Randomized, Placebo-Controlled Trial of Transdermal Rivastigmine for the Treatment of Encephalopathy in Liver Cirrhosis (TREC Trial)  

作　　者：Patrick P. Basu Niraj James Shah Mark M. Aloysius Robert S. Brown 

机构地区：[1]Columbia University College of Physicians & Surgeons, New York, USA [2]James J. Peters VA Medical Center, New York, USA [3]King’s County Hospital, New York, USA

出　　处：《Open Journal of Gastroenterology》2014年第6期255-264,共10页肠胃病学期刊（英文）

摘　　要：Objectives: Cognitive dysfunction in patients with hepatic encephalopathy (HE) may be caused by alterations in cholinergic neurotransmission. The objective of the study was to evaluate the efficacy and safety of transdermal rivastigmine in improving cognitive function in patients with overt HE. Design: Randomized, controlled pilot study in which patients with grade 2 or 3 HE were treated with lactulose and randomized to receive either transdermal rivastigmine or placebo for 21 days. The modified encephalopathy scale (MES), object recognition test (ORT), trail test (TT), and serum ammonia were assessed at baseline weekly. Electroencephalography was performed at baseline and the final week of the study. Results: Patients were treated with lactulose (20 g/30 mL three times per day) and either transdermal rivastigmine (4.6 mg/d;n = 15) or placebo (n = 15). Transdermal rivastigmine significantly improved MES, ORT, and TT results compared with placebo (P ≤ 0.0001 at all 3 weeks for all 3 assessments). Serum ammonia improved in both treatment groups, although there was significantly greater improvement with placebo than rivastigmine after 2 weeks of treatment (P What is already known about this subject? ? Current approaches to the management of HE are primarily designed to reduce the levels of ammonia and other gut-derived toxins. ? Traditional strategies for HE treatment have included non-absorbable disaccharides (to decrease bowel transit time) or rifamixin (non-absorbable antibiotics to reduce ammoniogenic flora). ? No transdermal cholinomimetic agents have been used with oral lactulose to date, in HE. What are the new findings? ? Transdermal rivastigmine is safe for use in patients with grade 2 & 3 HE. ? Transdermal rivastigmine in combination with oral lactulose in this study is far superior to lactulose alone in improving cognitive function. How might it impact on clinical practice in the foreseeable future? ? Transdermal rivastigmine in combination with oral lactulose can be used safely in clinical practice. ? Objectives: Cognitive dysfunction in patients with hepatic encephalopathy (HE) may be caused by alterations in cholinergic neurotransmission. The objective of the study was to evaluate the efficacy and safety of transdermal rivastigmine in improving cognitive function in patients with overt HE. Design: Randomized, controlled pilot study in which patients with grade 2 or 3 HE were treated with lactulose and randomized to receive either transdermal rivastigmine or placebo for 21 days. The modified encephalopathy scale (MES), object recognition test (ORT), trail test (TT), and serum ammonia were assessed at baseline weekly. Electroencephalography was performed at baseline and the final week of the study. Results: Patients were treated with lactulose (20 g/30 mL three times per day) and either transdermal rivastigmine (4.6 mg/d;n = 15) or placebo (n = 15). Transdermal rivastigmine significantly improved MES, ORT, and TT results compared with placebo (P ≤ 0.0001 at all 3 weeks for all 3 assessments). Serum ammonia improved in both treatment groups, although there was significantly greater improvement with placebo than rivastigmine after 2 weeks of treatment (P What is already known about this subject? ? Current approaches to the management of HE are primarily designed to reduce the levels of ammonia and other gut-derived toxins. ? Traditional strategies for HE treatment have included non-absorbable disaccharides (to decrease bowel transit time) or rifamixin (non-absorbable antibiotics to reduce ammoniogenic flora). ? No transdermal cholinomimetic agents have been used with oral lactulose to date, in HE. What are the new findings? ? Transdermal rivastigmine is safe for use in patients with grade 2 & 3 HE. ? Transdermal rivastigmine in combination with oral lactulose in this study is far superior to lactulose alone in improving cognitive function. How might it impact on clinical practice in the foreseeable future? ? Transdermal rivastigmine in combination with oral lactulose can be used safely in clinical practice. ?

关 键 词：ACETYLCHOLINESTERASE CHOLINERGIC Function Hepatic ENCEPHALOPATHY RIVASTIGMINE 

分 类 号：R73[医药卫生—肿瘤]