RESTORE Declined Livers Study

NCT04483102 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 202007093
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, non-randomized, clinical trial of discarded liver transplants that have received normothermic machine perfusion (NMP), compared with standard cold preservation liver transplants. The discarded livers rejected by all other centers and meeting pre-NMP eligibility criteria will receive NMP using the OrganOx® metra device. The NMP-treated liver that meets the viability criteria will be transplanted to patients who are eligible and consented to the study. Liver transplant outcomes will be ascertained during 12 months post-transplantation. The results of the trial will be compared with those of contemporary comparison groups of patients who received the standard criteria donor liver transplantation.

Conditions

Liver Diseases; Surgery; Transplant; Failure, Liver

Outcome Measures

Primary Outcomes (2)

• Number of patients with no graft failure at 6 months

  6-month graft and patient survival as an indicator of liver function after NMP- treated liver transplantation. 6-month patient survival rate will be estimated as the number of patients who survive by 6 months post-transplantation with NMP-treated livers This is a nationally accepted outcome routinely assessed in organ transplantation programs. 6-month graft survival rate = (Number of patients with no graft failure at 6-month post transplantation)/(Total number patients who received transplantation with NMP-treated liver) 6-month graft and patient survival rates will be compared to those in each comparison group using Fisher's Exact test. Kaplan-Meier survival curve will be examined as well.

  Up to 6 months

• Total number of patients who received NMP-treated liver transplantation

  6-month patient survival rate will be estimated as the number of patients who survive by 6 months post-transplantation with NMP-treated livers divided by the total number of patients who received NMP-treated liver transplantation. 6-month patient survival rate = (Number of patients who survive by 6-month post transplantation)/(Total number patients who received transplantation with NMP-treated liver) 6-month graft and patient survival rates will be compared to those in each comparison group using Fisher's Exact test. Kaplan-Meier survival curve will be examined as well.

  Up to 6 months

Secondary Outcomes (5)

• Assess liver graft function and survival after transplantation

  3 months to 1 year

• Assess survival after transplantation

  3 months to 1 year

• To assess morbidity associated with receipt of NMP-treated liver

  3 months to 1 year

• Quality of Life Score Questionnaire

  6 months

• Estimate proportion of declined livers that can be used for transplantation following NMP

  12 months to 18 months

Study Arms (2)

Declined liver in Normothermic Machine Perfusion (NMP)

EXPERIMENTAL

The discarded livers rejected by all other centers and meeting pre-NMP eligibility criteria will receive NMP using the OrganOx® metra device. The NMP-treated liver that meets the viability criteria will be transplanted to patients who are eligible and consented to the study. NMP of the donated declined liver utilizing the OrganOx® metra device. NMP involves (warm) machine perfusion with oxygenated blood at normal body temperature. During NMP, the device also allows for ongoing assessment of donor liver function and further viability assessment to help determine suitability of the organ for transplant.

Device: Declined liver in Normothermic Machine Perfusion (NMP)

Standard cold preservation of liver

ACTIVE COMPARATOR

This group will receive liver transplant using the standard method of preservation. There will be 3 comparison groups: one local comparison group and two comparison groups from the national UNOS data.

Procedure: Standard cold preservation of liver

Interventions

Declined liver in Normothermic Machine Perfusion (NMP) DEVICE

The discarded livers rejected by all other centers and meeting pre-NMP eligibility criteria will receive NMP using the OrganOx® metra device. The NMP-treated liver that meets the viability criteria will be transplanted to patients who are eligible and consented to the study.

Also known as: NMP-treated livers

Declined liver in Normothermic Machine Perfusion (NMP)

Standard cold preservation of liver PROCEDURE

The study will have three comparison groups - one local comparison group and two comparison groups from the national UNOS data. Comparison group 1 will be patients who received a standard liver transplantation and follow-up care at the Washington University/ Barnes Jewish Hospital (n=50). Patients will be matched by a 5-year age category, sex, MELD score, donor liver graft type (e.g., DCD, DBD), donor age (5-year category), and donor sex. Washington University/ Barnes Jewish Hospital maintains a liver transplantation database that prospectively collects pre- and post-transplantation patient data. Comparison group 2 will be patients who received DBD liver transplantation in the OPTN/UNOS database (n=100). Patients will be matched by age, sex, MELD score, donor age, and donor sex. Comparison group 3 will be patients who received DCD liver transplantation in the OPTN/UNOS database (n=100). Patients will be matched by age, sex, MELD score, donor age, and donor sex.

Standard cold preservation of liver

Eligibility Criteria

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

You may qualify if:

• DCD donor aged 6 years or greater and liver weight between 1 kg and 3.4 kg, with functional warm ischemic time (defined as the period between the systolic blood pressure less than 60 mmHg to the time of commencing donor aortic perfusion) in DCD donors less than 40 minutes
• DCD asystolic warm ischemia time (from heartbeat stopping to initiation of cold flush) less than 15 minutes
• DBD donor aged 6 years or greater and liver weight between 1 kg and 3.4 kg, with less than 8 hours cold ischemia time and DCD livers with less than 7 hours cold ischemia time (defined as the interim from initiation of donor in vivo cold organ preservation to removal of the liver graft from cold storage)
• 'Rapid Recovery' donors for liver procurement, meeting the above criteria
• Suboptimal in situ flush

You may not qualify if:

• DBD or DCD donor less than 6 years old
• DCD grafts with donor functional warm ischemic time (defined as the period between the systolic blood pressure less than 60 mmHg to the time of commencing donor aortic perfusion) greater than or equal to 40 minutes
• DCD asystolic warm ischemia time (from heartbeat stopping to initiation of cold flush) greater than or equal to 15 minutes
• DBD livers with cold ischemia time greater than or equal to 8 hours and DCD livers with greater than or equal to 7 hours cold ischemia time
• Donor serum bilirubin greater than or equal to 5 mg/dL
• Liver weight less than 1 kg or greater than or equal to 3.5 kg
• Grafts from patients with HIV infection
• Cirrhotic livers
• Livers with bridging fibrosis
• LIVER TRANSPLANTATION - HUMAN
• Subject must be greater than or equal to 18 years of age.
• Subject with end-stage liver disease who is actively listed for primary liver transplantation on the UNOS waiting list
• Subject, or a legally authorized representative, has given informed consent to participate in the study
• Subject has a frailty classification of "Mild frailty/No frailty (Robust)", based on the Liver Frailty Index (LFI), which has been assessed within 6 months prior to liver transplant OR Subject is able to perform \>350 m on a 6 minute walk test (6MWT) within 6 months prior to liver transplant.
• In all cases, the "most recent" (and within 6 months prior to transplant) measurement of LFI or 6MWT will be used to determine eligibility.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Mid-America Transplant: collaborator
• OrganOx Ltd.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Olumba FC, Zhou F, Park Y, Chapman WC; RESTORE Investigators Group. Normothermic Machine Perfusion for Declined Livers: A Strategy to Rescue Marginal Livers for Transplantation. J Am Coll Surg. 2023 Apr 1;236(4):614-625. doi: 10.1097/XCS.0000000000000555. Epub 2023 Jan 11.

  PMID: 36728302 DERIVED

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Will Chapman, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: To successfully transplant NMP-treated livers to patients that would otherwise have been discarded.

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 23, 2020
• Study Start: December 3, 2020
• Primary Completion: May 14, 2025
• Study Completion: December 31, 2025
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)