Liver Transplantation After ex Vivo Liver Perfusion | NCT05951231

NCT05951231

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
South-Eastern Norway Regional Health Authority	OTHER

Description Module

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Liver transplanted patient	Active Comparator	Patients who are transplanted with an ECD liver after pretreatment with a liver perfusion machine	Procedure: Liver transplantation
Non-liver transplanted patient	No Intervention	Patients who are not offered a liver transplantation during the inclusion period

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Liver transplantation	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)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Lactate level in microdialysate from hilar plate after normothermic machine perfusion - 4 hours	Lactate level in microdialysate from hilar plate after normothermic machine perfusion in extended criteria donors livers.	4 hours

Secondary Outcomes

Measure	Description	Time Frame
Lactate level in microdialysate from liver tissue after normothermic machine perfusion - 2.5 hours	Microdialysis lactate level in donor liver tissue after 2.5 hours of normothermic machine perfusion in extended criteria donors livers.	2.5 hours
Lactate level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours

Measure	Description	Time Frame
Donor associated variables - age	Age of the donor (years)	1 hour
Donor associated variables - liver steatosis	Assessment of liver steatosis (%)

Eligibility Module

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.

ID	Term
D012059	Rejection, Psychology
D008113	Liver Neoplasms

ID	Term
D012919	Social Behavior
D001519	Behavior
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site

ID	Term
D016378	Tissue Transplantation
D064987	Cell- and Tissue-Based Therapy
D001691	Biological Therapy
D013812	Therapeutics