Normothermic Machine Perfusion for Liver Transplant

Overseen By Heidi Yeh, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Cardiac, Pulmonary, Prior liver transplant, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to enhance the health of certain donor livers for transplant. It employs Normothermic Machine Perfusion (NMP) to improve livers with moderate fat buildup (30-60% macrosteatosis), aiming for safer transplants. The trial seeks to determine if this approach can increase the number of livers available for patients in need of a transplant. Suitable candidates have liver disease, are listed for a transplant at Massachusetts General Hospital, and possess a MELD-Na score of 15 to 25, indicating liver disease severity. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could expand the availability of healthy donor livers.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that Normothermic Machine Perfusion is safe for liver transplantation?

Research has shown that Normothermic Machine Perfusion (NMP) is generally safe for liver transplants. One study demonstrated that using NMP reduced liver damage by half, even in challenging situations. Another study found that NMP is safe and effective for long-term use. These studies suggest that NMP is well-tolerated, with a low risk of serious complications related to liver transplants shortly after surgery. Overall, the evidence indicates that NMP is a promising and safe option for improving liver transplant outcomes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Normothermic Machine Perfusion (NMP) for liver transplants because it offers a novel approach to improving the viability of steatotic livers, which are often too fatty to be used in transplants. Unlike traditional cold storage methods, NMP keeps the liver at body temperature and pumps it with oxygen and nutrients, which can rejuvenate the organ and make it suitable for transplant. This technique could expand the donor pool by making more livers usable, potentially reducing wait times for patients. Additionally, NMP allows real-time assessment of liver function before transplantation, which can help improve outcomes for recipients.

What evidence suggests that Normothermic Machine Perfusion is effective for liver transplantation?

Research has shown that Normothermic Machine Perfusion (NMP), which participants in this trial may receive, can improve liver transplant success. Studies have found that NMP leads to better survival rates for both patients and transplanted livers. It also enables doctors to evaluate and use more livers that might otherwise be discarded. NMP proves especially useful for treating livers from donors who died from circulatory issues, increasing the likelihood of successful function. This advancement means more people could receive the liver transplants they need. Overall, NMP offers a promising method to increase liver availability and enhance transplant success. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 who are on the liver transplant list at MGH with a MELD-Na score of 25 or less and can give consent. It's not suitable for those outside this age range, with higher MELD-Na scores, or unable to consent.

Inclusion Criteria

Listed for liver transplantation at MGH

Calculated MELD-Na score <= 25

Able to consent

Exclusion Criteria

My liver is functioning well enough (MELD score below 15) and I don't have symptoms from liver disease.

I have a history of heart or lung disease.

I have had a liver transplant in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Donor livers with 30-60% macrosteatosis are placed on Normothermic Machine Perfusion (NMP) and transplanted if they meet viability criteria

Immediate

Follow-up

Participants are monitored for safety and effectiveness after transplantation, with assessments at 3, 6, and 12 months post-transplant

12 months

Extension

Potential for trial extension to include severely steatotic livers based on study results

What Are the Treatments Tested in This Trial?

Interventions

• Normothermic Machine Perfusion

Trial Overview The study tests if Normothermic Machine Perfusion (NMP) can make moderately fatty livers safe for transplant by keeping them functioning at normal body temperature after donation and before transplantation.

How Is the Trial Designed?

Group I: Liver Transplantation with Steatotic Liver Experimental Treatment 1 Intervention

Graft will be selected if 30-60% macrosteatosis and transplanted into liver transplant recipient with MELD of 15-25.

Normothermic Machine Perfusion is already approved in United States, European Union for the following indications:

Approved in United States as Normothermic Machine Perfusion for:

• Liver transplantation
• Expansion of donor organ pool for liver transplantation

Approved in European Union as Normothermic Machine Perfusion for:

• Liver transplantation
• Assessment and preservation of donor livers

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Normothermic machine perfusion of the liver (NMP-L) has been shown to be safe and feasible, allowing for liver preservation for up to 24 hours, which is a significant improvement over traditional cold storage methods.

NMP-L enables the assessment of liver function during preservation, which can help identify viable organs, particularly high-risk livers, potentially increasing the number of donor organs available for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normothermic ex-situ liver preservation: the new gold standard. Laing, RW., Mergental, H., Mirza, DF.[2018]

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]

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]

Normothermic machine perfusion (NMP) significantly reduces the discard rate of donor livers, with only 3.5% discarded compared to 13.3% for standard cold-static preservation, even though NMP livers often come from older and higher-risk donors.

Despite using livers from donors considered marginally suitable, NMP maintains excellent graft and patient survival rates, suggesting that its broader application could greatly increase the availability of transplantable livers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Making Every Liver Count: Increased Transplant Yield of Donor Livers Through Normothermic Machine Perfusion. MacConmara, M., Hanish, SI., Hwang, CS., et al.[2021]

Normothermic machine perfusion (NMP) at 38.5°C significantly improved the preservation of donation after cardiac death (DCD) liver grafts compared to subnormothermic machine perfusion (SNMP) at 21°C and cold storage (CS) at 4°C, as evidenced by lower levels of hepatocellular enzymes and higher bile production in the NMP group.

In a study involving 15 porcine livers preserved for 10 hours, NMP demonstrated superior hepatocellular integrity and biliary function, indicating its potential as a more effective method for preserving marginal liver grafts for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Temperature on Porcine Liver Machine Perfusion From Donors After Cardiac Death. Nassar, A., Liu, Q., Farias, K., et al.[2017]

Normothermic machine perfusion (NMP) allows for the successful transplantation of more marginal livers, as evidenced by a higher Donor Risk Index and increased use of donation after cardiac death, while still achieving similar one-year graft survival rates compared to traditional static cold storage (SCS).

NMP not only benefits patients by facilitating transplants for those with lower MELD scores who have been waitlisted longer, but it also shifts the timing of surgeries from nighttime to daytime, potentially improving the working conditions and quality of life for transplant teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From Patients to Providers: Assessing the Impact of Normothermic Machine Perfusion on Liver Transplant Practices in the US. Wang, BK., Shubin, AD., Harvey, JA., et al.[2023]

Normothermic machine perfusion (NMP) shows promise in improving liver preservation and reconditioning high-risk grafts, with early clinical results indicating beneficial effects.

NMP not only helps assess graft viability but also has the potential to extend preservation periods and allow for targeted interventions, although further validation through large randomized control trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normothermic liver preservation, current status and future directions. Detelich, D., Markmann, JF.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34985503/

The OCS Liver PROTECT Randomized Clinical Trial Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

2. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2787486

Impact of Portable Normothermic Blood-Based Machine ... In this study, portable normothermic oxygenated machine perfusion of donor liver grafts resulted in improved outcomes after liver transplant and in more livers ...

3. journals.lww.com journals.lww.com/lt/fulltext/2025/06000/transforming_the_logistics_of_liver.9.aspx

Transforming the logistics of liver transplantation with... Normothermic machine perfusion (NMP) has emerged as an alternative organ preservation strategy to traditional static cold storage (SCS).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11230788/

Normothermic Machine Perfusion Is Associated ... Use of NMP for LT from DCD donors was associated with improved posttransplant patient and graft survival.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666967623000399

24-hour normothermic machine perfusion of discarded ... Normothermic machine perfusion (NMP) has the potential to extend viability and allow liver function evaluation in discarded organs. The main aim of the study ...

6. aasld.org aasld.org/liver-fellow-network/core-series/why-series/why-machine-perfusion-has-potential-change-liver

Why machine perfusion has the potential to change ... A randomized control trial of normothermic machine perfusion with 220 patients showed improvement of graft injury by 50%, even with a 50% lower ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8400594/

Normothermic Machine Perfusion (NMP) of the Liver Still, these results indicate that long-term NMP is safe and feasible [10]. ... Low ATP levels have been shown to correlate with poorer post- ...

8. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2817111

US Liver Transplant Outcomes After Normothermic ... Results suggest that NRP improves DCD liver allograft outcomes and has the potential to increase DCD organ use.