VSL#3 and Spontaneous Bacterial Peritonitis

This study is currently recruiting participants.
Verified October 2012 by Nottingham University Hospitals NHS Trust
Sponsor:
Collaborator:
VSL Pharmaceuticals
Information provided by (Responsible Party):
Nottingham University Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01701297
First received: August 8, 2012
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Decompensated Cirrhosis With Ascites.
Drug: cotrimoxazole
Drug: VSL#3 active
Drug: VSL#3 placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Probiotics on the Incidence of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis and Ascites

Resource links provided by NLM:


Further study details as provided by Nottingham University Hospitals NHS Trust:

Primary Outcome Measures:
  • Liver-related mortality and liver related morbidity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 51
Study Start Date: February 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Co-trimoxazole
Co-trimoxazole 960mg daily po
Drug: cotrimoxazole
Other Name: Cotrimoxazole (septrin)
Experimental: VSL#3 active
VSL#3 active 2 sachets/daily
Drug: VSL#3 active
Placebo Comparator: VSL#3 placebo
VSL#3 placebo 2 sachets/daily
Drug: VSL#3 placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01701297

Contacts
Contact: Martin W James, BM BS FRCP PhD +44 115 9249924 ext 63443 martin.james@nuh.nhs.uk
Contact: Indra N Guha, PhD +44 115 9249924 ext 63443 Neil.guha@nottingham.ac.uk

Locations
United Kingdom
NUH NHS Trust Recruiting
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Contact: Brian Thomson, PhD    +44 1159709049    brian.thomson@nottingham.ac.uk   
Contact: Maria Koufali, PhD    +44 1159709049    maria.koufali@nuh.nhs.uk   
Sponsors and Collaborators
Nottingham University Hospitals NHS Trust
VSL Pharmaceuticals
Investigators
Principal Investigator: Martin W James, BM BS FRCP PhD NUH NHS Trust
  More Information

No publications provided

Responsible Party: Nottingham University Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01701297     History of Changes
Other Study ID Numbers: 10GA021, 2010-022886-92, 10/H0405/81
Study First Received: August 8, 2012
Last Updated: October 4, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Nottingham University Hospitals NHS Trust:
Cirrhosis, ascites, infection

Additional relevant MeSH terms:
Ascites
Liver Cirrhosis
Fibrosis
Peritonitis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Peritoneal Diseases
Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on April 15, 2014