UK launches world’s largest ever randomised controlled trial in organ donation
The world’s biggest donor intervention study has been launched in the UK to look at improving the quality of donated organs.
The SIGNET study (Statins for Improving orGaN outcomE in Transplantation) will be the largest ever global single, blind randomised controlled trial in organ donation.
It will look to recruit 2,600 patients after the diagnosis of death by neurological criteria (DBD) in 79 hospital Trusts across the UK over 4 years.
It’s hoped that in the long-term evidence will show that statins will reduce inflammation and improve organ quality and therefore the drug can be used safely as a standard part of care for organ donors.
Statins are widely used as cholesterol lowering agents but may have other benefits many of which revolve around reducing 'inflammation', which is often the root cause of damage to organs in both a donor and a recipient. A single dose of simvastatin will be given after consent from the donor’s family.
Around 75% of hearts offered for transplant are not used due to damage or poor function – which is the most common cause of death for the recipient post-transplant. So often surgeons must decide whether or not to accept the organ based on the potential outcome for their patient.
Any step in the intervention of the donor which might improve the transplanted heart could have a major benefit to the recipient outcome and increase the number of hearts viable for transplant.
Former heart and lung surgeon, Professor John Dark, is one of the lead investigators into the study. He is currently the Professor of Cardiothoracic Surgery at Newcastle University, who applied for the grant to fund the study.
He said: "We expect better quality organs to come from donors who have been treated with simvastatin. A previous smaller study in Finland (1) has shown that this was clearly the case for the heart and hinted at improvements in quality for lungs and liver also.
"Interestingly, in lung donation the recipients who got organs from donors treated with simvastatin showed half the level of primary graft dysfunction, which measures organ damage.
"What we hope to do in the future is to make statins part of the standard treatment for organ donors and then explore other drugs that may continue to improve the condition of donated organs.”
The study is being funded by a research grant from the National Institute for Health Research (NIHR) Health Technology Assessment Programme following an application from Newcastle University.
The NIHR has given £1.3 million to fund the study and it will be run by NHS Blood and Transplant’s Clinical Trials Unit in Cambridge, with Newcastle Upon Tyne Hospitals NHS Foundation Trust being the sponsors.
Dr Dan Harvey is the National Lead for Innovation & Research in Organ Donation at NHS Blood and Transplant and is the co-lead investigator on the SIGNET study.
He said: “We have never done a major randomised trial across so many donor hospitals and involving so many donors and recipients previously, and the fact that we are working so closely with our colleagues at Newcastle University, Newcastle Upon Tyne Hospitals NHS Foundation Trust, the NIHR and all the donor hospitals taking part in the trial, shows how uniquely well set up the UK is for delivering this kind of research.
"It’s really exciting to be involved in leading such a study because we’d really like the UK organ donation and transplant community to become the world leaders in research.”
In the trial, half the consented donors will receive the drug in addition to their standard donor care. The drug is given through a tube running into the stomach, which will already be present in most donors.
The drug will be given as soon as the family have consented to both organ donation and involvement of their loved one in this research.
Half of all the recipients will then receive an organ from a donor given the drug. The results of all the transplants will be followed up, comparing what happens in those who received the drug treated organs, and those who did not.
Professor John Dark continued: “We are in a unique position in the UK to have organ donation and transplantation under one roof with NHS Blood and Transplant co-ordinating the whole process from donor to recipient.
"The UK is also unique in having the centralised Transplant Registry which gathers information of all recipient outcomes and follows their progress post-transplant.
"The fact that all of this is all done within the NHS puts the UK in a unique position. Only by doing studies like this do we move our knowledge forward and we’d certainly like to do more of this kind of intervention research in the future.”
NHS Blood and Transplant will help to deliver the study through the expert specialist nurses in organ donation (SNODs) that support families giving consent to organ donation in hospitals, and the national logistical and coordination teams who facilitate the transplants.
Dr Dan Harvey continued: “The importance of the specialist nurses in organ donation can’t be underestimated. They do an incredible job in supporting families at one of the hardest times in their lives during the process of organ donation.
"Research is an important choice for donor families which might improve the quality of the donation, and family understanding, and support are crucial in the success of the trial.”
Professor Paul Dark, NIHR's National Specialty Lead for Critical Care, said: "This is the world's largest study to investigate whether Simvastatin, a safe and commonly used drug, can help improve the quality of donated organs.
"Previous studies have shown statins can reduce inflammation and improve organ quality. This new study involving giving organ donors Simvastatin, in addition to the standard donor care, is critical research which we hope will show major benefits to the recipient donor.
"Clinical trials such as this one are vital to helping us reveal new evidence and answer important health questions."
Recruitment for the trial will be continuous over 48 months, followed by a 12 month follow up period for collection of data on all primary and secondary outcomes on transplanted organs. Final analysis and preparation of the final report will be completed by July 2026.
Eligibility criteria for taking part in the trial
- Patients confirmed dead using neurological criteria
- Consent for organ donation in place, as defined by the Human Tissue Act and accompanying legislation and Codes of Practice
- Within a recruiting Intensive Care unit
Exclusions:
- Aged under 18
- Refusal of consent from donor family
- Planned donation after cessation of circulation (DCD)
- Known hypersensitivity to Simvastatin