Cold Preservation vs. Machine Perfusion for Liver Transplants

Overseen By Heather Kuenz, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: HIV, Cirrhosis, Bridging fibrosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Immediate

25 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Declined liver in Normothermic Machine Perfusion (NMP) for liver transplants?

Research shows that using normothermic machine perfusion (NMP), which keeps the liver at body temperature, can be more effective than traditional cold storage methods. Studies suggest that NMP may reduce damage to the liver and improve outcomes after transplantation. ^{1 2 3 4 5}

Is normothermic machine perfusion (NMP) safe for liver transplants?

Normothermic machine perfusion (NMP) for liver transplants has been shown to be safe in clinical trials, with improved liver function compared to traditional cold storage methods. However, there are potential technical risks, and more extensive studies are needed to fully understand its safety profile. ^{1 5 6 7 8}

How does the treatment of declined liver in normothermic machine perfusion differ from other treatments for liver transplants?

Normothermic machine perfusion (NMP) is unique because it preserves donor livers at body temperature, allowing for better evaluation and potentially improved liver function compared to the traditional method of static cold storage (SCS), which keeps the liver at low temperatures. ^{1 2 5 7 9}

What is the purpose of this trial?

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.

Research Team

Will Chapman, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with end-stage liver disease who are on the UNOS waiting list for a primary liver transplant. They must be able to walk over 350 meters in six minutes or have mild/no frailty. Donors' livers, which were declined by other centers and meet specific criteria including weight and ischemia times, will be used.

Inclusion Criteria

My organ was not properly flushed during surgery.

I am considered not frail or mildly frail according to a recent test, or I can walk more than 350 meters in 6 minutes.

'Rapid Recovery' donors for liver procurement, meeting the above criteria

Exclusion Criteria

Subject MELD score 29 or higher

Donor serum bilirubin greater than or equal to 5 mg/dL

I am receiving a second liver transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Transplantation of NMP-treated livers to eligible patients

Immediate

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after transplantation

6 months

Regular visits (in-person)

Extended Follow-up

Long-term monitoring of liver graft function and patient survival

12 months

Treatment Details

Interventions

• Declined liver in Normothermic Machine Perfusion (NMP)
• Standard cold preservation of liver

Trial Overview The study compares outcomes of liver transplants using two preservation methods: standard cold storage versus Normothermic Machine Perfusion (NMP) with the OrganOx® metra device on previously discarded livers. The effectiveness of NMP-treated livers that pass viability tests will be evaluated over a year.

Participant Groups

Group I: Declined liver in Normothermic Machine Perfusion (NMP) Experimental Treatment 1 Intervention

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 II: Standard cold preservation of liver Active Control 1 Intervention

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.

Declined liver in Normothermic Machine Perfusion (NMP) is already approved in United States, European Union for the following indications:

Approved in United States as Normothermic Machine Perfusion for:

• Liver transplantation for end-stage liver disease

Approved in European Union as Normothermic Machine Perfusion for:

• Liver transplantation for end-stage liver disease

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

OrganOx Ltd.

Industry Sponsor

Trials

4

Recruited

630+

Mid-America Transplant

Collaborator

Trials

6

Recruited

1,700+

Findings from Research

In a study involving 383 donor livers from 15 US transplant centers, normothermic machine perfusion (NMP) did not significantly reduce early allograft dysfunction (EAD) compared to static cold storage (SCS), with rates of 20.6% for NMP and 23.7% for SCS.

However, NMP showed a notable benefit for higher-risk donor livers, particularly those from donors after circulatory death, where EAD rates were significantly lower (22.8% for NMP vs 44.6% for SCS), and it also reduced the incidence of postreperfusion syndrome (5.9% vs 14.6%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial. Chapman, WC., Barbas, AS., D'Alessandro, AM., et al.[2023]

Normothermic machine perfusion (NMP) significantly prolonged liver preservation time (21 hours) compared to static cold storage (SCS) (7 hours) without negatively impacting patient or graft survival rates after one year, which were similar between the two methods.

NMP was associated with a significantly lower incidence of ischaemic-type bile duct lesions (3% in NMP vs. 14% in SCS), suggesting that NMP may offer a safer preservation method for liver transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study. Fodor, M., Cardini, B., Peter, W., et al.[2022]

Hypothermic oxygenated machine perfusion (HOPE/D-HOPE) significantly improves graft and patient survival rates compared to static cold storage (SCS), with a hazard ratio of 0.40, indicating a 60% reduction in risk of graft failure.

HOPE also reduces the incidence of biliary complications compared to SCS, suggesting it is a safer option for preserving donor livers, while normothermic machine perfusion (NMP) did not show significant advantages over SCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Meta-Analysis and Systematic Review of Normothermic and Hypothermic Machine Perfusion in Liver Transplantation. Mugaanyi, J., Dai, L., Lu, C., et al.[2023]

Livers donated after circulatory death (DCD) that underwent in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) showed better early liver function and lower rates of acute kidney injury compared to those preserved with static cold storage (SCS).

NRP specifically demonstrated superior preservation of the biliary system, with no cases of clinically significant nonanastomotic strictures, while SCS had a 14% incidence of this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver Transplantation Outcomes From Controlled Circulatory Death Donors: SCS vs in situ NRP vs ex situ NMP. Gaurav, R., Butler, AJ., Kosmoliaptsis, V., et al.[2023]

Normothermic machine perfusion (NMP) for liver preservation shows promise in improving post-transplant outcomes and allows for longer preservation times, making it a potentially valuable option for increasing organ utilization.

Despite its benefits, NMP is more expensive and logistically challenging compared to traditional cold storage, which remains the standard method for preserving livers with good long-term survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold storage or normothermic perfusion for liver transplantation: probable application and indications. Ceresa, CDL., Nasralla, D., Knight, S., et al.[2022]

Normothermic machine perfusion (NMP) allows for safe preservation of livers for up to 38 hours before transplantation, with a successful transplantation rate of 92% among the 25 livers used, demonstrating its efficacy in managing marginal organs.

The implementation of NMP in a multidisciplinary setting resulted in no critical incidents or organ loss during 34 cases, indicating that this approach is both safe and feasible for routine clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Implementation of Prolonged Liver Preservation and Monitoring Through Normothermic Machine Perfusion in Liver Transplantation. Cardini, B., Oberhuber, R., Fodor, M., et al.[2021]

The preliminary North American trial of normothermic machine perfusion (NMP) for liver transplants showed that all transplanted livers functioned well, indicating the feasibility and safety of this method compared to standard static cold storage (SCS).

While graft survival at 30 days was similar between NMP and SCS groups, the NMP group experienced longer intensive care and hospital stays, suggesting potential technical risks that need to be addressed in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Single-Center Canadian Experience of Human Normothermic Ex Vivo Liver Perfusion: Results of a Clinical Trial. Bral, M., Gala-Lopez, B., Bigam, D., et al.[2023]

Normothermic machine perfusion (NMP) has shown promising safety and efficacy in preserving donor livers for transplantation, with a low rate of post-transplant complications such as primary non-function (PNF) and early allograft dysfunction (EAD) compared to static cold storage (SCS).

In a review of five prospective clinical trials involving 460 donor livers, NMP provided a more favorable environment for organ preservation and viability assessment, although further studies are needed to confirm these findings and explore additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Normothermic Perfusion in Liver Transplantation (TRaNsIT Study): A Systematic Review of Preliminary Studies. Jayant, K., Reccia, I., Virdis, F., et al.[2023]

In a pilot study involving 7 liver grafts from donors after cardiac death (DCD) and brain death (DBD), hypothermic oxygenated machine perfusion (HOPE) demonstrated safety and efficacy, with a 100% patient and graft survival rate after transplantation.

The study highlighted that steatosis was a significant risk factor for kidney injury post-transplant, emphasizing the importance of careful evaluation of graft quality, especially in the context of extended-criteria donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Experience With Hypothermic Oxygenated Machine Perfusion in an Italian Liver Transplant Center. Dondossola, D., Lonati, C., Zanella, A., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Meta-Analysis and Systematic Review of Normothermic and Hypothermic Machine Perfusion in Liver Transplantation. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Liver Transplantation Outcomes From Controlled Circulatory Death Donors: SCS vs in situ NRP vs ex situ NMP. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Cold storage or normothermic perfusion for liver transplantation: probable application and indications. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical Implementation of Prolonged Liver Preservation and Monitoring Through Normothermic Machine Perfusion in Liver Transplantation. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Preliminary Single-Center Canadian Experience of Human Normothermic Ex Vivo Liver Perfusion: Results of a Clinical Trial. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

The Role of Normothermic Perfusion in Liver Transplantation (TRaNsIT Study): A Systematic Review of Preliminary Studies. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Preliminary Experience With Hypothermic Oxygenated Machine Perfusion in an Italian Liver Transplant Center. [2019]