Probiotics in the prevention of antibiotic-associated and C. difficile diarrhoea
| ISRCTN | ISRCTN70017204 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN70017204 |
| Secondary identifying numbers | HTA 06/39/02 |
- Submission date
- 03/04/2009
- Registration date
- 31/07/2009
- Last edited
- 07/06/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
About 1 in 3 older people who are admitted to hospital require treatment with antibiotics. An adverse effect of antibiotics is that they change the "healthy" bacteria that live in the gut. This results in diarrhoea in about 1 in 5 people who are treated with antibiotics. In addition to being distressing for the patient, diarrhoea may delay recovery from illness and prolong the hospital admission. Occasionally, antibiotic treatment results in an overgrowth of a potentially dangerous bacterium called C. difficile. This bacterium can cause a severe diarrhoeal illness that may require additional medical treatment and surgery and may cause death. There is some encouraging evidence that giving supplements of normal, "healthy" bacteria (called probiotics) by mouth together with antibiotics prevents diarrhoea. Probiotics are very safe and do not themselves cause illness in people with a normal immune system. We will use bacteria called lactobacilli that are normally found in the gut in healthy people. We intend to find-out exactly how effective and also how cost-effective this approach is.
Who can participate?
Patients aged 65 or over admitted to hospital and receiving antibiotics
What does the study involve?
Participants are randomly allocated to receive either the probiotic or a placebo (dummy) treatment daily for 21 days in addition to any other treatment. We document how many in each group go on to develop mild and severe diarrhoea and also how this affects their quality of life.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Morriston Hospital (UK)
When is the study starting and how long is it expected to run for?
December 2008 to March 2011
Who is funding the study?
Health Technology Assessment Programme (UK)
Who is the main contact?
Kathie Wareham
kathie.wareham@swansea-tr.wales.nhs.uk
Contact information
Scientific
Clinical Research Unit
Morriston Hospital
Swansea
SA6 6NL
United Kingdom
| Phone | +44 (0)1792 703722 |
|---|---|
| kathie.wareham@swansea-tr.wales.nhs.uk |
Study information
| Study design | Multicentre randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A multicentre, randomised, placebo controlled trial of lactic acid bacteria and bifidobacteria in the prevention of antibiotic-associated diarrhoea (AAD) and Clostridium difficile diarrhoea (CDD) in patients aged 65 years and over admitted to hospital and receiving antibiotics |
| Study acronym | PLACIDE |
| Study hypothesis | A probiotic food supplement is effective in preventing antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital and receiving antibiotics. |
| Ethics approval(s) | Research Ethics Committee for Wales, 27/11/2008 |
| Condition | Antibiotic-associated diarrhoea; C. difficile diarrhoea |
| Intervention | 1. Live bacteria of human origin: 2 strains of Lactobacillus acidophilus (CUL60, National Collection of Industrial, Food and Marine Bacteria [NCIMB] 30157 and CUL21, NCIMB 30156), Bifidobacterium bifidum (CUL20, NCIMB 30153), Bifidobacterium lactis (CUL34, NCIMB 30172). Prepared as lyophilised powder in a capsule containing 6 x 1010 organisms/capsule. 2. Identical formulation of inert placebo: maltodextrin The dose of probiotic is prepared in 5 g lyophilised powder in a capsule - the placebo is a matched capsule with 5 g of maltodextrin. Dosing is daily for 21 days via the oral route. The total duration of follow-up is 8 weeks from the end of antibiotics to a maximum of 12 weeks if other courses of antibiotics are given. |
| Intervention type | Supplement |
| Primary outcome measure | During antibiotic treatment and within 8 weeks of stopping antibiotics: 1. The occurrence of antibiotic associated diarrhoea (AAD) 2. The occurrence of C. difficile diarrhoea (CDD) |
| Secondary outcome measures | 1. Severity and duration of AAD 2. Abdominal symptoms (abdominal pain, bloating, flatus, nausea) 3. Severity and duration of CDD and incidence of recurrence within the study period 4. Incidence of pseudomembranous colitis (PMC), need for colectomy, death 5. Well-being and quality of life 6. Duration of hospital stay 7. Adverse effects 8. Acceptability of the probiotic preparation 9. Viability of the probiotic at point of administration All of these outcomes will be measured during the period from participant recruitment to 8 weeks after stopping antibiotics, to a maximum of 12 weeks from recruitment. 10. Risk factors for ADD, CDD and severe disease (PMC, colectomy, death), assessed at participant recruitment |
| Overall study start date | 01/12/2008 |
| Overall study end date | 01/03/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Sex | Both |
| Target number of participants | 2,974 |
| Participant inclusion criteria | 1. People aged greater than or equal to 65 years, either sex 2. Admitted to hospital without diarrhoea 3. Have been exposed to one or more antibiotics within the last 7 days or are about to start antibiotic treatment |
| Participant exclusion criteria | 1. People with known immunosuppressive disorder, prosthetic heart valve or active inflammatory bowel disease (the latter defined as requiring specific treatment in the past 12 months) 2. Acute pancreatitis (defined as abdominal pain with serum amylase or lipase concentration greater than or equal to three times the institutional upper limit of normal) 3. Jejunal tube in-situ and/or jejunal feeding (as documented in the clinical/nursing records) 4. Likely impaired splanchnic perfusion: any past or current abnormality or disease affecting the mesenteric arteries (as documented in the clinical records) 5. Severe illness requiring care in either a high dependency or intensive care unit (but not planned admission to these facilities for observation only, e.g., after cardiac surgery) 6. People with a previous history of adverse reactions to probiotics 7. Informed consent not granted by patient or their carer(s) |
| Recruitment start date | 01/12/2008 |
| Recruitment end date | 01/03/2011 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
SA6 6NL
United Kingdom
Sponsor information
University/education
Singleton Park
Swansea, West Glamorgan
SA2 8PP
Wales
United Kingdom
| Phone | +44 (0)1792 205678 |
|---|---|
| c.d.jones@swansea.ac.uk | |
| Website | http://www.swansea.ac.uk |
"ROR" |
https://ror.org/053fq8t95 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 06/05/2012 | Yes | No | |
| Results article | results | 12/10/2013 | Yes | No | |
| Results article | results | 01/12/2013 | Yes | No |
Editorial Notes
07/06/2016: Plain English summary added.
