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Portable Hypothermic Oxygenated Machine Perfusion for Organ Preservation in Liver Transplantation (PILOT TM): A Randomized, Open-Label, Clinical Trial

28 Pages Posted: 17 Jul 2023

See all articles by Guergana G. Panayotova

Guergana G. Panayotova

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery

Keri Elizabeth Lunsford

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery

R. Cutler Quillin

University of Cincinnati - Division of Transplantation

Abbas Rana

Baylor University - Division of Abdominal Transplantation

Vatche G. Agopian

University of California, Los Angeles (UCLA) - Dumont-UCLA Transplant Center

Grace S. Lee-Riddle

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery

Daniela Markovic

University of California, Los Angeles (UCLA) - Division of General Internal Medicine

Flavio Paterno

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery

Adam D. Griesemer

New York University (NYU) - NYU Langone Transplant Institute

Arpit Amin

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery

Diane Alonso

Intermountain Medical Center - Liver Transplant Program

Juan P. Rocca

Cornell University - Division of Liver Transplantation and Hepatobiliary Surgery

Daniel Borja-Cacho

Northwestern University - Division of Organ Transplantation

Roberto Hernandez-Alejandro

University of Rochester - School of Medicine and Dentistry

John F. Fung

University of Chicago - Department of Surgery

Shawn J. Pelletier

University of Virginia - Division of Transplantation Surgery

Shimul A. Shah

University of Cincinnati - Division of Transplantation

James V. Guarrera

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery

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Abstract

Background: In liver transplantation (LT), cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic Oxygenated Machine Perfusion (HMP-O2) has shown benefit compared to static cold storage by limiting ischemia-reperfusion injury. This study reports outcomes for LT using a novel portable HMP-O2 device in the first US randomized control trial. 

Methods: The PILOT™ trial (NCT03484455) was a multicenter, randomized, open-label, non-inferiority trial enrolling at nine US LT centers. Participants were randomized to HMP-O2 or SCS at organ offer by computerized stratified randomization. Livers were preserved using the Lifeport® Liver Transporter and Vasosol® perfusion solution (HMP-O2) or cold storage on ice (SCS). Primary outcome was early allograft dysfunction (EAD). Per-protocol cohort was included in primary and safety analyses. Non-inferiority margin was 7·5%. 

Findings: From 4/3/19 to 7/12/22, 179 patients were randomized to HMP-O2 (n=90) or SCS (n=89). Per protocol cohort included 63 HMP-O2 (38 male, 25 female) and 73 SCS (47 male, 26 female). EAD occurred in 11·1% HMP-O2 (N=7, RR 0.68, 95%CI 0·28-1·56) and 16·4% SCS (N=12, RR 1·48, 95%CI 0·64-3·47, p=0·37). The 90% upper confidence limit showed 5·5% difference, establishing noninferiority. EAD was supplemented with risk of graft failure as predicted by L-GrAFT7, which was lower with HMP-O2 (3·4% vs. 4·5%, p=0·024). There was no device-related mortality. Primary nonfunction occurred in 2·2%, all SCS (n=3, p=0·10). Biliary strictures occurred in 16·4% SCS (n= 12) and 6·3% (n=4) HMP-O2 (p=0·18). Non-anastomotic biliary strictures occurred only in SCS (n=4). Adverse events were more frequent with SCS (p=0·029) and were more likely to occur within 30 days of transplant (p=0·011). 

Interpretation: HMP-O22 is a safe and effective liver graft preservation technique and is noninferior to SCS for liver preservation. Recipients of HMP-O2 livers exhibit a trend towards improved early clinical outcomes with fewer adverse events, including decreased EAD, PNF, and biliary strictures.

Trial Registration: The study was registered at clinicaltrials.gov with registration number NCT03484455.

Funding: This study was funded by Organ Recovery Systems (ORS, Itasca, IL).

Declaration of Interest: GG Panayotova – Unrelated research grant funding from the ASTS-Jon Fryer Resident Scientist Scholarship, and travel support for conference presentation from Organ Recovery Systems (ORS) KE Lunsford – Unrelated research grant funding from NIH NIDDK K08DK118187, NIH NCI R21CA267368, NIH NIDDK L30DK114972, New Jersey Health Foundation, the Feldstein Medical Foundation, and the American Society of Transplant Surgeons – Translational Genomic Institute. Consulting fees from GATT Technologies; Honorarium from the American Society of Transplantation. Scientific Society Leadership (unpaid) in the American Society of Transplant Surgeons (Vice Chair Elect to Surgeon Scientist Committee), American Society of Transplantation (COTS Executive Committee, LICOP Subcommittee Chair, Editorial Board Transplantation and Liver Transplantation. Stock ownership (unrelated) ROMTech, Johnson and Johnson, Henry Schein, Incyte, Intellia Therapeutics, and Tandem Diabetes. RC Quillin III - Travel payment and honorarium for RCT data presentation by ORS A Rana - No disclosures VAAgopian - Unrelated research grant funding NIH NCI R01CA255727, NIH NCI R01CA253651, NIH NCI R01CA204145, NIH NCI R01CA246304, NIH NCI R21CA240887, NIH NCI R21CA235340, NIH NCI U01CA230705, NIH NCI R01CA246329, NIH NCI R01CA246329 GS Lee-Riddle – Unrelated EBSCO-Dynamed; Honorarium-Rutgers University; Scientific Society Leadership (unpaid) AST PECOP D Markovic – No disclosures F Paterno – No disclosures A Griesemer – Site lead investigator for current clinical trial sponsored by ORS (paid to institution) A Amin – No disclosures D Alonso - Site lead investigator for current clinical trial sponsored by ORS (paid to institution) JP Rocca - Site lead investigator for current clinical trial sponsored by ORS (paid to institution) D Borja-Cacho - Site lead investigator for current clinical trial sponsored by ORS (paid to institution). Unrelated travel paid by Intuitive Surgical, Inc. R Hernandez-Alejandro – Site lead investigator for current clinical trial sponsored by ORS (paid to institution) JJ Fung - Site lead investigator for current clinical trial sponsored by ORS (paid to institution) SJ Pelletier - Site lead investigator for current clinical trial sponsored by ORS (paid to institution), unrelated Medical Director role in Lifenet Health SA Shah - Site lead investigator for current clinical trial sponsored by ORS (paid to institution), research funding from CareDx (paid to institution), Medical Advisory Board Genentech JV Guarrera – Lead investigator for current clinical trial sponsored by ORS (paid to institution), research grant funding by ORS (paid to institution), Consulting Fees from ORS and GATT Technologies, Travel support by ORS for conference presentation of trial results.

Ethical Approval: The study was conducted in compliance with U.S. Food and Drug Administration (FDA) regulations, guidelines for good clinical practice, and the ethical principles outlined in the Declaration of Helsinki. Institutional Review Board (IRB) approval was obtained through each individual center.

Keywords: Liver Transplantation, Organ Preservation, Ischemia Reperfusion Injury, Machine Perfusion, Hypothermic Oxygenated Machine Perfusion, Randomized Control Trial

Suggested Citation

Panayotova, Guergana G. and Lunsford, Keri Elizabeth and Quillin, R. Cutler and Rana, Abbas and Agopian, Vatche G. and Lee-Riddle, Grace S. and Markovic, Daniela and Paterno, Flavio and Griesemer, Adam D. and Amin, Arpit and Alonso, Diane and Rocca, Juan P. and Borja-Cacho, Daniel and Hernandez-Alejandro, Roberto and Fung, John F. and Pelletier, Shawn J. and Shah, Shimul A. and Guarrera, James V., Portable Hypothermic Oxygenated Machine Perfusion for Organ Preservation in Liver Transplantation (PILOT TM): A Randomized, Open-Label, Clinical Trial. Available at SSRN: https://ssrn.com/abstract=4507877 or http://dx.doi.org/10.2139/ssrn.4507877

Guergana G. Panayotova

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery ( email )

Keri Elizabeth Lunsford

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery ( email )

R. Cutler Quillin

University of Cincinnati - Division of Transplantation ( email )

Abbas Rana

Baylor University - Division of Abdominal Transplantation ( email )

Vatche G. Agopian

University of California, Los Angeles (UCLA) - Dumont-UCLA Transplant Center ( email )

Grace S. Lee-Riddle

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery ( email )

Daniela Markovic

University of California, Los Angeles (UCLA) - Division of General Internal Medicine ( email )

Los Angeles, CA
United States

Flavio Paterno

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery ( email )

Adam D. Griesemer

New York University (NYU) - NYU Langone Transplant Institute ( email )

Arpit Amin

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery ( email )

Diane Alonso

Intermountain Medical Center - Liver Transplant Program ( email )

Juan P. Rocca

Cornell University - Division of Liver Transplantation and Hepatobiliary Surgery ( email )

Daniel Borja-Cacho

Northwestern University - Division of Organ Transplantation ( email )

Roberto Hernandez-Alejandro

University of Rochester - School of Medicine and Dentistry ( email )

John F. Fung

University of Chicago - Department of Surgery ( email )

Chicago, IL
United States

Shawn J. Pelletier

University of Virginia - Division of Transplantation Surgery ( email )

Shimul A. Shah

University of Cincinnati - Division of Transplantation ( email )

James V. Guarrera (Contact Author)

Rutgers, The State University of New Jersey - Division of Transplant and HPB Surgery ( email )

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