Condition category
Digestive System
Date applied
08/02/2010
Date assigned
07/06/2010
Last edited
07/12/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

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, ehrhardt@bni-hamburg.de
Rebecca Hinz, Clinical Project Manager, hinz@bni-hamburg.de
Dr. Stefanie Schoppen, Project Manager, schoppen@bni-hamburg.de

Trial website

http://www.clinicaltrial-sacbo.de

Contact information

Type

Scientific

Primary contact

Dr Stephan Ehrhardt

ORCID ID

Contact details

Bernhard-Nocht-Strasse 74
Hamburg
20395
Germany

Additional identifiers

EudraCT number

2009-017374-20

ClinicalTrials.gov number

NCT01143272

Protocol/serial number

BNI-2009-01

Study information

Scientific title

Saccharomyces boulardii for the prevention of antibiotic-associated diarrhoea: a randomised placebo-controlled multicentre phase III trial

Acronym

SacBo

Study hypothesis

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

Ethics approval

Ethikkommission der Ärztekammer Hamburg, Humboldtstr. 67a, 22083 Hamburg on 19/04/2010 (Ref: PVN 3440)

Study design

Randomised double-blind placebo-controlled multicentre phase III clinical trial, adaptive study design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Use the contact details below to request a patient information sheet or visit the trial website

Condition

Antibiotic-associated diarrhoea

Intervention

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

Intervention type

Drug

Phase

Phase III

Drug names

Saccharomyces boulardii

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

01/06/2010

Overall trial end date

01/11/2012

Reason abandoned

Objectives no longer viable

Eligibility

Participant inclusion criteria

1. Adult, hospitalised patients receiving systemic antibiotic treatment
2. Written informed consent
3. Aged over 18 years, either sex

Participant type

Patient

Age group

Adult

Gender

Both

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
3. Immunosuppression
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
8. Pregnancy

Recruitment start date

01/06/2010

Recruitment end date

01/11/2012

Locations

Countries of recruitment

Germany

Trial participating centre

Bernhard-Nocht-Strasse 74
Hamburg
20395
Germany

Sponsor information

Organisation

Bernhard Nocht Institute for Tropical Medicine (Germany)

Sponsor details

Bernhard-Nocht-Strasse 74
Hamburg
20395
Germany

Sponsor type

Research organisation

Website

http://www15.bni-hamburg.de/bni/bni2/neu2/getfile.acgi?area_engl=welcome&pid=00

Funders

Funder type

Research organisation

Funder name

German Federal Ministry of Education and Research (Bundesministerium Fur Bildung und Forschung [BMBF]) (Germany) (ref: 01 KG 0902)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication summary

Publication citations

Additional files

Editorial Notes