Effect of Administration "Add on" of Rifaximin on Portal Hypertension of Patients With Liver Cirrhosis and Esophageal Varices in Standard Therapy With Propranolol
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change of Hepatic Venous Pressure Gradient
研究概览
简要总结
The purpose of this study is to assess whether the add of Rifaximin in patients with liver cirrhosis and esophageal varices treated with a standard therapy with beta blockers, leads to a significant reduction of portal hypertension.
详细描述
It is well recognized that the gut flora may play an important role in the development of complications of liver cirrhosis, such as hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP) and variceal bleeding, which are are directly caused or aggravated by the translocation of enteric bacteria or their products into the blood of cirrhotic patients.Preliminary studies have shown that selective intestinal decontamination appears to ameliorate the hyperdynamic circulatory state of cirrhosis. The investigators hypothesize that a modulation of gut microbiota by administering a non-adsorbable antibiotic, in addition to beta-blockers, can be a safe strategy to reduce the portal pressure, influencing favorably hemodynamics of portal circulation. Thus, the purpose of this study is to evaluate if in patients with liver cirrhosis and esophageal varices at high risk of bleeding, Rifaximin, administered in addition to standard therapy with beta - blockers (propranolol), for a time of 60 days: leads to a significant reduction of Hepatic Venous Pressure Gradient (it will be assessed by hepatic vein catheterization), 2) modify the intestinal flora in favor of specific families of bacteria (it will be assessed by fecal microbiota analysis), 3) change systemic inflammatory responses (it will be assessed by serum pro-inflammatory cytokines) 4) change in cognitive functions (it will be assessed by neuropsychological and electroencephalogram evaluations).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of liver cirrhosis (based on clinical, biochemical and radiological criteria with or without liver biopsy)
- •Presence of esophageal varices at high risk of bleeding
- •Hepatic Venous Pressure Gradient > 12 mmHg.
- •19≤ age ≤75
- •Informed Consent
排除标准
- •Patients already treated with beta blockers
- •Treatment with systemic antibiotics and/or non-absorbable intestinal antibiotics in the previous two weeks
- •Bacterial infection, spontaneous bacterial peritonitis
- •overt hepatic encephalopathy in the last week
- •active gastrointestinal bleeding, or in the last week
- •active alcoholism or drug abuse in last 3 weeks
- •Acute Alcoholic Hepatitis
- •Hepatocellular carcinoma or other neoplasm
- •significant coronary artery disease (angina NYHA III/IV), congestive heart failure (NYHA III/IV), relevant cardiomyopathy, history of myocardial infarct within the last 12 months
- •Contraindications to the administration of beta blockers; allergy to Rifaximin
- •Pregnancy or breastfeeding
- •Refusal to participate
研究组 & 干预措施
Rifaximin
Rifaximin 550 mg 1 tablet BID for 60 days
干预措施: Rifaximin (Drug)
Placebo
Placebo 1 tablet BID for +60 days
干预措施: Placebo (Drug)
结局指标
主要结局
Change of Hepatic Venous Pressure Gradient
时间窗: Time 0 and after 60 days
At Time 0 and after 60 days all patients will underwent hepatic vein catheterization to obtain the Hepatic Venous Pressure Gradient. Treatment response is defined as a decrease from baseline in the hepatic venous pressure gradient of at least 20% or less than 12 mmHg
次要结局
- Change of cognitive function(Time 0 and after 60 days)
- Modification of fecal bacteria(Time 0 and after 60 days)
- Change of systemic inflammatory response(Time 0 and after 60 days)
研究者
Piero Amodio
Professor
University of Padova