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Introduction Successful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased organ donors over the last decade, there remains a considerable shortfall of suitable organs available for transplantation. Over half of UK donors are certified dead by neurological criteria following brain stem compression, which leads to severe physiological stress in the donor, combined with a hyperinflammatory state. Brain stem death-related dysfunction is an important reason for poor organ function and hence utilisation. For example, more than 30% of donation after brain stem death cardiac transplant recipients need short-term mechanical cardiac support, reflecting donor heart dysfunction.A small, randomised study previously showed improved outcomes for cardiac transplant recipients if the donor was given simvastatin. SIGNET takes inspiration from that study and hypothesises a potential reduction in damage to the heart and other organs during the period after diagnosis of death and prior to organ retrieval in donors that receive simvastatin.Methods and analysis SIGNET is a multicentre, single-blind, prospective, group sequential, randomised controlled trial to evaluate the benefits of a single high dose of simvastatin given to potential organ donors diagnosed dead by neurological criteria on outcomes in all organ recipients. The trial will run across a minimum of 89 UK sites with a recruitment target of 2600 donors over 4 years.Ethics and dissemination SIGNET received a favourable opinion from the London, Queen Square Research Ethics Committee (Ref: 21/LO/0412) and following approval of substantial amendment 1 in January 2023, the current protocol is version 2 (7 December 2022). Substantial amendment 1 clarified consent procedures and added additional sites and prescribers. Findings from the study will be publicly available and disseminated locally and internationally through manuscript publications in peer-reviewed journals and conference presentations at national and international platforms.Trial registration number ISRCTN11440354

Background: Over 40% of deceased donors in the UK donate after circulatory death (DCD). Normothermic regional perfusion has been reported to improve outcomes in such donors in Europe and the United States. Unlike the United States, legal and professional requirements in the UK prevent cannulation and heparinization before verification of death, which must be a minimum of 5 min after circulatory arrest. We developed a novel protocol for in situ normothermic regional perfusion (NRP) which complied with these requirements., Methods: NRP was achieved by cannulating the aorta and vena cava after death. Donor blood was then warmed and oxygenated using a bespoke extracorporeal membrane oxygenator circuit before return to the donor. A shunt was incorporated into the extracorporeal circuit to permit heparin mixing before oxygenation and warming was commenced to prevent thrombosis of the oxygenator. Normothermic perfusion was continued for 2 hr before in situ cold perfusion with preservation fluid. All organs were subject to static cold storage after recovery., Results: Eight controlled DCD donors underwent NRP from which 3 livers, 2 pancreases, and 14 kidneys were transplanted. Four livers were not used because of biochemical evidence of hepatocellular damage and one because of cirrhosis. Two kidneys were lost from venous thrombosis before function returned and two developed delayed graft function; all transplanted livers and pancreases had primary function., Conclusions: Cannulation and heparinization after circulatory arrest does not prevent successful normothermic regional perfusion. The technique permits evaluation of donor organs before implantation and may improve short-term outcomes.