Back to resultsVSL#3 and Spontaneous Bacterial Peritonitis
Primary Purpose
Decompensated Cirrhosis, Ascites
Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
cotrimoxazole
VSL#3 active
VSL#3 placebo
Sponsored by
About this trial
This is an interventional treatment trial for Decompensated Cirrhosis focused on measuring Cirrhosis, ascites, infection
Eligibility 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
Sites / Locations
- NUH NHS Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Placebo Comparator
Arm Label
Co-trimoxazole
VSL#3 active
VSL#3 placebo
Arm Description
Co-trimoxazole 960mg daily po
VSL#3 active 2 sachets/daily
VSL#3 placebo 2 sachets/daily
Outcomes
Primary Outcome Measures
Liver-related mortality and liver related morbidity
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.
Full Information
NCT ID
NCT01701297
First Posted
August 8, 2012
Last Updated
October 27, 2016
Sponsor
Nottingham University Hospitals NHS Trust
Collaborators
VSL Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01701297
Brief Title
VSL#3 and Spontaneous Bacterial Peritonitis
Official Title
The Effect of Probiotics on the Incidence of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis and Ascites
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Terminated
Why Stopped
Unable to obtain QP release certification from the manufacturer (VSL3) for shipment of IMP
Study Start Date
February 2012 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nottingham University Hospitals NHS Trust
Collaborators
VSL Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Decompensated Cirrhosis, Ascites
Keywords
Cirrhosis, ascites, infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Co-trimoxazole
Arm Type
Active Comparator
Arm Description
Co-trimoxazole 960mg daily po
Arm Title
VSL#3 active
Arm Type
Experimental
Arm Description
VSL#3 active 2 sachets/daily
Arm Title
VSL#3 placebo
Arm Type
Placebo Comparator
Arm Description
VSL#3 placebo 2 sachets/daily
Intervention Type
Drug
Intervention Name(s)
cotrimoxazole
Other Intervention Name(s)
Cotrimoxazole (septrin)
Intervention Description
Cotrimoxazole 960mg orally each day (two 480mg tablets)
Intervention Type
Drug
Intervention Name(s)
VSL#3 active
Intervention Description
The prescribed dose was 2 sachets (containing 900 billion bacteria) orally each day for 48 weeks
Intervention Type
Drug
Intervention Name(s)
VSL#3 placebo
Intervention Description
This was two placebo sachets identical to VSL#3 active sachet. The prescribed dose was 2 sachets orally each day for 48 weeks
Primary Outcome Measure Information:
Title
Liver-related mortality and liver related morbidity
Time Frame
12 months
Secondary Outcome Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin W James, BM BS FRCP PhD
Organizational Affiliation
NUH NHS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
NUH NHS Trust
City
Nottingham
State/Province
Nottinghamshire
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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VSL#3 and Spontaneous Bacterial Peritonitis
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