Clinical Trials Unit, NHS Blood and Transplant, Cambridge, UK.
Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK
BMJ Open. 2024 Sep 18;14(9):e086352. doi: 10.1136/bmjopen-2024-086352.
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.
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.
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.
ISRCTN11440354.
在终末期器官衰竭的患者中成功进行器官移植可以提高长期生存率、改善生活质量并降低国民保健服务的成本。尽管在过去十年中，已故器官捐献者的数量有所增加，但可供移植的合适器官仍然严重短缺。英国超过一半的捐献者在脑干受压后通过神经学标准被确认为脑死亡，这导致捐献者遭受严重的生理压力，同时伴有过度炎症状态。脑干死亡相关的功能障碍是导致器官功能不良和利用率低下的重要原因。例如，超过 30%的脑死亡后心脏移植受者需要短期机械心脏支持，这反映了供体心脏功能障碍。先前的一项小型随机研究表明，如果给予供体辛伐他汀，心脏移植受者的结局会有所改善。SIGNET 从该研究中获得灵感，并假设在诊断脑死亡后至器官获取前的时间段内，给予辛伐他汀可减少供体心脏和其他器官的损伤。
SIGNET 是一项多中心、单盲、前瞻性、分组序贯、随机对照试验，旨在评估对通过神经学标准诊断为脑死亡的潜在器官捐献者给予单次大剂量辛伐他汀对所有器官受者结局的影响。该试验将在英国至少 89 个地点进行，目标是在 4 年内招募 2600 名供者。
SIGNET 获得了伦敦皇后广场研究伦理委员会的有利意见（Ref：21/LO/0412），并在 2023 年 1 月批准了第 1 次重大修正案后，当前方案为第 2 版（2022 年 12 月 7 日）。第 1 次重大修正案澄清了同意程序，并增加了额外的地点和处方医师。该研究的结果将公开，并通过在同行评议期刊上发表论文和在国内外平台上发表会议报告在本地和国际上进行传播。
ISRCTN83254437。
