Machine Perfusion for Liver Transplant

(PILOT™_CA Trial)

Recruiting at 3 trial locations

Overseen By Stan Harris

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Organ Recovery Systems, Inc.

Disqualifiers: Multi-organ transplant, ABO incompatible, Severe infection, HIV positive, Acute liver failure, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for preserving livers before transplantation using the LifePort® Liver Transporter System. The goal is to determine if this machine can maintain donated livers in better condition, making transplants safer and more successful. Individuals waiting for their first liver transplant and listed on the United Network for Organ Sharing (UNOS) might be suitable candidates. Those informed of their need for a liver transplant and already on the official waiting list may find this trial relevant. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance liver transplant outcomes.

Do I need to stop taking my current medications for this trial?

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

What prior data suggests that the LifePort Liver Transporter System is safe for liver transplant?

Researchers are conducting studies to determine the safety of the LifePort Liver Transporter System for liver transplants. Initial tests in animals and humans have shown promising results. These studies focus on using the system to maintain liver health before transplantation. This process, known as hypothermic machine perfusion (HMP), involves keeping the liver cold and supplying it with oxygen.

Evidence from previous studies suggests that this method can help reduce complications after transplantation. The primary goal has been to prevent early allograft dysfunction, ensuring the liver functions well soon after the transplant. However, since the LifePort Liver Transporter is still seeking approval for clinical use, more data is needed to fully understand its safety. This trial aims to gather additional information to support its safe use in future treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional methods for preserving livers for transplant, which often involve static cold storage, the LifePort® Liver Transporter System uses hypothermic machine perfusion. This technique pumps a cold, oxygenated solution through the liver, potentially reducing damage and improving the organ's viability before transplantation. Researchers are excited about this approach because it could enhance liver function and increase the success rate of transplants, addressing some of the limitations of current preservation methods.

What evidence suggests that the LifePort Liver Transporter System is effective for liver transplant?

Research has shown that the LifePort® Liver Transporter System, used in this trial, employs a cooling method called hypothermic machine perfusion (HMP) to enhance liver transplant outcomes. Studies have found that livers preserved with this system encounter fewer complications shortly after surgery. Patients receiving these livers also spent less time in the hospital compared to those with livers stored using the traditional cold method. This system maintains the liver in a more oxygen-rich and stable environment, which appears to preserve the organ's health before transplant. Overall, these findings suggest that the LifePort system could improve the safety and success of liver transplants. ^{1 2 3 6 7}

Who Is on the Research Team?

Stan Harris

Principal Investigator

Organ Recovery Systems

Matthew Copithorne

Principal Investigator

Organ Recovery Systems

Are You a Good Fit for This Trial?

This trial is for adults over 18 who need a new liver and are on the UNOS waiting list. They must be first-time transplant recipients, not have HIV, severe infections, or acute liver failure. Pregnant individuals or those getting multiple organ transplants can't participate.

Inclusion Criteria

I am on the UNOS waiting list for a liver transplant.

I have received a liver transplant for the first time.

Written informed consent required

Exclusion Criteria

My blood type does not match the donor liver's blood type.

I am experiencing sudden severe liver failure.

I have received multiple organ transplants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo hypothermic machine perfusion with the LifePort Liver Transporter system

Immediate

Follow-up

Participants are monitored for early allograft dysfunction and other safety outcomes

7 days

What Are the Treatments Tested in This Trial?

Interventions

• LifePort® Liver Transporter System

Trial Overview

The study tests the LifePort Liver Transporter System's performance in preserving livers for transplant through Hypothermic Machine Perfusion—a way to keep organs cold while supplying them with nutrients and oxygen before surgery.

How Is the Trial Designed?

Group I: Hypothermic Machine Perfusion Experimental Treatment 1 Intervention

Hypothermic Machine Perfusion with Organ Recovery Systems LifePort Liver Transporter system

Who Is Running the Clinical Trial?

Organ Recovery Systems, Inc.

Lead Sponsor

Trials

2

Recruited

260+

Published Research Related to This Trial

The use of left ventricular assist devices (LVADs) has become a standard treatment for patients with end-stage heart failure, particularly for those awaiting organ transplants or who cannot undergo transplantation.

This report highlights the longest documented duration of LVAD support using the Jarvik 2000 device, emphasizing the variability in treatment duration and the potential for LVADs to serve as effective bridges to transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longest reported support (7.5 years) with postauricular type of Jarvik 2000 axial-flow left ventricular assist device. Martin-Suarez, S., Fiorentino, M., Loforte, A., et al.[2022]

In a study of 382 patients with the HeartWare left ventricular assist device (HVAD), pump thrombus occurred in 8.1% of patients, highlighting it as a significant adverse event with a rate of 0.08 events per patient-year.

Key risk factors for developing pump thrombus included high mean arterial pressure, low aspirin dosage, inadequate anticoagulation, and specific patient profiles, suggesting that better management of these factors could reduce thrombus rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial. Najjar, SS., Slaughter, MS., Pagani, FD., et al.[2022]

The Edwards SAPIEN transcatheter heart valve (THV) is considered noninferior to traditional surgical aortic valve replacement for high-risk operable patients, based on the high-risk arm of the PARTNER trial.

Despite some concerns about safety and trial misconduct, the FDA panel unanimously agreed that the benefits of the Edwards SAPIEN THV outweigh the risks, leading to its approval for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the 2012 Food and Drug Administration Circulatory System Devices Panel of the Medical Devices Advisory Committee meeting on the Edwards SAPIEN transcatheter heart valve for high-risk aortic stenosis patients. Barbash, IM., Dvir, D., Waksman, R.[2013]

The SAPIEN XT transcatheter heart valve system is associated with significantly fewer overall and major vascular complications compared to the original SAPIEN system, making it a safer option for patients with severe aortic stenosis who cannot undergo surgery.

Both SAPIEN and SAPIEN XT systems showed similar effectiveness in reducing all-cause mortality, major stroke, and rehospitalization rates at one year, indicating that the newer SAPIEN XT system maintains therapeutic efficacy while improving safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Evaluation of the SAPIEN XT Transcatheter Heart Valve System in Patients With Aortic Stenosis Who Are Not Candidates for Surgery. Webb, JG., Doshi, D., Mack, MJ., et al.[2022]

The Liotta low profile porcine bioprosthesis (LBP) was studied in 25 surgical explants over a mean period of 95 months, revealing that valve regurgitation is the primary failure mode, primarily due to commissural tearing.

Commissural tearing, especially of the right coronary cusp, was the most common cause of regurgitation, indicating that the low profile design may increase stress at the commissures, leading to accelerated calcification and failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-profile porcine bioprosthesis (Liotta): pathologic findings and mode of failure in the long-term. Ius, P., Thiene, G., Minarini, M., et al.[2006]

In a study of 318 patients who received the Edwards Lifesciences Prima Plus stentless valve for aortic valve replacement, the 10-year survival rate was 33%, indicating that the valve provides good long-term outcomes.

The ELSV showed excellent performance with 100% freedom from valve reoperation and 64% freedom from structural valve deterioration at 10 years, suggesting its durability and effectiveness in preventing major complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of aortic valve replacement with Edwards Prima Plus stentless bioprosthesis: eleven years' follow up. Auriemma, S., D'Onofrio, A., Brunelli, M., et al.[2022]

The less-invasive implantation technique for the HeartMate 3 left ventricular assist device (LVAD) using an upper hemi-sternotomy and anterior lateral thoracotomy has been shown to be technically feasible, resulting in reduced surgical trauma and postoperative complications.

This approach leads to benefits such as less postoperative bleeding, decreased need for blood transfusions, and quicker recovery times, suggesting it may become the standard method for LVAD implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Less invasive HeartMate 3 left ventricular assist device implantation. Schmitto, JD., Krabatsch, T., Damme, L., et al.[2022]

In a study of 50 patients with advanced heart failure, the HeartMate 3 left ventricular assist system (LVAS) demonstrated a high 6-month survival rate of 92%, exceeding the performance goal of 88%, and significantly reduced mortality risk by 66% compared to predicted survival rates.

The LVAS was found to be safe with a favorable adverse event profile, showing no pump malfunctions or thrombosis, and led to improvements in quality of life and functional status, as measured by various health assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fully Magnetically Levitated Left Ventricular Assist System for Treating Advanced HF: A Multicenter Study. Netuka, I., Sood, P., Pya, Y., et al.[2022]

In a study of 235 patients with severe aortic stenosis, the use of the Edwards Sapien 3 valve for transcatheter aortic valve implantation (TAVI) resulted in no cases of moderate or severe residual aortic regurgitation, indicating high device success.

The procedure, performed without general anesthesia, showed low rates of major vascular complications (3.0%), mortality (2.6%), and stroke (2.1%) within 30 days, demonstrating its safety and efficacy across different valve sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfemoral Aortic Valve Implantation with the New Edwards Sapien 3 Valve for Treatment of Severe Aortic Stenosis-Impact of Valve Size in a Single Center Experience. Wöhrle, J., Gonska, B., Rodewald, C., et al.[2019]

The Left Ventricular Assist Device (LVAD), approved by the USFDA in 1998, has been effective in significantly improving the health of patients with cardiomyopathies and congestive heart failure (CHF) by restoring normal blood flow and hemodynamics.

Recent studies suggest that the LVAD could serve as a long-term treatment option (destination therapy) for patients, potentially reducing the need for heart transplants and addressing the shortage of available donor hearts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The left ventricular assist device (LVAD). A bridge to heart transplantation. Camp, D.[2017]

The heart transplantation program at the National Cerebral and Cardiovascular Center has achieved a remarkable 10-year survival rate of 93.4% among 50 patients, with two individuals thriving for over 13 years post-transplant.

The center has transitioned to using implantable left ventricular assist systems (LVAS) as the primary option for bridging patients to transplantation, following the approval of these devices by medical insurance in 2011, after previously using extracorporeal LVAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Heart transplantation and ventricular assit systems]. Nakatani, T., Hata, H., Fujita, T., et al.[2013]

In a study of 569 patients listed for heart transplant, those supported by the HeartMate III (HM3) and HeartWare HVAD (HVAD) devices showed similar 1-year mortality rates of 20% and 17%, respectively, indicating comparable safety profiles for these LVADs.

Post-transplant survival rates were also similar, with 1-year survival at 97% for HM3 and 94% for HVAD, suggesting that both devices are effective options for patients awaiting heart transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Tale of Two Centrifugal-Flow Ventricular Assist Devices As Bridge to Heart Transplant. Alwair, H., Whitehouse, K., Slaughter, MS., et al.[2022]

Long-term left-ventricular assist devices (LVADs) are emerging as a viable destination therapy for patients with advanced heart failure, providing a new treatment option for this growing patient population.

The article reviews the clinical trials that supported LVAD approval, outlines national policies for patient selection, and discusses the outcomes associated with this therapy, emphasizing the importance of proper candidate assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Destination therapy: patient selection and current outcomes. Lietz, K.[2022]

The Jarvik 2000 axial flow left ventricular assist system (LVAS) was successfully implanted in 22 patients, showing significant improvements in hemodynamic function, with a 70.6% increase in cardiac index and a 44% decrease in pulmonary capillary wedge pressure within 48 hours after implantation.

The device can be safely used as a bridge to transplant or as destination therapy, with patients showing improved heart function and quality of life, as evidenced by most patients achieving NYHA class 1 status after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of the Jarvik 2000 left ventricular assist system as a bridge to heart transplantation or as destination therapy for patients with chronic heart failure. Frazier, OH., Myers, TJ., Westaby, S., et al.[2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03484455

NCT03484455 | Study to Evaluate Performance of the ...

Study to Evaluate Performance of the Organ Recovery Systems LifePort® Liver Transporter System, a Machine Perfusion System, for Liver Transplant (PILOT™).

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11019979/

Portable hypothermic oxygenated machine perfusion for ...

HMP-O2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction.

3.

organ-recovery.com

organ-recovery.com/lifeport-liver-transporter/

LifePort Liver Transporter

Additionally, patients receiving LifePort perfused livers had a significantly lower length of hospital stay than patients with static cold stored livers (10.9 ± ...

4.

organdonationalliance.org

organdonationalliance.org/case-study/organ-procurement-organization-utilization-of-portable-hypothermic-oxygenated-machine-perfusion-in-liver-transplantation-the-first-us-experience/

Case Studies

The Approach. The LifePort Liver Transporter (LLT) is a portable HMP-O2 platform currently being utilized under a continued access clinical trial (NCT05574361).

5.

frontierspartnerships.org

frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2024.12853/full

Transplant Trial Watch - Frontiers Publishing Partnerships

The key strength of this work is that 43% (n = 27) of the HMP-O2 livers had continuous perfusion, having been placed on device at the donor.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10965685/

Transplant Trial Watch - PMC

The Transplant Trial Watch is a monthly overview of 10 new randomised controlled trials (RCTs) and systematic reviews.

7.

links.lww.com

links.lww.com/HEP/I164

STATISTICAL ANALYSIS PLAN

Initial testing of HMP use in liver transplantation in animals and humans shows promising results and warrants further investigation of the.