For investigators

Information for investigators around trial design, criteria and outcomes.

Study hypothesis

Does the availability of normothermic machine perfusion in extended criteria livers improve utilisation without compromising outcome?

Eligibility criteria

Participant inclusion criteria 

Liver offers:

• Deceased organ donors aged 16 years or over
• Offered through the national offering scheme
• Donor Utilisation Index (DUI) greater than 0.27

Livers undergoing normothermic regional perfusion (NRP) will be included in the study and use of NRP corrected for in analysis.

Liver transplant recipients:

• Recipients 18 years of age or above
• Elective and super-urgent
• Participant is willing and able to give informed consent for participation in the study

Participant exclusion criteria

Liver offers:

• Donors falling outside national offering scheme
• Donors where information about study participation was not sent with the organ offer
• Donors from outside of the UK
• Donor is HIV or hepatitis C positive
• Livers undergoing any other form of ex-vivo machine preservation
• Participating centre cannot offer NMP due to device, logistical or staffing reasons

Liver transplant recipients:

• Receipt of a liver that has not been recruited to the study
• Have not agreed to use of NMP according to local consent policy
• Receipt of a split liver transplant
• Receipt of a multi-organ transplant
• Transplanted outside of the 7 participating centres

Study Design

The PLUS study has a threshold-crossing design with a prospectively-defined efficacy threshold.

A real-world control cohort identified from the NHS Blood and Transplant registry, meeting study inclusion criteria in which normothermic machine perfusion (NMP) was not used.

A study cohort of prospectively identified, consecutive liver offers with a donor utilisation index >0.27* in which NMP is made available.

*A DUI of >0.27 represents the 60% least well utilised livers

Study outcomes

Primary outcome measure

Functional utilisation – transplantation of the liver with 12-month patient and graft survival

Secondary outcome measures

• Intervention costs, NHS resource use and quality of life
• Biochemical liver function
• Graft and patient survival
• Postoperative hospital resource
• Perfusion parameters, biomarkers in perfusion fluids and graft histology
• Safety outcomes

For more information about the study please contact our team at PLUS@nhsbt.nhs.uk.