利福昔明和乳果糖预防肝硬化经颈静脉肝内门体分流术（TIPS）患者肝性脑病：一项多中心随机、双盲、安慰剂对照试验（PEARL 试验）。
Prevention of hepatic encephalopathy by administration of rifaximin and lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS): a multicentre randomised, double blind, placebo controlled trial (PEARL trial).
机构信息
Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
出版信息
BMJ Open Gastroenterol. 2020 Dec;7(1). doi: 10.1136/bmjgast-2020-000531.
INTRODUCTION
Cirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common (20%-54%) and often severe complication. A prophylactic strategy is lacking.
METHODS AND ANALYSIS
The Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a TIPS (PEARL) trial, is a multicentre randomised, double blind, placebo controlled trial. Patients undergoing covered TIPS placement are prescribed either rifaximin 550 mg two times per day and lactulose 25 mL two times per day (starting dose) or placebo 550 mg two times per day and lactulose 25 mL two times per day from 72 hours before and until 3 months after TIPS placement. Primary endpoint is the development of overt HE (OHE) within 3 months (according to West Haven criteria). Secondary endpoints include 90-day mortality; development of a second episode of OHE; time to development of episode(s) of OHE; development of minimal HE; molecular changes in peripheral and portal blood samples; quality of life and cost-effectiveness. The total sample size is 238 patients and recruitment period is 3 years in six hospitals in the Netherlands and one in Belgium.
ETHICS AND DISSEMINATION
This study protocol was approved in the Netherlands by the Medical Research Ethics Committee of the Academic Medical Centre, Amsterdam (2018-332), in Belgium by the Ethics Committee Research UZ/KU Leuven (S62577) and competent authorities. This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Study results will be submitted for publication in a peer-reviewed journal.
TRIAL REGISTRATION NUMBERS
ClinicalTrials.gov (NCT04073290) and EudraCT database (2018-004323-37).
简介
患有门静脉高压症的肝硬化患者可能会出现食管静脉曲张出血或难治性腹水，并可从经颈静脉肝内门体分流术（TIPS）中获益。TIPS 术后肝性脑病（HE）是一种常见（20%-54%）且通常严重的并发症。目前缺乏预防性策略。
方法与分析
在接受 TIPS 治疗的肝硬化患者中，通过给予利福昔明和乳果糖预防肝性脑病（PEARL）试验是一项多中心随机、双盲、安慰剂对照试验。接受 TIPS 治疗的患者被处方利福昔明 550mg，每日两次，乳果糖 25ml，每日两次（起始剂量）或安慰剂 550mg，每日两次，乳果糖 25ml，每日两次，从 TIPS 治疗前 72 小时开始至治疗后 3 个月。主要终点是 3 个月内出现显性 HE（OHE）（根据 West Haven 标准）。次要终点包括 90 天死亡率；第二发作 OHE 的发展；OHE 发作的时间；出现轻微 HE；外周和门静脉血样的分子变化；生活质量和成本效益。总样本量为 238 例患者，招募期为 3 年，在荷兰的 6 家医院和比利时的 1 家医院进行。
伦理与传播
本研究方案已在荷兰阿姆斯特丹学术医学中心的医学研究伦理委员会（2018-332）、比利时鲁汶大学医院伦理委员会（S62577）和主管当局批准。本研究将按照良好临床实践指南和《赫尔辛基宣言》的原则进行。研究结果将提交给同行评议的期刊发表。
试验注册号
ClinicalTrials.gov（NCT04073290）和 EudraCT 数据库（2018-004323-37）。
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