Probiotics in Preventing Antibiotic Associated Diarrhoea Including Clostridium Difficile Infection (NU278)

Antibiotics are currently required to treat patients in hospital when they have an infection, but these antibiotics can cause side effects such as diarrhoea and in some patients a serious form of gut infection with an organism called Clostridium difficile. This organism can produce toxins in the gut causing a severe form of diarrhoea associated with a lot of ill health, and in some circumstances can be fatal. Some studies have shown that yogurts' or Probiotics' (special drinks with a defined concentration of useful bacteria) taken by patients can have a beneficial effect in reducing the diarrhoea associated with antibiotics use. The aim of the present study is to find out whether the use of one of these Probiotics in hospitalised patients taking antibiotics will result in less diarrhoea, less Clostridium difficile infection, as well as cost saving. The study will also analyze the effects of probiotics on quality of life and length of hospital stay.

Study Overview

• Status: Completed
• Conditions: Diarrhoea; Clostridium Difficile
• Intervention / Treatment: Dietary supplement: Probiotic drink containing the live strain; Dietary supplement: placebo probiotic

Detailed Description

As part of this study, we will look at both microbiological and immunological markers, in addition to analyzing the overall cost implications by analysis of health economics.

• Study Type: Interventional
• Enrollment (Actual): 1126
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Ashford, United Kingdom, KT 0PZ
    • Ashford and St Peters Hospital
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Vicotria Hospital
  • Brighton, United Kingdom, BN2 5BE
    • Royal Sussex County Hospital
  • Cambridge, United Kingdom, CB2 2QQ
    • Cambridge University Hospital Trust
  • Chelmsford, United Kingdom, CM1 7HT
    • Broomfield Hospital
  • Chichester, United Kingdom, PO19 6SE
    • St.Richards Hospital
  • Colchester, United Kingdom, CO4 5JL
    • Colchester Hospitals University
  • Ealing, United Kingdom, UB1 3HW
    • Ealing Hospital
  • Eastbourne, United Kingdom, BN21 2YS
    • Eastbourne District General Hospital
  • Frimley, United Kingdom, SW17 7HS
    • Frimley Park Hospital
  • Haywards Heath, United Kingdom, RH16 4EX
    • Princess Royal Hospital
  • Hillingdon, United Kingdom, UB8 3NN
    • Hillingdon Hospital
  • Lancaster, United Kingdom, PR2 9HT
    • Lancashire Teaching Hospital
  • Leicester, United Kingdom, LE2 7LX
    • University Hosppitals of Leicester
  • Lewisham, United Kingdom, SE13 6LH
    • Lewisham Helathcare NHS Trust
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, SW17 0RE
    • St Georges Hospital London
  • Margate, United Kingdom, CT9 4AN
    • Queen Elizabeth Queen Mother Hospital
  • Morecambe, United Kingdom, LA1 4RP
    • University Hospitals of Morecambe Bay
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk and Norwich University
  • Portsmouth, United Kingdom, PO6 3LY
    • Portsmouth Hospitals NHS Trust
  • Redditch, United Kingdom, BN8 7UB
    • Worcestershire Acute Hospitals
  • Redhill, United Kingdom, RH1 5RH
    • East Surrey Hospital
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton
  • Tunbridge Wells, United Kingdom, ME16 9QQ
    • Maidstone and Tunbridge Wells NHS Trust
  • Yeovil, United Kingdom, BA21 4AT
    • Yeovil District Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male/female patients, above 55 years of age Patient has given written informed consent/Assent to take part in the study Patients are receiving antibiotics as inpatients Patients prescribed therapy with single or multiple antibiotics (oral or IV) will be included Antibiotic therapy must be indicated for a minimum of 72 hours Patients must be able to take medication orally Inclusion in the study is approved by the admitting consultant and validated by a member of the trial team within 48 hours

Exclusion Criteria:

• Age less than 55 years Pregnancy Patients on PEG feed. Diarrhoea on admission or within the preceding week Severe life-threatening illness

Subjects with allergy or hypersensitivity to any component of the study product (e.g.: allergy or hypersensitivity to milk proteins) Subjects who had any surgery or intervention in the last 4 weeks Subjects enrolled in another clinical study in the last 4 weeks Subjects who are thought not to comply with the clinical study Subjects presenting with a severe evolving or active pathology or infection of the gastrointestinal tract such as inflammatory bowel disease, Crohn's disease or ulcerative colitis, diverticular disease or liver cirrhosis.

Any condition affecting the pancreas including acute and chronic pancreatitis Patients who had a surgical operation in their bowels in the preceding 3 months A medical condition such that the life expectancy of the patient is predicted at less than 3 months by the admitting consultant and validated by a member of the trial team Immune-suppressed patients (e.g. HIV) Steroid use of Prednisolone greater than 10mg a day (or equivalent of Dexamethasone) for over 2 weeks prior to entering the trial Patients on Cytotoxic drugs Post-transplant patients Any clinical condition affecting the pancreas including acute and chronic pancreatitis Patients with prosthetic heart valves or a history of endocarditis. Patients who have taken probiotic drinks containing live organisms or over the counter probiotic preparations in the past seven days (see Appendix 10) Foreign travel in the last 7 days

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: Dietary supplement Probiotic drink; Double blind Probiotic containing the live strain 100g/day orally, twice daily for the duration of the course of antibiotics plus seven days	Dietary supplement: Probiotic drink containing the live strain; Probiotic drink contains no strain
Placebo Comparator: Dietary supplement probiotic placebo drink; Double blind 'placebo' is actually a control product Placebo drink contains no strain 100gs orally, twice daily for the duration of the course of antibiotics plus seven days	Dietary supplement: placebo probiotic; Placebo product is a sweetened flavoured, non fermented, acidified dairy drink

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of diarrhoea	The incidence of antibiotic associated diarrhoea in the active and placebo group by the end of the follow up period	regular intervals for 28days from entry to trial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence and duration of Clostridium difficile toxin	The incidence and duration of Clostridium difficile toxin detected by ELISA positive testing from a stool sample taken at the onset of diarrhoea in the active and placebo groups	regular intervals for 28 days from entry to trial
The rate of recurrence of antibiotic associated diarrhoea in the active and placebo groups to the end of the follow up period	The rate of recurrence of antibiotic associated diarrhoea in the active and placebo groups to the end of the follow up period	regular intervals for 28 days from entry to trial
rate of recurrence of Clostridium difficile toxin positive diarrhoea	The rate of recurrence of Clostridium difficile toxin positive diarrhoea in the active and placebo groups from hospital discharge until the end of the follow-up period	regular intervals for 28 days from entry to trial
The quality of life in the active and placebo groups at enrollment into the study		regular intervals for 28 days from entry to trial
The length of hospital stay from enrollment into the study until the end of the follow up period in the active and placebo groups The cost-effectiveness as evidenced by health economic calculations		regular intervals for 28 days from entry to trial

Collaborators and Investigators

• Sponsor: University of Sussex
• Collaborators: Danone Institute International
• Investigators: Study Chair: Chakravarthi Rajkumar, University of Sussex

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: March 15, 2010
• First Submitted That Met QC Criteria: March 15, 2010
• First Posted (Estimate): March 16, 2010

Study Record Updates

• Last Update Posted (Actual): March 30, 2020
• Last Update Submitted That Met QC Criteria: March 27, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections
• Other Study ID Numbers: UKCRN7582