Portable hypothermic oxygenated machine perfusion for organ preservation in liver transplantation: A randomized, open-label, clinical trial

Abstract

Background & Aims: In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic Oxygenated Machine Perfusion (HMP-O2) has shown benefit compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O2 device in the first US randomized control trial. Approach & Results: The PILOT™ trial (NCT03484455) was a multicenter, randomized, open-label, non-inferiority trial, with participants randomized to HMP-O2 or SCS. HMP-O2 livers were preserved using the Lifeport® Liver Transporter and Vasosol® perfusion solution. Primary outcome was early allograft dysfunction (EAD). Non-inferiority margin was 7.5%. From 4/3/19-7/12/22, 179 patients were randomized to HMP-O2 (n=90) or SCS (n=89). Per protocol cohort included 63 HMP-O2 and 73 SCS. EAD occurred in 11.1% HMP-O2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. Risk of graft failure as predicted by L-GrAFT7 was lower with HMP-O2 (median [IQR] 3.4% [2.4-6.5] vs. 4.5% [2.9-9.4], p=0.024). 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). Conclusions: HMP-O2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. EAD by L-GrAFT7 was lower in HMP-O2, suggesting improved early clinical function. Recipients of HMP-O2 livers also demonstrated a lower incidence PNF and biliary strictures, although this difference did not reach significance.