Importance: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. Objective: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). Design, Setting, and Participants: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. Interventions: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. Main Outcomes and Measures: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. Results: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P =.01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P =.004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P =.007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P =.02) and 12 months (2.6% vs 9.9%; P =.02) after transplant. Conclusions and Relevance: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. Trial Registration: ClinicalTrials.gov Identifier: NCT02522871.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Mar 2022|
Bibliographical noteFunding Information:
Funding/Support: This study was supported by TranMedics Inc.
receiving personal fees from Intuitive Surgical outside the submitted work. Dr Pelletier reported receiving funding from Organ Recovery Systems outside the submitted work. Dr Lu reported receiving nonfinancial support from Tampa General Hospital during the conduct of the study. Dr Saharia reported receiving nonfinancial support from Houston Methodist Hospital during the conduct of the study. Dr Cigarroa reported receiving financial compensation from the Ford Foundation, Capital Group, Kleberg Foundation, and Clayton Foundation for Biomedical Research outside the submitted work. Dr MacConmara reported becoming employed by TransMedics after completion of the OCS Liver PROTECT randomized clinical trial and submission of the final manuscript. No other disclosures were reported.
© 2021 American Medical Association. All rights reserved.
PubMed: MeSH publication types
- Journal Article
- Multicenter Study
- Randomized Controlled Trial
- Research Support, Non-U.S. Gov't