Hypothermic Oxygenated (HOPE) Versus Normothermic Machine Perfusion (NMP) in Human Liver Transplantation

NCT04644744 | Unknown DMC

• 1 other identifier: EA2/270/20
• Study Type: interventional
• Target: 213
• Locations: 1 country
• Sites: 4

Brief Summary

The common practice of conventional cold storage (CCS) organ preservation has changed little since the initial introduction of the original University of Wisconsin (UW) organ preservation solution in the late 1980s. CCS relies on hypothermia to decelerate metabolism and reduce oxygen demand in order to prolong the time of ischemia without rapid functional graft impairment, therefore merely delaying graft damage. While CCS only prolongs storage time and limits the damage sustained during the period of cold ischemia, ex-vivo machine perfusion (MP) appears to be capable of reversing some of these effects. Currently, two main paradigms prevail in the clinical approach to liver allograft MP: hypothermic oxygenated MP (HOPE) may be seen as a dynamic alternative of the traditional organ preservation based on hypothermia-induced deceleration of metabolism, which aims to combine the positive effects of hypothermia observed in classical cold storage (e.g. technical simplicity, relative safety, decreased metabolism) with the positive effects of dynamic preservation (e.g. controlled sheer stress mediated gene activation, removal of metabolites, transport of oxygen and ATP recharging). Normothermic perfusion (NMP) aims at re-equilibration of cellular metabolism by preserving the organ at physiological temperatures whilst ensuring sufficient oxygen and nutrient supply. In both approaches, the perpetual circulation and moderate shear-stress sustain endothelial functionality. While past and current clinical trials were designed to compare different MP approaches with CCS as the clinical standard, a direct comparison between different end-ischemic MP techniques (HOPE versus NMP) is still lacking. The purpose of this study is to test the effects of end-ischemic NMP versus end-ischemic HOPE technique in a multicentre prospective randomized controlled clinical trial (RCT) on ECD liver grafts in DBD liver-transplantation (HOPE-NMP). Two-hundred-thirteen (n = 213) human whole organ liver grafts will be submitted to either 4-24 hours of NMP (n = 85) or 2-3 hours of HOPE (n = 85) directly before implantation and going to be compared to a control-group of patients (n = 43) transplanted with static cold storage preserved ECD-allografts. Primary (surgical complications as assessed by the comprehensive complication index \[CCI\]) and secondary (among others laboratory values, graft- and patient survival, hospital costs, hospital stay) endpoints are going to be analysed.)

Conditions

Hepatocellular Injury; Liver Transplant Disorder

Keywords

ex-vivo machine Perfusion; Hypothermic oxygenated machine perfusion; Normothermic machine perfusion; Orthotopic liver transplantation; Extended criteria donation; Donation after brain death; HOPE; NMP

Outcome Measures

Primary Outcomes (1)

• Postoperative complications

  Comprehensive Complication Index (CCI) (assessed after the first 90-days postoperatively)

  After the first 90-days postoperatively

Secondary Outcomes (13)

• Peak alanine aminotransferase (ALT)

  During the first week postoperatively

• Peak aspartate aminotransferase (AST)

  During the first week postoperatively

• Early allograft dysfunction (EAD)

  During the first week postoperatively

• Primary non-function (PNF)

  During the first week postoperatively

• Biliary complications

  at 6 months postoperatively

Study Arms (3)

Hypothermic oxygenated perfusion (HOPE)

EXPERIMENTAL

Application of end-ischemic Hypothermic machine perfusion (HOPE) for a minimum of 2 hours (until hepatectomy)

Device: Hypothermic oxygenated perfusion (HOPE)

Normothermic machine perfusion (NMP)

EXPERIMENTAL

Application of end-ischemic normothermic machine perfusion (NMP) for a minimum of 4 hours (up to 24 hours)

Device: Normothermic machine perfusion (NMP)

Conventional cold storage (CCS)

ACTIVE COMPARATOR

Conventional cold storage

Device: Hypothermic oxygenated perfusion (HOPE); Device: Normothermic machine perfusion (NMP)

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)

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

Normothermic machine perfusion (NMP) DEVICE

End-ischemic NMP will be continued throughout the recipient hepatectomy and until the transplanting team is ready to implant the liver. The minimum protocol-stipulated NMP duration is 4 hours, the time needed for ATP repletion in animal studies. Total NMP preservation time will be according to the official recommendations of the manufacturer (4-24 hours) and at the discretion of the local transplant centre. The liver allograft will be disconnected from the OrganOx metra® device immediately prior to transplantation and flushed with three litres of HTK via the hepatic artery and the portal vein.

Conventional cold storage (CCS); Normothermic machine perfusion (NMP)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Patients 18 years or older
• Patients suffering from end stage-liver disease and/or malignant liver tumours
• Listed for OLT
• Receiving ECD-allografts

You may not qualify if:

• Recipients of split or 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 departments

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (4)

Charité Universitätsmedizin - Berlin, Campus Charité Mitte | Campus Virchow-Klinikum

Berlin, 13353, Germany

RECRUITING

University Hospital Bonn, Department of Surgery

Bonn, 53127, Germany

RECRUITING

Medizinische Hochschule Hannover (MHH), Department of Surgery and Transplantation

Hanover, 30625, Germany

NOT YET RECRUITING

University Hospital Heidelberg, Department of Surgery and Transplantation

Heidelberg, 69120, Germany

NOT YET RECRUITING

Related Links

• Study webpage

Study Officials

• Georg Lurje, M.D.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Georg Lurje, M.D.

CONTACT

+4930450652339; georg.lurje@charite.de

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: Consultant HPB- and Transplant Surgeon

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: November 13, 2020
• First Posted: November 25, 2020
• Study Start: January 14, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: July 22, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)