Humphries Christopher, Addison Melisande, Aithal Guruprasad, Boyd Julia, Briody Lesley, Campbell John D M, Candela Maria Elena, Clarke Ellise, Coulson James, Downing-James Nicholas, Fontana Robert John, Geddes Ailsa, Grahamslaw Julia, Grant Alison, Heye Anna, Hutchinson James A, Jones Ashley, Mitchell Fiona, Moore Joanna, Riddell Alice, Rodriguez Aryelly, Thomas Angela, Tucker Garry, Walker Kim, Weir Christopher J, Woods Rachel, Zahra Sharon, Forbes Stuart J, Dear James W
Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, UK.
Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, UK.
BMJ Open. 2024 Dec 9;14(12):e089417. doi: 10.1136/bmjopen-2024-089417.
Acute liver failure (ALF) has no effective treatment other than liver transplantation and is commonly caused by paracetamol overdose. New treatments are needed to treat and prevent ALF. Alternatively-activated macrophages (AAMs) can promote resolution of liver necrosis and stimulate hepatocyte proliferation. Using AAMs in unscheduled care requires the use of an allogeneic product. A clinical trial is needed to determine the safety and tolerability of allogeneic AAMs.
A single-centre, open-label, dose-escalation, phase 1 randomised trial to determine whether there is dose-limiting toxicity of AAMs in patients with paracetamol-induced acute liver injury. Randomisation will occur at higher doses. Between 17 and 30 patients will receive treatment, subject to dose-limiting toxicity and an adaptive trial design which aims to reduce the risk of allocation bias through blinding and randomisation.
The trial will be conducted according to the ethical principles of the Declaration of Helsinki 2013 and has been approved by North East-York Research Ethics Committee (reference 23/NE/0019), National Health Service Lothian Research and Development department, and the UK Medicines and Healthcare products Regulatory Agency. When the trial concludes, results will be shared by presentation and publication.
ISRCTN12637839.
除肝移植外，急性肝衰竭（ALF）尚无有效治疗方法，且通常由对乙酰氨基酚过量引起。需要新的治疗方法来治疗和预防ALF。替代性活化巨噬细胞（AAM）可促进肝坏死的消退并刺激肝细胞增殖。在非计划性治疗中使用AAM需要使用同种异体产品。需要进行一项临床试验来确定同种异体AAM的安全性和耐受性。
一项单中心、开放标签、剂量递增的1期随机试验，以确定AAM对乙酰氨基酚诱导的急性肝损伤患者是否存在剂量限制性毒性。将在较高剂量下进行随机分组。17至30名患者将接受治疗，具体取决于剂量限制性毒性和适应性试验设计，该设计旨在通过盲法和随机化降低分配偏倚的风险。
该试验将根据2013年《赫尔辛基宣言》的伦理原则进行，并已获得东北约克研究伦理委员会（参考号23/NE/0019）、国民保健服务洛锡安研发部和英国药品和医疗产品监管局的批准。试验结束时，将通过报告和发表分享结果。
ISRCTN12637839。
