Plain English Summary
Background and study aims
In the year 2006 37,3 million prescriptions of antibiotics were registered in Germany. Antibiotics are among the most prescribed drugs in this country. Antibiotic associated diarrhoea (AAD) is a frequent and severe condition. It appears in 10-25% of patients in hospitals undergoing antibiotic treatment and results not only in longer hospitalisation but also a higher risk for further complications. Clostridium difficile- associated diarrhoea (CDAD) is an especially severe form of AAD and occurs in 15-25% of all cases of AAD. Clostridium difficile is a naturally occurring bacteria of the healthy intestinal flora. Under suppression of the normal intestinal flora due to antibiotic treatment Clostridium difficile can grow and secrete toxins causing damage to the intestinal tissue. Patients suffering from a CDAD not only undergo a distinctive diarrhoea but may also develop life-threatening complications, e.g. pseudomembraneous colitis or toxic megacolon. AAD and CDAD are also a financial burden to the health care system. The development and evaluation of preventive strategies is one key public health challenge. In the absence of clinically evaluated alternatives, probiotics have been suggested to be help prevent
AAD and CDAD. However, data have so far been inconclusive and recently published analyses strongly recommended that large clinical trials should be run. Perenterol® forte is a non-prescription substance approved in Germany for symptomatic treatment of diarrhoea and treatment or prevention of travellers' diarrhoea or diarrhoea due to tube feeding. The active ingredient is Saccharomyces boulardii. Saccharomyces boulardii is considered the most promising probiotic substance for the prevention of AAD and CDAD and is the object of this trial.
Who can participate?
Every contractually capable adult who receives systemic (oral/intravenous) antibiotic treatment while hospitalised in one of our trial centres can participate after signing the written consent form, as long as they comply with inclusion and exclusion criteria.
What does the study involve?
Patients receive the drug Perenterol® forte or a dummy drug twice daily. The capsules are taken orally for the duration and one week following antibiotic treatment. The patient independently records his/her stool frequency and consistence in a diary during the treatment and for another 6 weeks after the treatment.
What are the possible benefits and risks of participating?
Risks due to participation in this trial are minimal.
Sac. boulardii is a living micro-organism which is able to cause generalized fungal infections under adverse circumstances (e.g. immune deficiency) by migration from the gastrointestinal tract into the blood stream or by external contamination of central venous catheters. Individual cases of these generalized fungal infections have been detected in hospitalised patients with central venous catheters additionally suffering from a severe underlying disease mostly localised in the gastrointestinal tract. Known side effects are flatulence and hypersensitivity reactions to the point of anaphylactic shock or sepsis.
Where is the study run from?
A number of German centres
When is study starting and how long is it expected to run for?
The recruitment started in June 2010. The first patient was recruited on 09/07/2010. The estimated end date of the study is 31/07/2012.
Who is funding the study?
German Federal Ministry of Education and Research (BMBF)
Who is the main contact?
Dr. Stephan Ehrhardt, Lead Investigator, email@example.com
Rebecca Hinz, Clinical Project Manager, firstname.lastname@example.org
Dr. Stefanie Schoppen, Project Manager, email@example.com
Saccharomyces boulardii for the prevention of antibiotic-associated diarrhoea: a randomised placebo-controlled multicentre phase III trial
Evaluation of the efficacy of Saccharomyces boulardii for the prevention of antibiotic-associated diarrhoea in hospitalised, adult patients.
As of 22/03/2012, the trial record has been amended.
Previous target number of participants:1520 (first patient in on 09/07/2010; Initiation visits: 18 trial sites, Currently recruiting trial sites: 11, Suspended/withdrawn trial sites: 7)
Current target number of participants: 1520 (first patient in on 09/07/2010; Initiation visits: 18 trial sites, Currently recruiting trial sites: 7, Suspended/withdrawn trial sites: 11)
Anticipated end date has been updated from 31/07/2012 to 31/01/2013.
As of 25/07/2012, the following changes have been made to this record:
1. The anticipated end date has been updated to 31/07/2013 from 31/01/2013
Ethikkommission der Ärztekammer Hamburg, Humboldtstr. 67a, 22083 Hamburg on 19/04/2010 (Ref: PVN 3440)
Randomised double-blind placebo-controlled multicentre phase III clinical trial, adaptive study design
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Use the contact details below to request a patient information sheet or visit the trial website
250 mg oral Saccharomyces boulardii twice daily (bid) versus corresponding placebo during antibiotic treatment until 7 days after completion of antibiotic treatment.
07/12/2012: Please note that this trial was stopped on 01/11/2012. Number of trial sites: 18, initiation visits, recruitment till termination: 7, termination of trial sites while study was ongoing: 8, withdrawn trial sites: 3
Primary outcome measures
Cumulative incidence of any antibiotic-associated diarrhoea, measured at the end of the study
Secondary outcome measures
1. Cumulative incidence of Clostridium difficile-associated diarrhoea
2. Cumulative incidence of antibiotic-associated diarrhoea without evidence of Clostridium difficile (toxins)
3. Cumulative incidence of Clostridium difficile-associated diarrhoea among all antibiotic-associated diarrhoeas
4. Influence of initial white blood cell count and c-reactive protein on the incidence of antibiotic-associated diarrhoea
5. Hazard rate of antibiotic-associated diarrhoea and Clostridium difficile-associated diarrhoea
6. Mean duration of antibiotic-associated diarrhoea and Clostridium difficile-associated diarrhoea
7. Mean stool frequency in patients with antibiotic-associated diarrhoea and Clostridium difficile-associated diarrhoea
8. Cumulative incidence of change of initially prescribed antibiotic
All measured at the end of the study.
Overall trial start date
Overall trial end date
Objectives no longer viable
Participant inclusion criteria
1. Adult, hospitalised patients receiving systemic antibiotic treatment
2. Written informed consent
3. Aged over 18 years, either sex
Target number of participants
Target number of participants:1520 (477 recruited when trial stopped)
Participant exclusion criteria
1. Allergy against Saccharomyces boulardii
2. Central venous catheter
4. Chronic diarrhoea
5. Regular intake of Saccharomyces boulardii before beginning of the study
6. Systemic antimycotic treatment
7. Systemic antibiotic treatment within the last 6 weeks
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Bernhard Nocht Institute for Tropical Medicine (Germany)
German Federal Ministry of Education and Research (Bundesministerium Fur Bildung und Forschung [BMBF]) (Germany) (ref: 01 KG 0902)
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting