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VSL#3 and Spontaneous Bacterial Peritonitis

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ClinicalTrials.gov 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
Sponsor:
Collaborator:
VSL Pharmaceuticals
Information provided by (Responsible Party):
Nottingham University Hospitals NHS Trust

Study Description
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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.


Condition or disease Intervention/treatment Phase
Decompensated Cirrhosis Ascites Drug: cotrimoxazole Drug: VSL#3 active Drug: VSL#3 placebo Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Probiotics on the Incidence of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis and Ascites
Study Start Date : February 2012
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Co-trimoxazole
Co-trimoxazole 960mg daily po
 Drug: cotrimoxazole
Cotrimoxazole 960mg orally each day (two 480mg tablets)
Other Name: Cotrimoxazole (septrin)
Experimental: VSL#3 active
VSL#3 active 2 sachets/daily
 Drug: VSL#3 active
The prescribed dose was 2 sachets (containing 900 billion bacteria) orally each day for 48 weeks
Placebo Comparator: VSL#3 placebo
VSL#3 placebo 2 sachets/daily
 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


Outcome Measures
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Primary Outcome Measures :
  1. Liver-related mortality and liver related morbidity [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01701297


Locations
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United Kingdom
NUH NHS Trust
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
Nottingham University Hospitals NHS Trust
VSL Pharmaceuticals
Investigators
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Principal Investigator: Martin W James, BM BS FRCP PhD NUH NHS Trust
More Information
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Responsible Party: Nottingham University Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01701297    
Other Study ID Numbers: 10GA021
2010-022886-92 ( EudraCT Number )
10/H0405/81 ( Other Identifier: NRES )
First Posted: October 5, 2012    Key Record Dates
Last Update Posted: October 28, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Nottingham University Hospitals NHS Trust:
Cirrhosis, ascites, infection
Additional relevant MeSH terms:
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Peritonitis
Liver Cirrhosis
Fibrosis
Ascites
Pathologic Processes
Liver Diseases
Digestive System Diseases
Intraabdominal Infections
Infection
 Peritoneal Diseases
Trimethoprim, Sulfamethoxazole Drug Combination
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Anti-Bacterial Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents