Extract

Background and study aims There is a nationwide shortage of livers for transplantation. The OrganOx Metra machine has been developed and investigated to maintain a liver at normal body temperature prior to transplantation. It is hoped that using normothermic preservation will help to improve the quality of livers when they are transplanted and may mean that more organs become suitable for use in liver transplantation. The safety of this device has been demonstrated, but any benefit in humans when compared to conventional storage on ice still remains to be seen. The purpose of this study is to compare normothermic machine perfusion (NMP) and cold storage (SCS). Who can participate? There are four liver transplant centres in England participating in this study, as well as three others in the EU. All patients meeting the inclusion / exclusion criteria currently on the waiting list for a liver transplant at any of these hospitals will be invited to participate in this study. Detailed information will be given both verbally and in the form of a Patient Information Leaflet. Patients will be given a minimum of 24 hours (if required) to consider the information before deciding whether to give written consent to participation. A list of consenting patients will be maintained by the study coordinator and the liver transplant coordinators. What does the study involve? All organs which fulfil the entry criteria and are accepted for transplantation using the criteria used by the participating transplant units will be included. When a suitable donor organ becomes available and this is allocated to a recipient patient who has provided consent, then the recipient will be asked to affirm the consent that has already been provided by signing and dating the Informed Consent Form for a second time. This process may also be done with a documented phone call. If the patient is not willing to proceed in the study at this stage, then the patient will not be included in the trial and the organ retrieval and preservation will be carried out using conventional procedures. If the patient is willing to proceed with the study and, if the OrganOx metra machine and team are available, then the recipient transplant coordinator will enter the required baseline details about the donor and recipient into the secure online electronic database, which will then randomise (allocate in a random fashion like tossing a coin) the liver to either machine perfusion (NMP) or cold storage (SCS). A total of 260 donor livers will be included in this study, 130 in each group. If the liver is allocated to the SCS group then the organ retrieval, preservation, transport and implantation will proceed in the conventional manner, with the liver stored in an ice box. If the liver is allocated to the NMP group then the OrganOx metra machine and team will travel to the retrieval hospital at the same time as the organ retrieval team. The organ retrieval will proceed in the conventional manner until the liver has been removed from the donor. No aspect of the donor management will be altered by involvement in this study. The only change in management occurs in the preservation of the liver once it has been removed from the donor. After removal from the donor, the liver will be flushed with a cold preservation solution, prepared on the backtable, cannulated and then attached to the machine where it is perfused with blood, oxygen and nutrients, as well as some medications, at normal body temperature. It will remain on this machine during transport to the recipient transplant centre and during the transplant operation itself until the transplant surgeon is ready to transfer the liver from the machine into the recipient. At this point the liver is removed from the device, flushed with a cold solution and then transplanted in the conventional manner. After the transplant, the patient will be treated according to the standard clinical protocols of the respective transplant unit. Data will be collected at the timepoints identified in the Study Schedule below. The only study-specific investigations (requiring an intervention not otherwise stipulated for clinical reasons) will be a quality of life (EQ5D5L) and health economic questionnaire and an MRCP (magnetic resonance cholangiopancreatogram) scan. In some of the participating transplant centres this scan is standard clinical practice whilst in others this will be done specifically for the trial. Study Schedule for all participants: - Demographic donor data. - 2 liver biopsies will be taken during the preservation process, and 1 after implantation. - Intraoperative blood pressure changes will be recorded at the time of organ implantation (post-reperfusion syndrome). - Liver function tests (bilirubin, AST, gammaGT, INR and lactate) will be measured on days 1-7 post-operatively. These will not involve any additional study-specific samples. These tests will be measured and recorded again at day 30 and 6, 12 and 24 months postoperatively. Throughout the study period we will record graft and patient survival. A baseline quality of life questionnaire (EQ5d5L) will be recorded preoperatively. This will be repeated, along with a resource use questionnaire, at day 30 and 6 months postoperatively. An MRCP will be performed 6 months postoperatively looking for ischaemic cholangiopathy. Additional samples will be taken from NMP livers whilst they are on the OrganOx metra: - Perfusion blood samples (approximately 5mls) from the machine at 15mins, 1hour and the end of preservation. - A sample of the bile produced by the liver whilst on the machine An additional tick box is included on the consent form for samples to be taken for the Oxford Radcliffe Bioresource. If participants have consented to this, additional blood and urine samples will be taken from the recipient during the transplant. If participants have not consented to this, they will still be included in the trial but these specific samples will not be taken. What are the possible benefits and risks of participating? Participation in this trial will not affect a patient’s position on the liver transplant waiting list or their likelihood of receiving a liver transplant. Similarly, withdrawal of a participant from the trial at any point and for any reason will not affect their position on the liver transplant waiting list or their likelihood or receiving a liver transplant. Where is the study run from? Four liver transplant centres in England participating in this study (King's College Hospital, London; Royal Free Hospital, London; Queen Elizabeth Hospital, Birmingham; and Addenbrooke's Hospital, Cambridge), as well as three others in the EU (Belgium, Germany and Spain). When is the study starting and how long is it expected to run for? April 2014 to September Who is funding the study? European Commission Seventh Framework Programme (FP7) Who is the main contact? Prof Peter Friend [email protected]

Inclusion criteria

• We are studying the effect of using normothermic liver perfusion to preserve the donor liver on the outcomes of liver transplantation. The disease common to all the recipients is end-stage liver failure

Links

• ictrp
• isrctn