NCT03124641: HOPE-ECD-DBD

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

Completed NA Last updated 28 January 2021

What this trial tests

NA trial testing Hypothermic oxygenated perfusion (HOPE) in Hepatocellular Injury in 46 participants. Completed in 30 September 2020.

Timeline

17 January 2017

Primary endpoint
30 September 2020

30 September 2020

Quick facts

Lead sponsor	University Hospital, Aachen
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	46
Start date	17 January 2017
Primary completion	30 September 2020
Estimated completion	30 September 2020
Sites	4 locations across Germany, Czechia

Drugs / interventions tested

• Hypothermic oxygenated perfusion (HOPE)
• Conventional cold storage (CCS)

Conditions studied

• Hepatocellular Injury — all drugs for Hepatocellular Injury →
• Liver Transplant — all drugs for Liver Transplant →

Sponsor

University Hospital, Aachen

Who can join

Adults 18 to 75, any sex, with Hepatocellular Injury or Liver Transplant. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. From "Gut Feeling" to Objectivity: Machine Preservation of the Liver as a Tool to Assess Organ Viability.
   Watson CJE, Jochmans I. · · 2018 · cited 108× · PMID 29564205 · DOI 10.1007/s40472-018-0178-9
2. Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications.
   Czigany Z, Lurje I, Schmelzle M, Schöning W, et al · · 2020 · cited 79× · PMID 32244972 · DOI 10.3390/jcm9030846
3. 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).
   Czigany Z, Schöning W, Ulmer TF, Bednarsch J, et al · · 2017 · cited 56× · PMID 29018070 · DOI 10.1136/bmjopen-2017-017558
4. Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury-An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies.
   Nemeth N, Peto K, Magyar Z, Klarik Z, et al · · 2021 · cited 36× · PMID 33668478 · DOI 10.3390/ijms22041864
5. The dawn of liver perfusion machines.
   Detelich D, Markmann JF. · · 2018 · cited 35× · PMID 29324518 · DOI 10.1097/mot.0000000000000500
6. Improved outcomes after hypothermic oxygenated machine perfusion in liver transplantation-Long-term follow-up of a multicenter randomized controlled trial.
   Czigany Z, Uluk D, Pavicevic S, Lurje I, et al · · 2024 · cited 26× · PMID 38315126 · DOI 10.1097/hc9.0000000000000376
7. Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Liver Transplantation Mitigates Post-Reperfusion Syndrome and Perioperative Electrolyte Shifts.
   Horné F, Drefs M, Schirren MJ, Koch DT, et al · · 2022 · cited 18× · PMID 36555997 · DOI 10.3390/jcm11247381
8. Advances in Perfusion Systems for Solid Organ Preservation.
   Salehi S, Tran K, Grayson WL. · · 2018 · cited 18× · PMID 30258317