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Lookup NU author(s): Phil Mawson, Dr Guy MacGowanORCiD, Professor Neil SheerinORCiD, Professor Andrew FisherORCiD, Professor James Shaw, Professor John Dark
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. 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.
Author(s): Evans A, Mawson P, Thomas H, Keen K, Watson CJ, McAuley DF, MacGowan GA, Sheerin NS, Fisher A, Shaw J, Yates H, Fallow A, Kounali D, Banks J, Stevens M, Paul R, Hodge R, Lawson E, Harvey D, Dark J
Publication type: Article
Publication status: Published
Journal: BMJ Open
Year: 2024
Volume: 14
Issue: 9
Online publication date: 18/09/2024
Acceptance date: 19/08/2024
Date deposited: 19/08/2024
ISSN (print): 2044-6055
ISSN (electronic): 2044-6055
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/bmjopen-2024-086352
DOI: 10.1136/bmjopen-2024-086352
PubMed id: 39299790
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