Probiotics for the Prevention of Antibiotics Associated Diarrhoea and Clostridium Difficile Associated Diarrhoea

The investigators aim to investigate whether the routine use of the probiotic formulation VSL#3 co-prescribed with antibiotics reduces the incidence of both Antibiotic associated diarrhoea and Clostridium Difficile associated diarrhoea.

Study Overview

• Status: Completed
• Conditions: Diarrhoea
• Intervention / Treatment: Drug: VSL#3; Drug: Placebo

Detailed Description

The investigators aim to find out whether VSL#3 can prevent Antibiotic associated diarrhoea and Clostridium Difficile associated diarrhoea when VSL#3 is giving during a course of systemic antibiotics. Patients will be randomized in a 1:1 proportion to receive either one sachet of VSL#3 or a similar looking placebo twice a day. This will be given for the length of the antibiotic course and another week thereafter. Follow-up will last until 28 days after the last antibiotic dose. Patient restarted on antibiotics during follow-up will be restarted on the trial medication and the 28 day follow-up will be recommenced.

This trial has 2 co-primary outcome measures.

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom, BS16 1LE
    • Frenchay Hospital
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary
  • Weston-super-Mare, United Kingdom, BS23 4TQ
    • Weston General Hospital
  • Lancashire
    • Wigan, Lancashire, United Kingdom, WN1 2NN
      • Royal Albert Edward Infirmary
  • London
    • Woolwich, London, United Kingdom, SE18 4QH
      • Queen Elizabeth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 18 or older
• Hospital inpatients
• On systemic antibiotics for an infection
• Antibiotics started within last 48 hours

Exclusion Criteria:

• Diarrhoea at screening
• Unable to take enteral meds
• Patients on intensive care units
• Severe Immunosuppression (neutropenia, AIDS, congenital immunoparesis, chemotherapy)
• Risk of endocarditis (Artificial heart valves, history of rheumatic heart disease or infective endocarditis)
• Regular consumption of probiotics until 1 week prior to admission
• Acute severe pancreatitis Persistent vomiting (two days or more)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: VSL#3; Patients will receive one VSL #3 sachets twice a day for the duration of the antibiotic course and for one week after.	Drug: VSL#3; Patients will o receive one VSL #3 sachets twice a day for the duration of the antibiotic course and for one week after.; Other Names: Bifidobacterium breve; Bifidobacterium longum; Bifidobacterium infantis; Lactobacillus acidophilus; Lactobacillus plantarum; Lactobacillus paracasei; Lactobacillus bulgaricus; Streptococcus thermophilus
Placebo Comparator: Placebo; Patients will one placebo sachet twice a day for the duration of the antibiotic course and for one week after.	Drug: Placebo; Patients will one placebo sachet twice a day for the duration of the antibiotic course and for one week after.; Other Names: Maltose based Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Development of antibiotic associated diarrhoea	28 days post last antibiotic dose
Development of Clostridium difficile associated diarrhoea	28 days post last antibiotic dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Length of Hospital Stay	28 days post last antibiotic dose
30-day Mortality	30 days after initiation of therapy

Collaborators and Investigators

• Sponsor: National Health Service, United Kingdom
• Collaborators: Ferring Pharmaceuticals; Hull University Teaching Hospitals NHS Trust; North Bristol NHS Trust; South London and Maudsley NHS Foundation Trust; Wrightington, Wigan and Leigh NHS Foundation Trust
• Investigators: Principal Investigator: Neil Haslam, Wirghtington Wigan and Leigh NHS Trust

Publications and helpful links

General Publications

• Bergogne-Berezin E. Treatment and prevention of antibiotic associated diarrhea. Int J Antimicrob Agents. 2000 Dec;16(4):521-6. doi: 10.1016/s0924-8579(00)00293-4.
• D'Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ. 2002 Jun 8;324(7350):1361. doi: 10.1136/bmj.324.7350.1361.
• Cremonini F, Di Caro S, Nista EC, Bartolozzi F, Capelli G, Gasbarrini G, Gasbarrini A. Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2002 Aug;16(8):1461-7. doi: 10.1046/j.1365-2036.2002.01318.x.
• Selinger CP, Bell A, Cairns A, Lockett M, Sebastian S, Haslam N. Probiotic VSL#3 prevents antibiotic-associated diarrhoea in a double-blind, randomized, placebo-controlled clinical trial. J Hosp Infect. 2013 Jun;84(2):159-65. doi: 10.1016/j.jhin.2013.02.019. Epub 2013 Apr 22.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: September 8, 2009
• First Submitted That Met QC Criteria: September 8, 2009
• First Posted (Estimate): September 9, 2009

Study Record Updates

• Last Update Posted (Estimate): April 26, 2013
• Last Update Submitted That Met QC Criteria: April 25, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Clostridium difficile associated diarrhoea; antibiotic associated diarrhoea
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: WWL - CDiff Prevention; EUDRACT 2008-005244-16