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

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

Interventions

DEVICE

Hypothermic oxygenated perfusion (HOPE)

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

PROCEDURE

Conventional cold storage (CCS)

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

Sponsors & Collaborators

• University Hospital, Aachen

  lead OTHER

Principal Investigators

• Georg Lurje, M.D. · RWTH Aachen University I Charité-Universitätsmedizin Berlin

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-01-17

Primary Completion

2020-09-30

Completion

2020-09-30

Countries

• Czechia
• Germany

Study Locations