Antibiotic-associated DiarrheaPhase 3SacBoNCT01143272
Probiotic Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea
A Phase 3 study testing Saccharomyces boulardii in people with Antibiotic-associated Diarrhea and Clostridium Difficile, run by Bernhard Nocht Institute for Tropical Medicine at 14 sites in Germany.
Trial summary
When patients in hospitals receive antibiotics they often develop diarrhoea. The consequences may be grave for the patient. Thus far, no preventive measure is available. The investigators hypothesize that the apathogenic yeast Saccharomyces boulardii, administered in addition to the antibiotic, may prevent episodes of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antibiotic-associated Diarrhea, Clostridium Difficile, Diarrhea
- What is being tested?
- Saccharomyces boulardii
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 477 participants
- Where
- 14 sitesGermany
- Study dates
- Jun 2010to Oct 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult patient (≥ 18 years)
- patient hospitalized
- patient receives systemic antibiotic treatment
- patient contractually capable
- patient able to follow study procedures
- informed consent of patient
Who cannot join
- allergy against yeast and/or Perenterol® forte und/oder placebos containing Saccharomyces cerevisiae HANSEN CBS 5926, lactose-monohydrate, magnesium stearate, gelatine, sodium dodecyl sulfate, titan dioxide, microcrystalline cellulose.
- central venous catheter
- immunosuppression
- diarrhoea and/or chronic diarrhoea
- regular intake of Perenterol®, Perenterol® forte oder Yomogi® in the last seven days before the start of the study
- systemic antimycotic treatment
Show all 9Show fewer
- systemic antibiotic treatment within the last 6 weeks
- no protection against conception, pregnancy, or lactation
- simultaneous participation in other clinical trials
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Germany14 sites
Knappschaftskrankenhaus Bottrop, Medizinische Klinik
Bottrop, North Rhine-Westphalia, 46242
Klinikum Bremen Ost, Klinik für Innere Medizin
Bremen, Free Hanseatic City of Bremen, 28325
I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, 20246
Agaplesion Diakonieklinikum Hamburg, Klinik für Innere Medizin
Hamburg, Free and Hanseatic City of Hamburg, 20259
Bethesda Krankenhaus Bergedorf, Klinik für Innere Medizin
Hamburg, Free and Hanseatic City of Hamburg, 21029
Abteilung Akut-Geriatrie, Ev. Krankenhaus Bethanien Iserlohn
Iserlohn, North Rhine-Westphalia, 58644
Klinikum St.Georg, Klinik für Infektiologie, Tropenmedizin und Nephrologie
Leipzig, Saxony, 04129
I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität Mainz
Mainz, Rhineland-Palatinate, 55131
Klinikum Vest GmbH, Behandlungszentrum Paracelsus-Klinik Marl
Marl, North Rhine-Westphalia, 45770
Abt. Innere Medizin, Krankenhaus Reinbek, St. Adolf -Stift
Reinbek, Schleswig-Holstein, 21465
Klinik und Poliklinik für Innere Medizin, Abteilung für Tropenmedizin und Infektionskrankheiten, Universitätsklinikum Rostock
Rostock, Mecklenburg-Vorpommern, 18057
Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, Zentrum für Pneumologie
Rotenburg (Wümme), Lower Saxony, 27356
Klinikum Saarbrücken
Saarbrücken, Saarland, 66119
Abteilung Innere Medizin, Bundeswehrkrankenhaus Ulm
Ulm, Baden-Würtemberg, 89081
About this study
Official title: Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea - Randomised, Double-blind, Placebo-controlled Trial
When patients in hospitals receive antibiotics they often develop diarrhoea. The consequences may be grave for the patient. Thus far, no preventive measure is available. The investigators hypothesize that the apathogenic yeast Saccharomyces boulardii, administered in addition to the antibiotic, may prevent episodes of diarrhoea or may lead to less pronounced diarrhoea. To test this hypothesis, the investigators are carrying out a clinical trial in 1520 adult patients in several hospitals.
Read the detailed description
Antibiotic-associated diarrhoea (AAD) is a frequent condition in hospitalised patients receiving antibiotic treatment. The same is true for Clostridium difficile-associated diarrhoea (CDAD) with even more grave consequences of increased morbidity and mortality. 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 beneficial for the prevention of AAD and CDAD. However, data have so far been inconclusive and recently published meta-analyses strongly recommended large state-of-the-art clinical trials on probiotic substances for the prevention of AAD and CDAD. Since the efficacy, side-effects and modes of action of different probiotic bacteria and yeast are strain specific, benefits and risks cannot be generalised. The non-pathogenic yeast Saccharomyces cerevisiae var. boulardii (Sac. boulardii) is considered the most promising probiotic substance for the prevention of AAD and CDAD. We carry out a randomised, placebo controlled, double blind multicentre clinical trial to evaluate Sac. boulardii for the indication of prevention of AAD and CDAD in 1520 adult, hospitalised patients.
- Being tested
- Saccharomyces boulardii, Placebo
- Keywords
- antibiotic, associated, diarrhoea, saccharomyces boulardii, Antibiotic-associated diarrhoea (AAD), Clostridium difficile-associated-diarrhoea (CDAD)
- Medical subject headings
- Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saccharomyces boulardiiDrug
Also called Perenterol® Forte
Units: 500 mg per day Route of administration : Oral Use Hard-Capsule
PlaceboDrug
Also called Microcristallin cellulose, Matching capsules containing no active ingredients
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Saccharomyces boulardii | Active comparator | Participants received Saccharomyces boulardii 250 mg capsules twice per day within 24 hours of initiating antibiotic treatment and continued treatment for 7 days after antibiotic discontinuation Receives: Drug: Saccharomyces boulardii |
| Microcristallin cellulose | Placebo comparator | Participants received matching placebo twice per day within 24 hours of initiating antibiotic treatment and continued treatment for 7 days after antibiotic discontinuation Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Antibiotic-associated Diarrhea Episodes
Measured: 29 months
Secondary outcomes (6)
Total Number of Clostridium Difficile-associated Diarrhea Episodes
Measured: 29 months
Total Number of Antibiotic-associated Diarrhea Episodes Without Evidence of Clostridium Difficile (Toxins)
Measured: 29 months
Incidence Density of Antibiotic-associated Diarrhea
Measured: 29 months
Average Duration of Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea
Measured: 29 months
Average Number of Bowel Movements in Patients With Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea
Measured: 29 months
Total Number of Discontinuation or Change of Initially Prescribed Antibiotic
Measured: 29 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2010 (estimated)
- Study startJun 2010
- Primary completionOct 2012
- Study completionOct 2012
Why it stopped: Masked independent interim analysis: completion of the trial was unlikely.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Antibiotic-associated DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 477 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bernhard Nocht Institute for Tropical Medicine
- Sponsor type
- Other government
- Collaborators
- German Federal Ministry of Education and Research
- Responsible party
- Principal investigator, Stephan Ehrhardt, Bernhard Nocht Institute for Tropical Medicine
- Investigators
- Stephan Ehrhardt, MD, MPH, Principal investigator, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01143272
- Sponsor's protocol ID
- BNI-2009-01
- Other IDs
- 2009-017374-20, ISRCTN01005546, DRKS00000084, 2009
- Acronym
- SacBo
- Status last verified
- Jun 2016
- First submitted
- 11 Jun 2010
- Last updated
- 18 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Ehrhardt S, Guo N, Hinz R, Schoppen S, May J, Reiser M, Schroeder MP, Schmiedel S, Keuchel M, Reisinger EC, Langeheinecke A, de Weerth A, Schuchmann M, Schaberg T, Ligges S, Eveslage M, Hagen RM, Burchard GD, Lohse AW. Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial. Open Forum Infect Dis. 2016 Jan 29;3(1):ofw011. doi: 10.1093/ofid/ofw011. eCollection 2016 Jan.
PubMed 26973849
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea - Randomised, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT01143272
- Acronym / sponsor ID
- SacBo / BNI-2009-01
- Keywords
- antibiotic, associated, diarrhoea, saccharomyces boulardii, Antibiotic-associated diarrhoea (AAD), Clostridium difficile-associated-diarrhoea (CDAD)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Masked independent interim analysis: completion of the trial was unlikely.
- Enrolment
- 477 participants (actual)
- Lead sponsor
- Bernhard Nocht Institute for Tropical MedicineOther government
- Collaborators
- German Federal Ministry of Education and Research
- Study start
- Jun 2010
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 14 Jun 2010 (estimated)
- Results
- Posted 18 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
When patients in hospitals receive antibiotics they often develop diarrhoea. The consequences may be grave for the patient. Thus far, no preventive measure is available. The investigators hypothesize that the apathogenic yeast Saccharomyces boulardii, administered in addition to the antibiotic, may prevent episodes of diarrhoea or may lead to less pronounced diarrhoea. To test this hypothesis, the investigators are carrying out a clinical trial in 1520 adult patients in several hospitals.
Detailed description
Antibiotic-associated diarrhoea (AAD) is a frequent condition in hospitalised patients receiving antibiotic treatment. The same is true for Clostridium difficile-associated diarrhoea (CDAD) with even more grave consequences of increased morbidity and mortality. 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 beneficial for the prevention of AAD and CDAD. However, data have so far been inconclusive and recently published meta-analyses strongly recommended large state-of-the-art clinical trials on probiotic substances for the prevention of AAD and CDAD. Since the efficacy, side-effects and modes of action of different probiotic bacteria and yeast are strain specific, benefits and risks cannot be generalised. The non-pathogenic yeast Saccharomyces cerevisiae var. boulardii (Sac. boulardii) is considered the most promising probiotic substance for the prevention of AAD and CDAD. We carry out a randomised, placebo controlled, double blind multicentre clinical trial to evaluate Sac. boulardii for the indication of prevention of AAD and CDAD in 1520 adult, hospitalised patients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Saccharomyces boulardii | Active comparator | Drug: Saccharomyces boulardiiParticipants received Saccharomyces boulardii 250 mg capsules twice per day within 24 hours of initiating antibiotic treatment and continued treatment for 7 days after antibiotic discontinuation |
| Microcristallin cellulose | Placebo comparator | Drug: PlaceboParticipants received matching placebo twice per day within 24 hours of initiating antibiotic treatment and continued treatment for 7 days after antibiotic discontinuation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- adult patient (≥ 18 years)
- patient hospitalized
- patient receives systemic antibiotic treatment
- patient contractually capable
- patient able to follow study procedures
Key exclusion criteria (9 listed)
- allergy against yeast and/or Perenterol® forte und/oder placebos containing Saccharomyces cerevisiae HANSEN CBS 5926, lactose-monohydrate, magnesium stearate, gelatine, sodium dodecyl sulfate, titan dioxide, microcrystalline cellulose.
- central venous catheter
- immunosuppression
- diarrhoea and/or chronic diarrhoea
- regular intake of Perenterol®, Perenterol® forte oder Yomogi® in the last seven days before the start of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Saccharomyces boulardiiAlso: Perenterol® ForteUnits: 500 mg per day Route of administration : Oral Use Hard-Capsule | Drug | Saccharomyces boulardii |
| PlaceboAlso: Microcristallin cellulose, Matching capsules containing no active ingredientsPlacebo | Drug | Microcristallin cellulose |
Primary outcome
Total Number of Antibiotic-associated Diarrhea Episodes
Time frame: 29 months
6 secondary outcomes
Total Number of Clostridium Difficile-associated Diarrhea Episodes
Time frame: 29 months
Total Number of Antibiotic-associated Diarrhea Episodes Without Evidence of Clostridium Difficile (Toxins)
Time frame: 29 months
Incidence Density of Antibiotic-associated Diarrhea
Time frame: 29 months
Average Duration of Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea
Time frame: 29 months
Average Number of Bowel Movements in Patients With Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea
Time frame: 29 months
Total Number of Discontinuation or Change of Initially Prescribed Antibiotic
Time frame: 29 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26973849Ehrhardt S, Guo N, Hinz R, Schoppen S, May J, Reiser M, Schroeder MP, Schmiedel S, Keuchel M, Reisinger EC, Langeheinecke A, de Weerth A, Schuchmann M, Schaberg T, Ligges S, Eveslage M, Hagen RM, Burchard GD, Lohse AW. Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial. Open Forum Infect Dis. 2016 Jan 29;3(1):ofw011. doi: 10.1093/ofid/ofw011. eCollection 2016 Jan.
- Sponsor websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephan Ehrhardt, MD, MPH principal investigator
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Saccharomyces boulardii in people with Antibiotic-associated Diarrhea and Clostridium Difficile, run by Bernhard Nocht Institute for Tropical Medicine at 14 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Number of Antibiotic-associated Diarrhea Episodes (time frame: 29 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01143272, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2016.