Title: Normothermic machine perfusion of transplant donor livers: making every donation count
Funder: Department of Health and Social Care

Abstract: The disparity between the liver transplant waiting list and the availability of donor organs means that there is an urgent need for technologies with the potential to improve the utilisation of livers. Utilisation of livers from higher risk donors is currently poor (around 19%) with many of these livers discarded due to uncertainty as to their suitability for transplant. Previous clinical trials have suggested that normothermic machine preservation (NMP) may reduce injury and improve viability assessment, resulting in an increase in the proportion of these donor livers successfully transplanted. The aim of this study is to assess the impact of the availability of NMP on the utilisation of livers from high-risk donors. Livers will be randomised to NMP or conventional static cold storage (SCS) at the time of organ offering, and the effect of the preservation method on subsequent acceptance and transplantation will be assessed. The primary endpoint will be the proportion of organs transplanted with function at 12 months. Secondary endpoints will include graft function, patient and graft survival, hospital and ITU stay and other NHS resource use. A health economic analysis will evaluate the cost, value for money and budget impact of NMP versus SCS from an NHS perspective. The proposed study duration is 42 months: 6 months set-up, 18 months recruitment, 12 months follow-up and 6 months reporting/dissemination. This study should provide the evidence needed to determine whether NMP should be adopted for routine use in the NHS, and help to inform the pricing model and adoption strategy required to make this possible. Outcomes from the study will be disseminated via peer-reviewed publications and conference presentations, as well as communicated to patient groups in lay language. These will also be provided to key NHS bodies and decision makers including NICE, NHSBT and NHS England.

Lay abstract: Liver transplantation is a highly effective treatment but there are not enough livers from deceased organ donors to meet the need of patients. More than 10% of patients on the waiting list die before receiving a transplant and many others are never placed on the list because access is restricted to patients with the best chance of success. Less than 2/3 of organ donors in the UK result in a liver transplant. Livers from many donors are less suitable, for reasons such as the donor s older age, medical conditions or circumstances of death, and are much more likely to cause complications. To use these higher-risk livers safely, we need to find better ways to preserve, repair and test donated livers so that more of the available donor organs can be transplanted without compromising the outcome for the recipient. Once removed from a donor, organs are stored in an ice box to reduce damage until transplant. Normothermic machine perfusion (NMP) is a method of organ preservation which replaces the icebox, using a machine which pumps blood at body temperature into the liver during storage. The allows us to assess how well the liver is working, reduces the injury to the liver and allows repair of the organ before transplant. Previous studies have shown that this technique reduces injury to the liver. These also suggested that transplant surgeons could accept higher risk organs with confidence, mainly because they can assess function before transplant. However, these studies were not designed to test the effects of NMP on organ use, and there is still a need for high-quality evidence as to whether this more complex and expensive technology should be used routinely. The UK-designed and manufactured NMP device which will be used in this study has already been used in small numbers of transplants in UK liver transplant units. As NMP technology is not yet funded by the NHS, the money to pay for this has mostly come from charities. In this trial, we will randomly assign offers of high-risk donor livers to be stored either cold or on the NMP machine. We will then see how many in each group result in a successful transplant. We will also collect information about the overall cost compared to storage on ice, so that the NHS can decide whether any benefits of the new machine justify the cost. Patients and their families have been involved in the design of this study and will be included on the committee that runs it. They believe this to be an extremely important area for research. NHS Trusts, NHSBT and NHS England have been consulted and are in strong support of this study.

Research activity codes: 6.4 SURGERY
Health categories: ORAL AND GASTROINTESTINAL