VSL#3 and Spontaneous Bacterial Peritonitis

Phase 2

Terminated

• Conditions: Ascites; Decompensated Cirrhosis
• Interventions: Drug: cotrimoxazole; Drug: VSL#3 placebo; Drug: VSL#3 active

• Registration Number: NCT01701297
• Lead Sponsor: Nottingham University Hospitals NHS Trust

Brief Summary

Research question: Do oral probiotics in patients with cirrhosis and ascites reduce intestinal bacterial concentrations, ascitic bacterial DNA, SBP and bacteraemia compared to antibiotics or placebo?

This study is designed to investigate the effects of an oral probiotic (VSL#3; a mixture of "healthy" bacteria for the intestines) compared to an antibiotic or placebo in preventing infection developing in the abdominal fluid ("ascites") that collects in patients with advanced liver disease ("cirrhosis"). Patients already having had infection will be excluded from the study. Clear inclusion and exclusion criteria will be met and patients will be monitored throughout the study to examine whether they have required more hospitalisations, their rate infection in abdominal fluid or elsewhere and the level of liver function.

Detailed Description

The prevalence of cirrhosis is increasing in the UK. Decompensation heralds a poor outcome, with mortality in those developing ascites approximately 50% over the following 1-2 years. Spontaneous bacterial peritonitis (SBP) in ascitic fluid further reduces survival and occurs due to a combination of increased intestinal epithelial dysfunction, bacterial translocation to mesenteric lymph nodes and ascitic fluid, and reduced opsonisation and neutrophil function. Even with antibiotic treatment, 3-month mortality from SBP is approximately 40% and results in expensive in-patient care. Several studies have confirmed the benefit of secondary prophylaxis with long-term oral antibiotics in patients with advanced liver disease (e.g. norfloxacin, co-trimoxazole) and others suggest that in patients at high risk of developing SBP, primary antibiotic prophylaxis improves rates of sepsis and survival. Problems with these strategies include emergence of bacterial resistance, and development of antibiotic-associated diarrhoea (including C. difficile infection, which has a high case-fatality rate in those with cirrhosis). Local bacterial resistance profiles and association with C. difficile infection favour the choice of co-trimoxazole in our study population. Patients with advanced cirrhosis taking co-trimoxazole have previously demonstrated reduced liver-related outcomes such as infection and death3. Probiotic preparations alter intestinal bacterial flora and improve intestinal barrier and neutrophil function. Faecal bacterial counts of E. coli and Streptococcus (organisms commonly responsible for SBP) showed a 2-log fall with probiotics, although whether they could reduce the incidence of SBP remains unexamined.

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-08-08
• Study First Submitted QC: 2012-10-04
• Study First Posted: 2012-10-05
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-27
• Last Update Posted: 2016-10-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Co-trimoxazole	cotrimoxazole	Co-trimoxazole 960mg daily po
VSL#3 placebo	VSL#3 placebo	VSL#3 placebo 2 sachets/daily
VSL#3 active	VSL#3 active	VSL#3 active 2 sachets/daily

Primary Outcome Measures

Name	Time	Method
Liver-related mortality and liver related morbidity	12 months

Secondary Outcome Measures

Name	Time	Method
Incidence of SBP, variceal bleeding, any non-SBP sepsis (e.g. pneumonia, urinary tract infection), clinical episodes of encephalopathy and the incidence of C. difficile infection.	12 months

Trial Locations

Locations (1)

NUH NHS Trust; 🇬🇧 Nottingham, Nottinghamshire, United Kingdom