is unwilling or unable to follow the procedures outlined in the protocol
• The subject is mentally or legally incapacitated
• Patient is not able to understand the procedures due to language barriers
• Family members of the investigators or employees of the participating department

Sponsors & Collaborators

• University Hospital, Aachen: lead

Study Sites (4)

Department of Transplantation Surgery, Institute for Clinical and Experimental Medicine

Prague, Czechia

Location

Department of Surgery and Transplantation, University Hospital RWTH Aachen

Aachen, 52074, Germany

Location

Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Germany

Berlin, 13353, Germany

Location

Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich

Munich, 81377, Germany

Location

Related Publications (3)

• Czigany Z, Schoning W, Ulmer TF, Bednarsch J, Amygdalos I, Cramer T, Rogiers X, Popescu I, Botea F, Fronek J, Kroy D, Koch A, Tacke F, Trautwein C, Tolba RH, Hein M, Koek GH, Dejong CHC, Neumann UP, Lurje G. Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD). BMJ Open. 2017 Oct 10;7(10):e017558. doi: 10.1136/bmjopen-2017-017558.

  PMID: 29018070 BACKGROUND

• Schliephake F, Lurje I, Uluk D, Eden J, Czigany Z, Pein J, Husen P, Engelmann C, Michalski C, Kohlhepp M, Strnad P, Dutkowski P, Tacke F, Neumann UP, Meierhofer D, Lurje G. Effects of hypothermic oxygenated machine perfusion on bile composition after liver transplantation - Findings from a randomized controlled trial. JHEP Rep. 2025 Oct 17;8(2):101647. doi: 10.1016/j.jhepr.2025.101647. eCollection 2026 Feb.

  PMID: 41551407 DERIVED

• Czigany Z, Pratschke J, Fronek J, Guba M, Schoning W, Raptis DA, Andrassy J, Kramer M, Strnad P, Tolba RH, Liu W, Keller T, Miller H, Pavicevic S, Uluk D, Kocik M, Lurje I, Trautwein C, Mehrabi A, Popescu I, Vondran FWR, Ju C, Tacke F, Neumann UP, Lurje G. Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD). Ann Surg. 2021 Nov 1;274(5):705-712. doi: 10.1097/SLA.0000000000005110.

  PMID: 34334635 DERIVED

Related Links

• HOPE ECD-DBD webpage

Study Officials

• Georg Lurje, M.D.

  RWTH Aachen University I Charité-Universitätsmedizin Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Transplant Surgeon

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: March 20, 2017
• First Posted: April 24, 2017
• Study Start: January 17, 2017
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: January 28, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); CZ (1)