Granulocyte colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: a multicenter randomized trial (GRAFT-Trial)

粒细胞集落刺激因子（G-CSF）治疗慢加急性肝衰竭：一项多中心随机试验（GRAFT 试验）

• 批准号: 259386236
• 负责人: Professor Dr. Thomas Berg, since 1/2017
• 金额: --
• 依托单位: Klinik und Poliklinik für Gastroenterologie
• 依托单位国家: 德国
• 项目类别: Clinical Trials
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/259386236?language=en
• 关键词: Granulocyte; colony; stimulating; factor; CSF

The acute on chronic liver failure (ACLF) is characterised by a severe deterioration of liver function due to a precipitating event (e.g. variceal bleeding, infection, alcohol consumption, viral hepatitis or druginduced toxicity) on top of an underlying chronic liver disease. As therapeutic options are limited the mortality rate lies between 40 and 80% at 3 months. The granulocyte colony-stimulating factor (G-CSF) mobilized stem- as well as immune cells and improved liver function in preclinical trials. In two recent small randomized studies, G-CSF treatment reduced the rate of infectious complications and significantly improved patients´ survival in acute on chronic liver failure. Thus, G-CSF is a promising treatment option that needs to be evaluated in a multi-centre controlled trial. The GRAFT trial will randomise a total of 292 patients with acute on chronic liver failure from 20 German centres between standard of care with and without G-CSF. All participants will be followed for 12 months in order to evaluate safety and efficacy of G-CSF. If successful, the GRAFT trial has the potential to change clinical practice in acute on chronic liver failure.

慢性加急性肝衰竭（ACLF）的特征是在基础慢性肝病基础上，由于突发事件（例如静脉曲张出血、感染、饮酒、病毒性肝炎或药物诱导的毒性）导致肝功能严重恶化。由于治疗选择有限，3个月时的死亡率为40%至80%。粒细胞集落刺激因子（G-CSF）动员干细胞和免疫细胞，并在临床前试验中改善肝功能。在最近的两项小型随机研究中，G-CSF治疗降低了感染并发症的发生率，并显着改善了慢性肝衰竭急性患者的生存率。因此，G-CSF是一种有前途的治疗选择，需要在多中心对照试验中进行评估。GRAFT试验将从20家德国中心随机选择292例慢性肝衰竭急性发作患者，接受标准治疗加和不加G-CSF治疗。所有受试者将接受12个月的随访，以评估G-CSF的安全性和疗效。如果成功，GRAFT试验有可能改变慢性肝衰竭急性发作的临床实践。