Heidet Matthieu, Amathieu Roland, Audureau Etienne, Augusto Oriane, Nicolazo de Barmon Violaine, Rialland Amandine, Schmitz David, Pierrang François, Marty Jean, Chollet-Xémard Charlotte, Thirion Olivier, Jacob Line
Groupe Hospitalo-Universitaire Henri Mondor, SAMU 94, Assistance Publique - Hôpitaux de Paris, Créteil, France.
EA-4390 (Analysis of Risk in Complex Health Systems), Université Paris-Est Créteil, Créteil, France.
BMJ Open. 2018 Aug 10;8(8):e021943. doi: 10.1136/bmjopen-2018-021943.
The management of acute upper gastrointestinal bleeding (UGIB) is challenging in patients with cirrhosis, as it is responsible for severe complications and high mortality rates. Tranexamic acid (TXA) may help control the bleeding by counterbalancing cirrhosis-related hyperfibrinolysis. Still, there is a lack of unbiased data to conclude on its efficacy. The aim of this study is to evaluate the efficacy of TXA in the early treatment of acute UGIB in patients with cirrhosis.
This study is a multicentre, randomised, double-blind, placebo-controlled trial, for adult patients with cirrhosis presenting with an acute UGIB and allocated to one of two arms: TXA or placebo (saline). Physicians from emergency mobile services, emergency departments (EDs) or intensive care units (ICUs) can include patients. Besides study intervention, standard care for UGIB will be performed as recommended. Intervention will consist an intravenous infusion of 10 mL of TXA (1 g) or saline, immediately followed by three identical intravenous infusions over 8 hours each (total dose of 4 g of TXA or 40 mL of placebo over 24 hours). Main analyses will be conducted in intention to treat on every patient included, then in modified intention to treat on patients with underlying lesion of portal hypertension visualised by endoscopy. The main objective is to show efficacy of TXA until day 5 on a composite criterion (bleeding control, rebleeding episodes and mortality). Secondary objectives aim at showing the efficacy of TXA on each individual component of the main outcome measure and others at 6 weeks and later (transjugular intrahepatic portosystemic shunt procedure, cirrhosis-specific complications, length of stay in ICU and in hospital, safety and tolerance of TXA, liver transplantation). Included patients will be followed up to 1 year after inclusion.500 patients will be necessary to show a reduction in the prevalence of the primary outcome from 30% to 18% with a bilateral alpha risk of 5% and a power of 80%.
Ethical approval has been obtained from the Comité de Protection des Personnes Ile-de-France 1 (CPP-IDF1). Results will be disseminated via publications in peer-review medical journals and scientific forums.
This protocol is based on the latest version, as established on 11 October 2017 and validated by the IRB CPP Ile-de-France 1.
NCT03023189.
肝硬化患者急性上消化道出血（UGIB）的管理具有挑战性，因为它会导致严重并发症和高死亡率。氨甲环酸（TXA）可能通过平衡肝硬化相关的高纤维蛋白溶解来帮助控制出血。然而，目前缺乏公正的数据来确定其疗效。本研究的目的是评估TXA在肝硬化患者急性UGIB早期治疗中的疗效。
本研究是一项多中心、随机、双盲、安慰剂对照试验，针对患有急性UGIB的成年肝硬化患者，分为两组：TXA组或安慰剂组（生理盐水）。来自急救移动服务、急诊科（ED）或重症监护病房（ICU）的医生可以纳入患者。除研究干预外，将按照推荐进行UGIB的标准护理。干预措施包括静脉输注10毫升TXA（1克）或生理盐水，随后立即在8小时内进行三次相同的静脉输注（24小时内TXA总剂量为4克或安慰剂40毫升）。主要分析将在纳入的每例患者中按意向性治疗进行，然后在经内镜检查发现有门静脉高压基础病变的患者中按改良意向性治疗进行。主要目标是在第5天之前，根据综合标准（出血控制、再出血事件和死亡率）显示TXA的疗效。次要目标旨在显示TXA对主要结局指标的各个单独组成部分以及6周及以后的其他指标（经颈静脉肝内门体分流术、肝硬化特异性并发症、ICU和住院时间、TXA的安全性和耐受性、肝移植）的疗效。纳入的患者将在纳入后随访1年。需要500例患者才能显示主要结局的患病率从30%降至18%，双侧α风险为5%，检验效能为80%。
已获得法兰西岛大区第一保护人类委员会（CPP-IDF1）的伦理批准。结果将通过在同行评审医学期刊和科学论坛上发表进行传播。
本方案基于2017年10月11日确立的最新版本，并经IRB CPP法兰西岛大区第一批准有效。
NCT03023189。
