Normothermic Machine Perfusion for Liver Transplant

Overseen By Heidi Yeh, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Massachusetts General Hospital

Disqualifiers: Cardiac, Pulmonary, Prior liver transplant, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to assess the ability of Normothermic Machine Perfusion (NMP) to resuscitate moderately steatotic livers for transplantation in patients. This will be a single-site clinical trial placing donor livers with 30-60% macrosteatosis on NMP, and then transplanting those that meet commonly accepted viability criteria. The results of this study could lead to a trial extending NMP transplantation to severely steatotic livers, further expanding the donor organ pool.

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 data supports the effectiveness of the treatment Normothermic Machine Perfusion for liver transplant?

Normothermic Machine Perfusion (NMP) helps improve the condition of high-risk donor livers and reduces complications after transplant. It also allows for better assessment of the liver's health before transplant, potentially increasing the number of usable donor livers. ^{1 2 3 4 5}

Is Normothermic Machine Perfusion (NMP) safe for liver transplants?

Early clinical results suggest that Normothermic Machine Perfusion (NMP) is generally safe for liver transplants, as it helps preserve and potentially repair donor livers, reducing complications after surgery. ^{1 2 3 4 6}

How is the treatment Normothermic Machine Perfusion different from other liver transplant treatments?

Normothermic Machine Perfusion (NMP) is unique because it preserves the liver in a warm, functioning state outside the body, which can improve the condition of high-risk livers and expand the pool of usable donor organs compared to traditional cold storage methods. ^{1 2 3 4 7}

Eligibility Criteria

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

Calculated MELD-Na score <= 25

I am between 18 and 80 years old.

Listed for liver transplantation at MGH

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.

Trial Timeline

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

Treatment Details

Interventions

• Normothermic Machine Perfusion (Procedure)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

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]

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) 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) 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]

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) 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 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]

References

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

Normothermic liver preservation, current status and future directions. [2019]

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

From Patients to Providers: Assessing the Impact of Normothermic Machine Perfusion on Liver Transplant Practices in the US. [2023]

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

Making Every Liver Count: Increased Transplant Yield of Donor Livers Through Normothermic Machine Perfusion. [2021]

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

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

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

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

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

Impact of Temperature on Porcine Liver Machine Perfusion From Donors After Cardiac Death. [2017]

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

Normothermic ex-situ liver preservation: the new gold standard. [2018]