Clinical trial NCT04483102: RESTORE Declined Livers Study
Official title: A Prospective, Single-Center, Non-Randomized, Clinical Trial of Transplantation of Discarded Livers Using Normothermic Machine Perfusion (NMP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Liver Diseases
Surgery
Transplant; Failure, Liver
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Mid-America Transplant
name: OrganOx Ltd.
First posted: 2020-07-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To successfully transplant NMP-treated livers to patients that would otherwise have been discarded.
Primary purpose: TREATMENT

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).

Eligibility criteria: PRE-NMP DECLINED LIVER ELIGIBILITY:

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

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

Inclusion criteria:

* 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:

* 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.

Primary outcomes:
measure: Number of patients with no graft failure at 6 months
timeFrame: Up to 6 months
measure: Total number of patients who received NMP-treated liver transplantation
timeFrame: Up to 6 months
Secondary outcomes:
measure: Assess liver graft function and survival after transplantation
timeFrame: 3 months to 1 year
measure: Assess survival after transplantation
timeFrame: 3 months to 1 year
measure: To assess morbidity associated with receipt of NMP-treated liver
timeFrame: 3 months to 1 year
measure: Quality of Life Score Questionnaire
timeFrame: 6 months
measure: Estimate proportion of declined livers that can be used for transplantation following NMP
timeFrame: 12 months to 18 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Will Chapman, MD
role: PRINCIPAL_INVESTIGATOR
References: