RESTORE Declined Livers Study

NCT ID: NCT04483102

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-03
• Study Completion Date: 2025-12-31

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.

Detailed Description

This is a single center, prospective, non-randomized, clinical trial to assess the feasibility of successful transplantation of NMP-treated livers to patients. First, up to 71 marginal livers declined for transplantation will be treated with NMP using the OrganOx® metra device and tested for viability using previously defined criteria. NMP-treated viable livers will be subsequently transplanted to patients (n=5 in the 1st stage; additional 10 transplantation in the 2nd stage; additional 10 transplantation in the 3rd stage: total N=25). Patients will be closely followed for clinical outcomes of the transplantation during 6 months post-transplantation. The follow-up will also be extended up to 1 year post-transplantation. The trial will compare the results to those of three comparison groups - 1) matched patients who received liver transplantation at Washington University/Barnes Jewish Hospital; 2) matched patients who received DBD liver transplantation in the OPTN/UNOS database; and 3) matched patients who received DCD liver transplantation in the OPTN/UNOS database. Given that patient safety is the priority, the trial uses a multi-stage design in which the study stops earlier when NMP-treated liver transplantation is observed to be ineffective (see trial schema in Section 3.1).

Conditions

Liver Diseases; Surgery; Transplant; Failure, Liver

Study Design

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

Study Groups

Declined liver in Normothermic Machine Perfusion (NMP)

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.

Group Type: EXPERIMENTAL

Declined liver in Normothermic Machine Perfusion (NMP)

Intervention Type: 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.

Standard cold preservation of liver

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.

Group Type: ACTIVE_COMPARATOR

Standard cold preservation of liver

Intervention Type: 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.

Interventions

Declined liver in Normothermic Machine Perfusion (NMP)

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.

Intervention Type: DEVICE

Standard cold preservation of liver

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.

Intervention Type: PROCEDURE

Other Intervention Names

NMP-treated livers

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

Exclusion Criteria

• 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 is currently listed as a UNOS status 1A.
• Subject is requiring oxygen therapy via ventilator/respiratory support.
• Subject is planned to undergo simultaneous solid organ transplant.
• Subject is pregnant at the time of transplant.
• Subject MELD score 29 or higher
• Subject receives re-transplantation of liver.

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

Sponsors

Mid-America Transplant

OTHER

Sponsor Role: collaborator

OrganOx Ltd.

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Will Chapman, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36728302 (View on PubMed)

Other Identifiers

202007093

Identifier Type: -

Identifier Source: org_study_id