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VSL#3 and Spontaneous Bacterial Peritonitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01701297
Recruitment Status : Terminated (Unable to obtain QP release certification from the manufacturer (VSL3) for shipment of IMP)
First Posted : October 5, 2012
Last Update Posted : October 28, 2016
VSL Pharmaceuticals
Information provided by (Responsible Party):
Nottingham University Hospitals NHS Trust

Tracking Information
First Submitted Date  ICMJE August 8, 2012
First Posted Date  ICMJE October 5, 2012
Last Update Posted Date October 28, 2016
Study Start Date  ICMJE February 2012
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2012)
Liver-related mortality and liver related morbidity [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2012)
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. [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE VSL#3 and Spontaneous Bacterial Peritonitis
Official Title  ICMJE The Effect of Probiotics on the Incidence of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis and Ascites
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Decompensated Cirrhosis
  • Ascites
Intervention  ICMJE
  • Drug: cotrimoxazole
    Cotrimoxazole 960mg orally each day (two 480mg tablets)
    Other Name: Cotrimoxazole (septrin)
  • Drug: VSL#3 active
    The prescribed dose was 2 sachets (containing 900 billion bacteria) orally each day for 48 weeks
  • Drug: 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
Study Arms  ICMJE
  • Active Comparator: Co-trimoxazole
    Co-trimoxazole 960mg daily po
    Intervention: Drug: cotrimoxazole
  • Experimental: VSL#3 active
    VSL#3 active 2 sachets/daily
    Intervention: Drug: VSL#3 active
  • Placebo Comparator: VSL#3 placebo
    VSL#3 placebo 2 sachets/daily
    Intervention: Drug: VSL#3 placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 27, 2016)
Original Estimated Enrollment  ICMJE
 (submitted: October 4, 2012)
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01701297
Other Study ID Numbers  ICMJE 10GA021
2010-022886-92 ( EudraCT Number )
10/H0405/81 ( Other Identifier: NRES )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Nottingham University Hospitals NHS Trust
Study Sponsor  ICMJE Nottingham University Hospitals NHS Trust
Collaborators  ICMJE VSL Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Martin W James, BM BS FRCP PhD NUH NHS Trust
PRS Account Nottingham University Hospitals NHS Trust
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP