Liver Transplantation After ex Vivo Liver Perfusion

NCT05951231 | Not Yet Recruiting

• 1 other identifier: 598448
• Study Type: interventional
• Target: 22
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Keywords

Liver; Transplantation; Perfusion; Dual-end-ischemic Hypothermic Oxygenated Perfusion; Normothermic Machine Perfusion; Controlled Oxygenated Rewarming; Microdialysis

Outcome Measures

Primary Outcomes (1)

• 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 (303)

• Lactate level in microdialysate from liver tissue after normothermic machine perfusion - 2.5 hours

  2.5 hours

• Lactate level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours

  2 hours

• Pyruvate level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours

  2 hours

• Glycerol level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours

  2 hours

• Glucose level in microdialysate from liver tissue after Dual-end-ischemic Hypothermic Oxygenated Perfusion machine perfusion - 2 hours

  2 hours

Other Outcomes (8)

• Donor associated variables - age

  1 hour

• Donor associated variables - liver steatosis

  1 hour

• Donor associated variables - gender

  1 hour

Study Arms (2)

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

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)

Liver transplanted patient

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oslo University Hospital: lead
• South-Eastern Norway Regional Health Authority: collaborator

MeSH Terms

Conditions

Rejection, Psychology; Liver Neoplasms

Interventions

Liver Transplantation

Condition Hierarchy (Ancestors)

Social Behavior; Behavior; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Study Officials

• Søren E Pischke, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Søren E Pischke, MD, PhD

CONTACT

45486579; s.e.pischke@medisin.uio.no

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Single center, prospective, open, observational study

Study Record Dates

• First Submitted: April 4, 2023
• First Posted: July 18, 2023
• Study Start: February 1, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share