Liver Transplantation After ex Vivo Liver Perfusion

NCT ID: NCT05951231

Last Updated: 2023-11-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-29
• Study Completion Date: 2029-02-28

Brief Summary

Today, it is difficult to predict liver function after transplantation and therefore livers where poor function is assumed (marginal livers) become discarded. The study aim is to increase the number of available donor livers, especially for liver cancer patients, by pre-treating and testing marginal ones (extended criteria donor (ECD) livers) liver on a liver perfusion machine. A liver perfusion machine can simulate liver transplantation and enables functional/quality testing before transplantation. The machine will hopefully also make marginal livers more functional by reducing ischemia- & reperfusion injury. A marginal donor liver is perfused ex situ with oxygenated blood from a blood donor on a machine. The liver can be tested here for function using internationally recognized criteria. At the same time, the investigators will carry out analyzes with microdialysis which can give a better picture of organ function and damage. Additionally, various samples of the liver and perfusate will be collected. Liver that achieves criteria for transplantation will be offered to the recipient.

Detailed Description

The study is a single-center, prospective, open-label cohort study designed to determine the efficacy of liver perfusion of marginal ECD livers on a perfusion machine before liver transplantation. Donor livers will be preserved with standard cooling followed by three perfusion modes (Dual hypothermic oxygenated machine perfusion (DHOPE) / Controlled oxygenated rewarming (COR) / Normothermic machine perfusion (NMP)), a method used internationally to pre-treating marginal livers before liver transplantation and which able testing of function and quality before a transplantation is performed. Only livers that fulfill international criteria (Groningen criteria) will be approved for Ltx. In this study microdialysis will be used to monitoring the liver during machine perfusion and up to 14 days in the postoperative course to monitor the function of the liver. The hypothesis is that microdialysis will provide a better prediction of liver function than the existing Groeningen criteria. The investigators expect that most included patients, who receive ECD livers perfused on a machine, will receive a postoperative well-functioning liver graft which entails a significant survival benefit. The study is designed as a cohort study because included patients have a very poor prognosis (median overall survival of approx. 6 months) and others treatment options are lacking. The primary objective is to establish definitive, objective criteria for pre-transplant liver function by defining a threshold value for microdialysis parameters (especially lactate) between donor livers that will restore function and those that will not during ex vivo machine perfusion in ECD livers, which are superior to established criteria (Groeningen and Viability testing and transplantation of marginal livers (VITTAL) criteria)). The primary endpoint is microdialysis lactate level between donor livers after 4 hours of normothermic machine perfusion in ECD livers.

The follow-up period is 12 months.

Conditions

Liver Transplant; Complications; Transplant; Failure, Liver; Transplant Dysfunction; Transplant; Complication, Rejection; Transplant; Liver Metastases; Liver Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Liver transplanted patient

Patients who are transplanted with an ECD liver after pretreatment with a liver perfusion machine

Group Type: ACTIVE_COMPARATOR

Liver transplantation

Intervention Type: PROCEDURE

Patients who receive an ECD liver after an ex-vivo liver perfusion where the liver has been tested for function and approved according to international functional criteria (Groeningen criteria)

Non-liver transplanted patient

Patients who are not offered a liver transplantation during the inclusion period

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Liver transplantation

Patients who receive an ECD liver after an ex-vivo liver perfusion where the liver has been tested for function and approved according to international functional criteria (Groeningen criteria)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Signed informed consent
• ≥ 18 years
• Indication for liver transplantation (one criteria must be met):
• Colorectal cancer patients who have received 1st and 2nd line chemotherapy where the treatment has been stopped due to progression or toxicity and the patient is not eligible for SECA-2 (Survival Following Liver Transplantation for Patients With Nonresectable Liver-only Colorectal Metastases) study.
• Hepatocellular carcinoma patients who are not suitable for standard liver transplantation, liver resection or local treatment (Transarterial Chemoembolisation or Selective internal radiotherapy). The patients must have progression or intolerance (toxicity) for immune checkpoint inhibitors or 1st line treatment.
• Cholangiocarcinoma patients who have progression or intolerance to first-line chemotherapy.
• Benign liver disease with urgent need for transplantation within months, but no regular graft is available.
• Life expectancy ≤ 6 months
• Willing, able and expected cooperation to attend follow-up examinations
• Patients who have a need for liver transplantation but cannot participate in other transplant studies or participation in another clinical trial with randomization to liver transplantation.

For malignant disease the following criteria must be met:

• Good performance status assessed at the discretion of the treating physician.
• ECOG (Eastern Cooperative Oncology Group) 0 or 1
• Satisfactory blood tests

• Hemoglobin >8 g/dl
• Neutrophiles >1.0 (after any Granulocyte colony-stimulating factor)
• Platelets >75
• Bilirubin <1.5 x upper normal level
• ASAT (Aspartate aminotransferase), ALAT (alanine aminotransferase) <5 x upper normal level
• Albumin above lower normal level.

Exclusion Criteria

• Already listed for ordinary Ltx with expectance of getting offered a regular liver graft within a reasonable time-frame.
• Patients included in the control arm of the SECA-3 study or the Excalibur studies except for the Ltx arm of the Excalibur I study.
• Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial.
• Any reason why, in the opinion of the investigator, the patient should not participate.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

South-Eastern Norway Regional Health Authority

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Søren Erik Pischke

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Søren E Pischke, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Central Contacts

Søren E Pischke, MD, PhD

Role: CONTACT

s.e.pischke@medisin.uio.no

45486579 ext. +47

Other Identifiers

598448

Identifier Type: -

Identifier Source: org_study_id