In the past ten years, more than 45,000 organs recovered for transplantation were not used to save lives, according to data from the Organ Procurement and Transplantation Network.

Part of the organ discard rate can be attributed to prolonged cold ischemic time, which is the time that an organ spends outside the body between procurement and transplantation. “Cold ischemic time not only limits how far an organ can travel, it is also linked with higher rates of organs being declined by transplant hospitals,” said United Network for Organ Sharing data science manager Andrew Placona. Each organ possesses its own cold ischemic time limit. While kidneys can typically survive outside the body for 24 to 36 hours, livers, intestines and pancreata only last on average for about 12 to 18 hours. Hearts and lungs have even shorter cold ischemic time limits, typically lasting outside the body for four to six hours on average.

“Speedier transportation will result in more organs transplanted, more lives saved and more improved long-term outcomes for transplant recipients,” explained Placona, who is serving as principal investigator on research that aims to help organ procurement organization, or OPO, professionals make more informed decisions about optimal travel routes for procured organs.

A joint effort

Partnering with seven OPOs across the country—along with the travel companies they enlist to help transport organs—Placona’s team is conducting real-time data analysis to refine a feasibility algorithm aimed at predicting the optimal route for organ transplantation.

Describing the algorithm as an Expedia-like application that OPO and transplant hospital professionals can use to choose the best route for an organ, Placona said he envisions people using the application to make informed decisions about optimal travel methods for organs and then tracking the organs in real time as they make their way from the donor hospital to the transplant hospital.

“This project addresses a complex problem in organ transplantation, mainly coordinating logistics for organ transport and understanding the components of cold ischemic time,” said Jeffrey Orlowski, president and CEO of LifeShare Transplant Donor Services of Oklahoma, which is the organ recovery organization for the state of Oklahoma.

Beginning December 2019, the UNOS information technology team began assessing the feasibility of building application programming interfaces that will act as bridges between the OPOs’ transportation vendor databases and UNOS’ systems to enable the flow of data between the applications. The feasibility study will continue through August 2020.

The other portion of the project involves analysis to determine if the collected data can contribute to the existing feasibility algorithm, which combines major airline and limited charter availability with current drive times to potentially determine the most efficient travel options at any given moment. The research is being conducted through UNOS Labs^SM, which is an experimental incubator that unites data, technology and industry expertise to test transformational ideas and hypotheses for improving the transplant system.

“With a better understanding of how transit time impacts cold ischemic time, we could potentially assign an estimated cold ischemic time upon arrival into UNet,” explained Placona. UNet^SM is UNOS’ electronic network that allows transplant professionals to register transplant candidates on the national organ waiting list, match the candidates with donated organs and enter vital medical data on candidates, donors and transplant recipients. “This would allow for more informed organ offer considerations.”

Using big data to solve complex problems

In the future, the research team plans to expand the algorithm to incorporate additional data inputs, such as weather, flight cargo limits and expanded charter flight availability. They also plan to validate the model using previously planned organ travel information, collaborating with courier services and OPOs. After validating the model, UNOS will create a user-friendly application that will enable piloting of the algorithm with more OPOs.

“In our line of work, time is critical and lives depend on timely response,” Orlowski said. “This project explores solutions to organ transportation and will help optimize travel and troubleshoot for weather, traffic and flight changes in real time.”

Placona expects the project to eventually result in reduced prolonged cold ischemic time and enable better transplant outcomes, including reducing organ discards and rejections. “Ultimately, our goal is to increase organ utilization and improve outcomes for patients,” he said. “If we can use data science to figure out where the inefficiencies are in the organ procurement process, then we can start finding solutions.”

Organ Recovery Systems founder and CEO David Kravitz has more than a professional interest in transplantation. In the 1990s while the entrepreneur was running a company under contract with the U.S. military to improve battlefield trauma care, his own father ended up needing a heart transplant.

At the time Kravitz had no experience with organ transplantation, so he was astonished to learn that the heart that would save his father’s life could only come from within a few hours’ distance and would “show up in a beer cooler,” he said. “I just couldn’t quite believe it, and the doctors were telling me that was the state-of-the-art.”

Kravitz was sure there had to be a better way to protect and preserve an organ in transit. For years his efforts had been focused on trying to use interventional hypothermia — deliberately lowering a patient’s body temperature — to protect the brain from neurological complications following battlefield trauma. Drawing on this work, he conceived an interventional hypothermia-inspired design for a mechanized organ transporter. “The original vision was to enhance portability and preservation, keeping the organ alive and sustained so it could travel longer and be healthier,” he said.

From idea to action

A company focused on organ preservation products and services, Organ Recovery Systems was formed to develop the interventional hypothermia-inspired organ transporter concept. In the early 2000s the company’s LifePort Kidney Transporter, a transportable device for hypothermic machine perfusion, or HMP, gained Food and Drug Administration approval. Unlike normothermic preservation, which preserves organs at normal physiological temperatures, or static cold storage, which chills organs in a preservation solution in an ice box, hypothermic machine perfusion pumps a preservation solution continuously through the organ at temperatures between 1 and 10 degrees Celsius.

Today LifePort Kidney Transporter is routinely used in more than 300 transplant programs in 39 countries, with a performance record of more than 112,000 kidney transplant procedures. In France, LifePort Kidney Transporter has been specified as the HMP standard of care nationwide, from donor to recipient bedside, and is used in the majority of deceased donor kidney transplantation surgeries performed in that country.

Compounding success

Building upon the success of LifePort Kidney Transporter, Organ Recovery Systems researchers began developing a second LifePort system for livers, completing the first commercial-built prototype in 2016. As part of the FDA registration process, LifePort Liver Transporter is now in a phase three pivotal non-inferiority clinical trial comparing HMP to static cold storage. Phase three clinical trials compare two or more competing therapies. While most phase three trials aim to demonstrate the superiority of a new treatment in comparison with a control treatment, non-inferiority phase three trials assess if a more convenient, less toxic, or more affordable intervention is at least as efficacious as an existing standard of care.

“Our primary endpoint for the trial is early allograft dysfunction, based on how the liver functions in the first seven days after transplant,” said James Guarrera, M.D., who directs the liver transplantation program at University Hospital in Newark, New Jersey, and serves as co-lead investigator for the LifePort Liver Transporter clinical trial. “We are following patients out to a year, because a one-year graft survival time point is such an important metric in the U.S.,” he said. With those results, Guarrera says that transplant professionals will be able to “really take a critical look at the technology and then decide if they want to utilize it.”

Guarrera has been researching the potential of HMP for liver transplantation for nearly two decades. As a faculty member at Columbia University in 2010, he was lead author on the first published human prospective trial of liver HMP. The pilot study conducted at Columbia University used a prototyped perfusion system developed by the Columbia research team to reduce early allograft dysfunction in the HMP livers compared to static cold storage livers. Though these were small and non-randomized studies, the researchers demonstrated “a reduction in ischemia reperfusion injury, a reduction in early allograft dysfunction, less biliary complications and a shorter length of stay in the hospital,” Guarrera said. That research helped form the clinical basis for Organ Recovery Systems’ LifePort Liver Transporter.

Continuous improvement

Beyond ease of use, the LifePort Liver Transporter offers a benefit to transplant teams in its portability. Weighing about 100 pounds when fully loaded, it can be handled by two people. Already in the current clinical trial, livers have flown at least five times without issues.

“Functionality, in parallel with making sure that it was as transportable as possible, was really important,” Kravitz said.

 United Network for Organ Sharing chief medical officer David Klassen, M.D., expects research to eventually reveal that any form of machine perfusion — normothermic or hypothermic — is superior to the current standard of static cold storage, but no research as of yet has conclusively compared normothermic to hypothermic or established a standard-of-care perfusion protocol. There is a growing body of evidence, however, that machine perfusion can safely extend preservation time. With allocation policies evolving to promote broader geographic sharing, organs are likely to continue traveling longer over greater distances. Particularly for the most time-sensitive organs, such as livers, “this technology has big implications for allocation policy,” Klassen said.

It is in the longer distances and travel times made possible by HMP that Guarrera believes LifePort Liver Transporter offers a potential benefit. Additionally, in the event of technical failure, LifePort Liver Transporter is designed to fail safely, and still function as an effective static cold storage device. “You have the safety of that gold standard backup of cold storage,” Guarrera said. “As we are potentially sending livers over longer distances or don’t have experienced teams going with the organ, that is going to be a huge plus.”

For Kravitz, the experience of his own father’s transplant continues to inspire Organ Recovery Systems’ mission, which is focused on improving outcomes, lowering the cost of transplantation and honoring the gift of life. “It’s a passion for us, not a job,” he said.

In this series of videos, you’ll hear from Organ Center Director Roger Brown as he talks about how his staff works with the donation and transplant community to meet the daily challenge of matching organs and saving lives. Plus, how OC staff are trained, what motivates them, and the story of a 1-in-1,000 chance connection that gave a struggling firefighter a long-awaited chance for a longer life.