Trials

Liver trial: normothermic machine perfusion vs. cold storage in liver transplants

 

This is a randomised controlled trial comparing the current standard method for preserving a liver (in an ice box - static cold storage (SCS)) with a new technique called normothermic machine perfusion (NMP). This technology has been developed by Prof Peter Friend and Prof Constantin Coussios at Oxford University and the device is produced by OrganOx Ltd. The technique involves perfusing a liver with oxygenated blood, nutrients and medications at normal body temperature to preserve the organ in a functioning, physiological state.

 

A total of 222 livers have been randomised to the trial to either SCS or NMP in seven transplant centres in the UK, Spain, Germany and Belgium. If randomised to SCS the livers were stored in an ice box as per standard care and the retrieval and transplant will proceed in the conventional manner. If the organ was randomised to NMP then it was placed on the OrganOx machine from the time of retrieval, throughout its storage and transport, until it was eventually transplanted.

 

The primary outcome measure for the trial is the peak transaminase level (AST) within seven days post-transplant. Many secondary outcomes are being recorded including graft survival and function, MRCP evidence of iscaemic cholangiopathy and a health economic analysis at 3 months, 6 months and 12 months patient follow-up.

 

On 9 March 2016, the last liver required to reach the recruitment target has been transplanted at the Queen Elizabeth Hospital in Birmingham (UK)! After that, the WP2 team has focused on gathering all patients' follow-up data at the pre-specified timepoints. the last included patient's 12 months follow-up was completed in March 2017 and with that last appointment, the data set for the COPE WP2 liver trial is complete for analysis. The team is working hard to publish our research results throughout the year 2017 and 2018 with more detailed sub-studies on sample analysis to follow beyond that timeframe.

 

POMP trial: oxygenated hypothermic kidney re-conditioning after cold storage

 

The objective of this randomised controlled trial is to evaluate pre-implantation reconditioning of donor kidneys from extended criteria donors (ECD) using oxygenated machine perfusion following cold storage. This study is led by Professor Andreas Paul from the University Clinic Essen in Germany and includes transplant centres in Germany, the UK, Belgium, The Netherlands and Hungary. The hypothermic trial device is provided by Organ Assist Products B.V. and the Centre for Evidence in Transplantation (University of Oxford, UK) has supported trial design and protocol development.

 

Once ECD donors are identified and randomisation is undertaken, the donor organ is placed in cold storage as per standard care irrespective of the randomisation outcome. However, if the kidney was randomised to hypothermic machine perfusion (HMP), it will be placed on the perfusion machine with oxygen for a minimum durtation of two hours prior to transplantation at the recipient centre. Kidneys randomised to static cold storage will stay in the standard care ice box without machine intervention until transplantation. The primary outcome measure in this project is death censored graft survival at one year, with secondary measures of delayed graft function in the first post operative week, graft function, primary non function and graft and patient survival at three months and one year. We are also recording the length of hospitalisation, and take biopsies for histology pre and post perfusion, plus biopsies of proven rejections.

 

The POMP trial is still recruiting in its 11 participating transplant centres and we aim to complete our recruitment target in early 2018.

COMPARE trial: oxygenated vs. non oxygenated hypothermic machine perfusion in kidney transplantation

 

This randomised controlled trial is designed to question whether oxygenated machine perfusion is superior to non-oxygenated machine perfusion in increasing the longevity and quality of older cardiac death donors (DCD) kidneys for transplant. The trial is led by Professor Jacques Pirenne and his team at the University Hospitals Leuven (BE) and includes transplant centres in Belgium, The Netherlands and the UK. The trial device is provided by Organ Assist Products B.V. and support has been given by the Centre for Evidence in Transplantation (University of Oxford, UK) in designing the study and writing the trial protocol.

 

The protocol sees DCD kidney pairs at donor centres immediately after procurement being randomised to hypothermic machine perfusion, one with oxygen, and one without oxygen. The organs are then transplanted into a recipient adult in end-stage renal failure on the active waiting list for a kidney only transplant. The primary outcome measure for this trial is long-term graft survival and secondary measures include primary non function, serum creanine at one, three and 12 months, functional delayed graft function as well as graft and patient survival.

 

The COMPARE trial has included a total of 105 transplanted kidney pairs and threfore reached its recruitment target in April 2017. The team is now busy collecting all patients' follow-up data until the last patient's 12 months appointment due in April 2018. Once the primary endpoints for the last patient is reached and the dataset is complete for the trial, data analysis will ensue with publications planned in late 2018 and 2019. More detailed sub-studies using the trial's sample collection will also be carried out beyond that timeframe.

This project has received funding from the European Union's 7th Framework Programme for research, technological development and demonstration under grant agreement 305934.

COPE Consortium - 2017