VSL#3 and Spontaneous Bacterial Peritonitis

Ascites Clinical Trial

Official title:

The Effect of Probiotics on the Incidence of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis and Ascites

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01701297
• Other study ID #: 10GA021
• Secondary ID: 2010-022886-9210
• Status: Terminated
• Phase: Phase 2
• First received: August 8, 2012
• Last updated: October 27, 2016
• Start date: February 2012
• Est. completion date: October 2014

Study information

• Verified date: October 2016
• Source: Nottingham University Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Participant is willing and able to give informed consent for participation in the study.

• Male or Female, aged 18 years or above.

• Diagnosed with required disease/severity/symptoms as outlined in 6.3.1.

• Stable dose of current regular medication (e.g. diuretics, beta-blockers, vitamin supplementation) for at least 4 weeks prior to study entry.

• Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter

• Participants have clinically acceptable laboratory tests and ECG within 14 days of enrolment.

• Able (in the Investigators opinion) and willing to comply with all study requirements.

Willing to allow their General Practitioner and consultant

Exclusion criteria:

• Female participants who is pregnant, lactating or planning pregnancy during the course of the study.

• Presence of hepatocellular carcinoma

• Scheduled elective surgery or other procedures requiring general anaesthesia during the study.

• Participant who is terminally ill

• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

• Use of antibiotics or probiotics in the last 2 weeks

• Known hypersensitivity to trimethoprim, sulphonamides or any other ingredients in co-trimoxazole tablet.

• History of acute porphyria or serious haematological disorder.

• Participants who have participated in another research study involving an investigational product in the past 12 weeks

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ascites
• Decompensated Cirrhosis
• Fibrosis
• Liver Cirrhosis
• Peritonitis

Intervention

Drug:
• cotrimoxazole
Cotrimoxazole 960mg orally each day (two 480mg tablets)
• VSL#3 active
The prescribed dose was 2 sachets (containing 900 billion bacteria) orally each day for 48 weeks
• VSL#3 placebo
This was two placebo sachets identical to VSL#3 active sachet. The prescribed dose was 2 sachets orally each day for 48 weeks

Locations

Country	Name	City	State
United Kingdom	NUH NHS Trust	Nottingham	Nottinghamshire

Sponsors (2)

Lead Sponsor	Collaborator
Nottingham University Hospitals NHS Trust	VSL Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Liver-related mortality and liver related morbidity		12 months	Yes
Secondary	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	Yes