Impact case study database

Liver transplantation is a highly effective treatment for end-stage liver failure, but is heavily constrained by the limited pool of donor organs. In the UK in the year to March 2018, there were 1,574 deceased donors, 1,149 liver retrievals and 975 liver transplants, indicating 62% overall liver utilisation. The highest-risk donor organs, including from donors after circulatory death rather than donors after brain death, were particularly poorly utilised (34%). As a result of this under-utilisation, in 2018 some 30% of listed patients were still waiting for a transplant for six months after listing, and 12% of listed patients died whilst still on the waiting list within two years [A] .

The research undertaken by Friend demonstrated the potential to increase the number of livers available for transplantation through increased utilisation of donor livers by warm perfusion, and the collaboration with Coussios made this technically possible through the development of the OrganOx metra. The first patient to benefit from this new approach was successfully transplanted in February 2013, and following successful completion of this Phase I study [5] the OrganOx metra received its CE mark as a medical device in 2016. Based on evidence from [6], machine perfusion was endorsed by NICE in January 2019 [B]. By December 2020, the OrganOx metra was being used routinely across all seven UK transplant centres in the UK (Birmingham, Cambridge, King’s, Leeds, Edinburgh, Royal Free and Newcastle). It total it has been used to enable over 850 liver transplants in 4 continents and 13 countries (UK, Austria, Italy, Spain, Germany, Belgium, France, the Netherlands, India, UAE, Australia, Canada, and USA) [C].

The OrganOx metra has significant benefits for both liver transplant recipients and patients with end stage liver disease who are awaiting a liver transplant. Improved patient outcomes are due to a reduction in damage to the perfused liver after it has been removed from the donor, and the ability to assess the donated liver’s function before it is transplanted, which result in more livers available for transplantation by using organs which would previously have been discarded. By increasing how long the liver can be stored before a transplant, clinicians can also choose to undertake a transplant at the optimal time point.

In the large randomised trial [6], the Oxford team halved the organ discard rate from 24% to 12%. Even though more organs (including more marginal organs) were utilised and were preserved for 50% longer, the post-transplant outcomes were still significantly better for normothermically preserved organs, as evidenced by a 50% decrease in post-transplant graft injury. The Professor of Transplantation at Addenbrooke’s Hospital, Cambridge, the first UK centre to fully adopt the OrganOx metra for routine clinical use, confirmed in October 2020:

“Since its introduction into our routine clinical practice in February 2018 we have increasingly used the machine in three settings, to assess donor livers where doubt existed over viability, to enable us to tackle difficult recipient procedures without the pressure of accumulating cold ischaemia, and to overcome logistical issues such as where we accepted two livers simultaneously. By far the biggest use (70%) has been in the assessment of donor livers. Since we started using the normothermic liver perfusion our transplant activity has increased around 30%...As you would imagine this has had an impact on our waiting times and waiting list mortality, as well as enabling us to successfully use livers that would otherwise not have been used by any centre in the UK.” [D]

NICE issued a press release in January 2019 announcing their recommendation of the procedure and highlighting the benefits to patients:

“Every year hundreds of people with advanced liver disease die whilst waiting for a transplant. This new device offers real hope as it may improve transplant outcomes and allow livers that were previously thought to be unsuitable to be used and also increase the time that livers are able to be kept. It is an exciting development that has the potential to shorten waiting list times and reduce mortality rates from advanced liver disease. After transplant, the vast majority of people go on to lead full and healthy lives and it is truly amazing to see the transformation.” Director of Policy at the British Liver Trust [E].

In addition to increasing donated organ utilisation, the introduction of the OrganOx metra in to the seven UK transplant centres has had a significant impact on clinical practice in the field of liver transplantation. An independent study (VITTAL: Viability Testing and Transplantation of Marginal Livers, NCT02740608), led by the University of Birmingham between November 2016 – February 2018, investigated the impact of normothermic machine perfusion on utilisation of liver grafts that had been discarded by all seven liver transplant centres in the UK. Of the 31 liver grafts perfused on the OrganOx metra, 22 were subsequently transplanted with 100% 90-day survival, demonstrating that normothermic machine perfusion can enable safe utilisation of over 70% of presently discarded grafts [F]. Chief Investigator of the VITTAL study, transplant surgeon at University Hospital's Birmingham NHS Foundation Trust, said:

“In the 30 years I've been involved with transplantation, there have been three or four events which have been game changers and I'm absolutely certain we are looking at a game changer that will change the way we practice organ storage and transplantation. It is already changing practice at the centres that have been able to use this technology either within clinical trials or within an expansion of service evaluation” [E].

The OrganOx metra has also had a significant impact on transplantation logistics. By increasing preservation times from the conventional maximum of 12 hours to well over 30 hours [G], clinicians have more flexibility about the timing of surgery and are able to plan more transplants as day cases, as noted in [6]. A study on the introduction of normothermic machine perfusion (NMP) at the Medical University of Innsbruck, Austria, found that “NMP in a multidisciplinary approach enables a safe prolongation of liver preservation and overnight organ care. A first field test of NMP indicates safety and benefit of this approach” [G]. This experience led to the omission of night-time procedures and parallel transplantations in Innsbruck [G]. In a separate study, use of the OrganOx metra device allowed 84% of transplants to take place during the day versus 65% with static cold storage [H]. This may help transplant surgical teams avoid ‘burn-out’ of key personnel. There is good evidence that daytime operations also have better outcomes for patients; for example, Yang et al [I] found that after-hours surgery was associated with significantly increased postoperative mortality and morbidity, and that: “ The timing of surgery plays a role in the outcome after the procedure and that both mortality and morbidities increase in surgeries performed outside of the regular working hours”.

A UK health economic study conducted by the University of Southampton in 2019 [J] concluded that, even though normothermic machine perfusion is more costly than static cold storage, it is also significantly more cost-effective by virtue of enabling additional transplants, with patients experiencing lower rates of early allograft dysfunction and adverse events: its incremental cost-effectiveness ratio was found to be GBP7,876 per Quality-Adjusted Life Year (QALY) gained.

In the first three years since CE marking in 2016, the OrganOx metra has seen over GBP7,000,000 of cumulative direct sales since product CE marking in 2016. As of October 2020, the company employs 29 staff (headcount): 23 in the UK, 4 in the US, 1 based in France and 1 based in Germany. Revenue for the period 1st May 2019 – 30th April 2020 was GBP2,200,000 which represents a 30% increase in revenue from the previous year [ C]. 40 devices are in use worldwide across Europe, North America, Asia and Australia. In January 2020, the company received a GBP4,600,000 investment from BGF, a UK investment company, to enable expansion in the US, where a subsidiary has been incorporated [C].

The OrganOx metra was recognised in the 2013 IET Innovation Awards, receiving 1^st prize in 3 of 15 categories, including: ‘Best Healthcare Technology’, ‘Best Intelligent System’ and ‘Best Emerging Technology Design’. The OrganOx metra was further shortlisted as one of 4 finalists for the 2019 50^th anniversary MacRobert award of the Royal Academy of Engineering. In September 2019, OrganOx won the ‘Best Proof-of-Value of an Innovation’ category at the US Medtech Insight Awards in Boston, attracting the following citation:

“This is a major advancement in organ preservation. There is well-documented unmet medical need in this area, and it is a true achievement to have a method to help secure desperately needed organs for patients. The judges commented that OrganOx represents the true aspects of what it takes to be best value and best for patients. The need for better preservation for transported organs has been a true roadblock for patients desperately waiting for organ transplants. The perseverance of the team is obvious, and they overcame huge roadblocks to achieve success.” [K].