Statins for Improving orGaN outcomE in Transplantation (SIGNET)

Summary of Research (abstract) Design: This is a multi-centre, single-blind prospective, group sequential, randomised controlled trial. Randomisation will be in a 1:1 ratio and will be stratified according to whether the donor was receiving statin therapy at ICU admission. Randomisation will not be stratified by transplanting centre (unknown at the time) or donation hospital (standard donor management applies at all hospitals and there is no evidence that donor hospital influences recipient outcomes). Setting: This study will be undertaken at up to 80 major donation hospitals (defined as > 6 organ donors per year) and will capitalise on infrastructure unique to the UK to deliver cost effective research in organ donation. We have a robust network of Clinical Leads for Organ Donation (intensivists at hospitals with high donor numbers), a cohort of Specialist Nurses in Organ Donation (SNODs) who have extensive training in discussing consent with donor families under the most distressing of circumstances, a national organ matching service and a national transplant registry which includes detailed recipient outcomes (UK Transplant Registry). After approach for consent for organ donation, research consent from donor families will be requested by the SNOD, who will subsequently manage the online randomization system established by the clinical trials unit. Population: Adult, brain-stem dead donors at major organ donation centres in the UK Intervention: A single dose of 80mg Simvastatin, given via nasogastric tube (already in place in >80% of donors) will be given as soon as possible after obtaining consent from the donor family Control group treatment: The standard donor management protocol, will ensure that treatment will be similar in all respects other than the intervention. Outcomes: The Primary Outcome will be a composite of mortality, cardiac mechanical support or renal replacement therapy within 30 days following heart transplant. Secondary outcomes are important clinical and safety organ specific transplant outcomes routinely collected by the UK Transplant Registry for all solid organs transplanted from donors in the study. Follow up: 30 days, 3 months and up to 1-year post transplant Sample size: 1300 per group, 2600 patients in total. Project time frames:Study set up will require 6 months, followed by a recruitment phase of 48 months, with an additional 15 months for follow up and close out.The total project duration is 69 months. Randomisation of donors at designated donation hospitals will begin in April 2021. Analysis of consent and inclusion will be continuous, with review at the end of year 1. Recruitment will be monitored on a monthly basis by the Trial Management Group, with planned interim analysis at two and three years for harm, benefit and futility.Recruitment will run for a total of 48 months, followed by a 12 month follow up period for collection of all organ primary and secondary outcomes. Final analyses and preparation of the final report will be completed by the end of the contractual period (June 2026).