Condition category
Digestive System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Antibiotics are used in many conditions and are often given to patients to protect them against infection at the time of surgery. Diarrhoea can occur after the use of antibiotics and is a common problem that is difficult to avoid. It can delay recovery from surgery and in the worst cases can be a serious problem for the patient’s health. Evidence is emerging that probiotics, ‘friendly’ bacteria usually in special drinks or yoghurts, might reduce this risk. The aim in this study is to investigate whether a daily bottle of Yakult, compared with placebo, can reduce the rate of antibiotic-associated diarrhoea in patients having planned orthopaedic surgery at the Elective Orthopaedic Centre (UK).

Who can participate?
Patients who have been referred for an elective orthopaedic operation at the Elective Orthopaedic Centre (UK).

What does the study involve?
Patients will be randomly allocated to one of two groups: Yakult or placebo. They will need to refrain from consuming any probiotics in the 8 weeks before their surgery. They might be telephoned around 3 weeks before the operation as a reminder, and to check that nothing has changed and that they still meet the criteria for entry into the study. Patients will then be provided with a supply of Yakult or placebo and should start drinking one bottle per day for 2 weeks before the surgery and for a further 2 weeks after the surgery, recording this information on the sheets provided.
The operation and treatments will proceed as normal and patients’ care will be as standard. After the operation, and for the next 4 weeks, patients will need to record their stool appearance using a chart that they will be provided with. If they have diarrhoea in the 4 weeks following the operation, as defined by three or more watery stools on two or more consecutive days, they will need to inform us by telephone or email and send a stool sample for testing. This testing is part of the patients’ clinical care because diarrhoea can be serious in some cases and can be treated if the stool sample shows the cause.
Patients will also need to complete a questionnaire about gastrointestinal symptoms, which will be short and simple, at the time of providing consent, in the hospital 2 weeks and and 4 weeks after surgery.

What are the possible benefits and risks of participating?
The main possible benefit would be a reduced risk of antibiotic-associated diarrhoea, which could otherwise prolong recovery from surgery and could be detrimental to health.
There are no known safety issues surrounding this study.

Where is the study run from?
Epsom General Hospital, Elective Orthopaedic Centre (UK)

When is the study starting and how long is it expected to run for?
From April 2010 to August 2014

Who is funding the study?
Yakult Ltd (UK), Elective Orthopaedic Centre (UK) and St George's Charitable Trust (UK)

Who is the main contact?
Dr Carl Moran

Trial website

Contact information



Primary contact

Dr Carl Moran


Contact details

St. Richard's Hospital
Spitalfield Lane
PO19 6SE
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Effects of Yakult (Lactobacillus casei Shirota) on prevention of antibiotic-associated diarrhoea and Clostridium difficile infection in patients undergoing elective orthopaedic surgery


Study hypothesis

Maintenance of a healthy commensal microbiota and the gut’s colonisation resistance by the administration of once daily probiotic Lactobacillus casei Shirota in the form of fermented milk (Yakult), before and after elective orthopaedic surgery, can help reduce the risk of diarrhoea associated with antibiotics and Clostridium difficile.

Ethics approval

National Research Ethics Service, North London REC 3, approval date 27/09/2010, REC reference number: 10/H0709/52

Study design

Single-centre double-blind randomised placebo-controlled study

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.




Patients will be randomly allocated to one of two groups. One group will receive a daily Yakult drink for 2 weeks before and 2 weeks after the elective operation. The other group will receive a placebo version of the drink for the same period. The placebo drink will not have the active ingredient of Yakult, but will look and taste identical and will be packaged in the same way. The placebo drink will also be manufactured by Yakult.

Intervention type



Drug names

Primary outcome measures

Incidence of antibiotic-associated diarrhoea during 4 weeks after surgery. This will be assessed in a hospital and then reported by participants following discharge through direct contact with us or records of their bowel habits over the 4 weeks following the operation. The stool chart will then be sent back to us in a pre-paid envelope.

Secondary outcome measures

1. Duration of antibiotic-associated diarrhoea: this will either be recorded directly if the diarrhoea occurs while the patient is still in hospital or by the participant on a stool chart that covers the 4 weeks after the operation. The recorded information is then sent back by the participant in a pre-paid envelope.
2. The incidence of Clostridium difficile diarrhoea, as diagnosed with a positive Clostridium difficile toxin test and stool culture to exclude other enteric pathogens in all patients with undiagnosed diarrhoea. Any inpatients with diarrhoea will have a stool sample sent for analysis, as per standard hospital care. Participants are asked to inform us of the diarrhoea if it occurs in the 4 weeks after surgery, but following discharge from hospital, so that they can have a stool sample taken (as part of standard care).
3. Participants will have their gastrointestinal symptoms recorded both before and after surgery with the Gastrointestinal Symptom Rating Scale. They will have them recorded face-to-face at the time of consent and at the time of the operation. Participants will record the symptoms themselves at 2 weeks and 4 weeks after the surgery and will send these results to us in pre-paid envelopes.

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Undergoing elective joint replacement surgery at the Elective Orthopaedic Centre (UK)
2. Must be able to adhere to the protocol requirements
3. Must be capable of giving informed consent
4. At least 18 years old

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Diarrhoea on pre-admission or within the preceding week
2. Lactose intolerance or intolerance to dairy products
3. Regular probiotic consumption in the previous 8 weeks
4. Antibiotic use in the previous 4 weeks
5. Patients unable to give written informed consent
6. Immunosuppression
7. Active inflammatory bowel disease or bowel surgery less than 6 months ago, cancer, leukaemia or pancreatitis

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Epsom General Hospital
Elective Orthopaedic Centre Denbies Wing Surrey
KT18 7EG
United Kingdom

Sponsor information


St George's University of London

Sponsor details

Cranmer Terrace
SW17 0RE
United Kingdom

Sponsor type




Funder type


Funder name

Yakult UK Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Elective Orthopaedic Centre (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

St George's Charitable Trust (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

To be confirmed at a later date.

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes