UK launches world’s largest ever randomised controlled trial in organ donation
The world’s biggest trial 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), funded by the NIHR, 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.
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."
Professor John Dark, one of the lead investigators into the study, said: “We expect better quality organs to come from donors who have been treated with simvastatin. A previous smaller study in Finland* 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 funded by NIHR’s Health Technology Assessment (HTA) Programme following an application from Newcastle University. 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.
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.
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.