RIFSYS
Research type
Research Study
Full title
A placebo controlled single centre double blind randomised trial to investigate the efficacy of Rifaximin versus placebo in improving systemic inflammation and neutrophil malfunction in patients with cirrhosis and chronic hepatic encephalopathy
IRAS ID
144665
Contact name
Julia Wendon
Contact email
Sponsor organisation
King's College London
Eudract number
2013-004708-20
Clinicaltrials.gov Identifier
Research summary
Patients with liver disease resulting in cirrhosis are prone to infection which is frequently a precipitant of hepatic encephalopathy, a constellation of symptoms affecting brain function which at worst can cause coma. Bacterial infections are of particular concern in patients with cirrhosis because they are poorly tolerated. Severe infection (’sepsis’) occurs in approximately 40% of patients with cirrhosis and is a major cause of death.
Bacteria leaking from the gut into the bloodstream causes an inflammatory response within the liver, which is one of the major organs that removes bacteria and their toxins (’endotoxins’) from the bloodstream. Several mechanisms have been proposed in this process which depends upon a balance between the barrier functions of the gut and the ‘detoxifying’ capacity of the liver. Those with established liver cirrhosis have been shown to have escape of endotoxin into the bloodstream produced by bacteria that reside in their intestines, which becomes more permeable or ’leaky’.
Gut dysfunction is defined by changes in the types of bacteria within the bowel and in overall leakiness (’permeability’) allowing bacterial products which would otherwise be contained within the gut to travel into the bloodstream and lymphatic system with detrimental effects elsewhere in the body. This passage of bacterial products is termed bacterial translocation, and their effects on the liver and general immune system can be then be measured.
Susceptibility to infection and may also have a more direct role in hepatic encephalopathy. A therapeutic strategy utilising Rifaximin - a non-absorbable antibiotic - to modulate gut bacteria could potentially lower gut-derived systemic inflammation, harmful endotoxin exposure and infection in this population improving outcomes and prolonging transplant-free survival.
Positive results from this study would support further studies investigating potential benefits of using Rifaximin to improve immune function, as well as reduce the recurrence of hepatic encephalopathy, in patients with cirrhosis.
REC name
South Central - Oxford C Research Ethics Committee
REC reference
14/SC/0088
Date of REC Opinion
14 Mar 2014
REC opinion
Further Information Favourable Opinion