Clinical and technical evidence
A literature search was carried out for this briefing in accordance with the interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting firstname.lastname@example.org.
There are 6 studies summarised in this briefing, including 483 livers. Five studies were prospective non‑randomised clinical studies and 1 was a randomised controlled trial.
The evidence base for the technology is of moderate methodological quality.
Three of these studies are based in the UK NHS. All clinical studies suggest that the device may help increase the number of donor livers that can be successfully transplanted.
Further evidence would benefit from sufficiently powered sample sizes, use of high-risk organs, randomisation at time of organ donation and appropriate long-term follow ups to improve the evidence base. No studies were found that showed the benefit of the OrganOx metra compared with other machine perfusion devices.
Livers were randomised into 2 arms: normothermic machine perfusion (NMP) using the OrganOx metra, and static cold storage (SCS). The results showed that the organ discard rate was statistically significant between groups. The SCS group had a 24.1% discard rate and NMP had a 11.7% discard rate. There was a significant reduction in peak aspartate aminotransferase and early allograft dysfunction rates in NMP livers compared with the SCS group.
Ten donor livers that were considered unsuitable for transplant had 4 hours of perfusion using OrganOx metra. Graft viability was reassessed using haemodynamic, metabolic and synthetic parameters. All 10 were then considered acceptable and since transplant they all function satisfactorily.
The primary outcome measure was safety as defined by 30‑day patient and graft survival. Secondary outcomes included 90‑day graft survival; incidence of early allograft dysfunction; and biliary and arterial complications at 6 months. Results showed no difference in graft function, incidence of complications or graft and patient survival in back-to-base approach compared with immediate NMP.
The primary end point was to test the safety and feasibility of the post-SCS normothermic perfusion approach. Results showed a 94% 30‑day graft survival rate, supporting safety and feasibility of the device. Secondary end points included early allograft dysfunction, need for renal replacement therapy and adverse events.
From 34 donor livers, 9 were discarded because of poor performance during NMP. There were 25 organs successfully transplanted after preservation of up to 38 hours. Extended criteria donor rates were 100% and 92% in discarded and transplanted livers. Graft and patient survival at 20 months was 88%.
There were 31 discarded livers assessed using OrganOx metra, and 22 (71%) were found to meet viability criteria and were transplanted. Viability testing with NMP allowed successful transplantation of 71% of discarded livers, with 100% 90‑day patient and graft survival. There were 4 individuals who developed biliary structures that needed re-transplantation.
Using ex-vivo normothermic machine perfusion with the OrganOx metra device to store human livers for transplantation. ClinicalTrials identifier: NCT02478151. Status: enrolling by invitation. Indication: end-stage liver disease. Device: OrganOx metra. Estimated study completion date: September 2021. Country: Canada.
RESTORE declined livers study. Trial identifier: NCT04483102. Status: recruiting. Indication: liver diseases, surgery, and transplant; failure, liver. Device: OrganOx metra. Estimated study completion date: September 2022. Country: US.
Normothermic liver preservation trial. Trial identifier: NCT03089840. Status: recruiting. Indication: end-stage liver disease or liver diseases. Device: OrganOx metra. Estimated study completion date: June 2022. Country: Canada.
Hypothermic oxygenated (HOPE) versus NMP in human liver transplantation (HOPE-NMP). Trial identifier: NCT04644744. Status: recruiting. Indication: hepatocellular injury or liver transplant disorder. Devices: HOPE or NMP. Estimated study completion date: December 2024. Country: Germany.
WP01 - normothermic liver preservation. Trial identifier: NCT02775162. Status: completed. Indication: liver transplantation. Device: NMP. Completion date: February 2021. Country: US.
NAPLES study (normothermic machine perfusion of the liver to enable the sickest first). Status: preliminary results, ongoing study. Indication: liver transplant. Device: NMP. Country: UK.