Intestinal Decontamination With Rifaximin. Effects on the Inflammatory and Circulatory State in Patients With Cirrhosis and Ascites - A Randomised Controlled Clinical Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Change from baseline in Hepatic venous pressure gradient (HVPG)
研究概览
简要总结
This investigational trial will be assessing the effect of rifaximin on pathophysiology and haemodynamics in the patient with liver cirrhosis, and addressing the effect of rifaximin on several organs on marker level. The molecular and physiological effects of rifaximin will be explored.
The investigators hypothesize that intestinal decontamination with rifaximin in patients with cirrhosis and ascites will interrupt bacterial translocation from the gut, diminish the following inflammatory response, prevent splanchnic vasodilatation and portal systemic contraction and thereby reduce the risk clinical complications to cirrhosis.
If rifaximin can correct small intestinal bacterial overgrowth and demonstrate improvement in liver haemodynamics, renal function and systemic dynamics, then these effects may contribute to the overall well-being of the patient and prevent complications to the underlying cirrhosis such as risk of infections, progression of disease, and admission to hospital.
详细描述
Background:
Ascites is a frequent complication of cirrhosis, occurring in 50% of patients and is associated with 50 % mortality in two years.
Bacterial infections in patients with cirrhosis are frequent during hospitalization and is an important precipitating event for the development of renal failure and hepatorenal syndrome, hepatic encephalopathy and possibly also variceal bleeding. High Child-Pugh Score, variceal bleeding and low ascitic fluid protein levels are associated with high risk of infection.
The infections are mainly triggered by gut bacterial translocation, the migration of microorganisms from the intestinal lumen to mesenteric lymph nodes or extra-intestinal sites. Some studies have shown derangements in the gut micro ecology of patients with liver cirrhosis, partly due to a decrease in small intestinal motility, which could cause small intestinal bacterial overgrowth. Combined with structural and functional alterations of the intestinal mucosa and deficiencies in defense mechanisms, this bacterial overgrowth contributes to bacterial translocation.
Circulating bacterial DNA is a marker of bacterial translocation that may enhance endothelial dysfunction and predict a poor outcome in cirrhosis and ascites. Selective gut decontamination prevents spontaneous bacterial infections and improves survival in advanced cirrhosis, such as in variceal bleeding and in patients with spontaneous bacterial peritonitis (SBP).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Decompensated liver cirrhosis and clinical signs of ascites
- •Age 18 - 80 years
- •Portal hypertension and hepatic venous pressure gradient (HVPG) of 10 mmHg or more
- •Women of child-bearing age must use safe anticonception, either hormonal anticonception or intrauterine device (IUD)
排除标准
- •Child-Pugh score above 12
- •Clinical signs of infection or biochemical signs of infection with leucocytes > 10x10'9/L and C-Reactive Protein (CRP)> 20 or positive urine culture
- •Hepatocellular carcinoma within the last year
- •Invasive cancer within the last five years
- •Hepatic encephalopathy above grade 1
- •serum creatinine > 200 micromoles/L
- •Transfusion requiring bleeding one week prior to inclusion
- •severe cardiac, pulmonary or kidney disease or IDDM
- •alcohol abuse and symptoms of abstinences
- •Expected survival less than 3 months
- •Denied consent
研究组 & 干预措施
Rifaximin
Rifaximin tablets for oral ingestion, 550 mg twice daily for 28 days.
干预措施: Rifaximin (Drug)
Placebo tablets
Placebo tablets similar in shape and size to intervention treatment, 1 tablet twice daily for 28 days.
干预措施: placebo (Drug)
结局指标
主要结局
Change from baseline in Hepatic venous pressure gradient (HVPG)
时间窗: 29 days
Evaluation of a change in HVPG where values at baseline are compared to values after treatment at 29 days.
次要结局
- Change from baseline in Glomerular filtration rate (GFR)(29 days)
研究者
Nina Kimer
MD, Phd-student
Copenhagen University Hospital, Hvidovre