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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-017374-20 | EudraCT Number | ||
| ISRCTN01005546 | Registry Identifier | ISRCTN, http://www.controlled-trials.com/ISRCTN01005546 | |
| DRKS00000084 | Registry Identifier | Deutsches Register Klinischer Studien |
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Masked independent interim analysis: completion of the trial was unlikely.
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| Name | Class |
|---|---|
| German Federal Ministry of Education and Research | OTHER_GOV |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saccharomyces boulardii | Drug | Units: 500 mg per day Route of administration : Oral Use Hard-Capsule |
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| Measure | Description | Time Frame |
|---|---|---|
| Total Number of Antibiotic-associated Diarrhea Episodes | 29 months |
| Measure | Description | Time Frame |
|---|---|---|
| Total Number of Clostridium Difficile-associated Diarrhea Episodes | 29 months | |
| Total Number of Antibiotic-associated Diarrhea Episodes Without Evidence of Clostridium Difficile (Toxins) | 29 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephan Ehrhardt, MD, MPH | Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Abteilung Innere Medizin, Bundeswehrkrankenhaus Ulm | Ulm | Baden-Würtemberg | 89081 | Germany | ||
| I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26973849 | Derived | 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. |
| Label | URL |
|---|---|
| Sponsor website | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Saccharomyces Boulardii | 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 Saccharomyces boulardii: Units: 500 mg per day Route of administration : Oral Use Hard-Capsule |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo | Drug | Placebo |
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| Incidence Density of Antibiotic-associated Diarrhea | 29 months |
| Average Duration of Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea | 29 months |
| Average Number of Bowel Movements in Patients With Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea | 29 months |
| Total Number of Discontinuation or Change of Initially Prescribed Antibiotic | 29 months |
| Hamburg |
| Free and Hanseatic City of Hamburg |
| 20246 |
| Germany |
| Agaplesion Diakonieklinikum Hamburg, Klinik für Innere Medizin | Hamburg | Free and Hanseatic City of Hamburg | 20259 | Germany |
| Bethesda Krankenhaus Bergedorf, Klinik für Innere Medizin | Hamburg | Free and Hanseatic City of Hamburg | 21029 | Germany |
| Klinikum Bremen Ost, Klinik für Innere Medizin | Bremen | Free Hanseatic City of Bremen | 28325 | Germany |
| Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, Zentrum für Pneumologie | Rotenburg (Wümme) | Lower Saxony | 27356 | Germany |
| Klinik und Poliklinik für Innere Medizin, Abteilung für Tropenmedizin und Infektionskrankheiten, Universitätsklinikum Rostock | Rostock | Mecklenburg-Vorpommern | 18057 | Germany |
| Knappschaftskrankenhaus Bottrop, Medizinische Klinik | Bottrop | North Rhine-Westphalia | 46242 | Germany |
| Abteilung Akut-Geriatrie, Ev. Krankenhaus Bethanien Iserlohn | Iserlohn | North Rhine-Westphalia | 58644 | Germany |
| Klinikum Vest GmbH, Behandlungszentrum Paracelsus-Klinik Marl | Marl | North Rhine-Westphalia | 45770 | Germany |
| I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität Mainz | Mainz | Rhineland-Palatinate | 55131 | Germany |
| Klinikum Saarbrücken | Saarbrücken | Saarland | 66119 | Germany |
| Klinikum St.Georg, Klinik für Infektiologie, Tropenmedizin und Nephrologie | Leipzig | Saxony | 04129 | Germany |
| Abt. Innere Medizin, Krankenhaus Reinbek, St. Adolf -Stift | Reinbek | Schleswig-Holstein | 21465 | Germany |
| Microcristallin Cellulose |
Participants received matching placebo twice per day within 24 hours of initiating antibiotic treatment and continued treatment for 7 days after antibiotic discontinuation Placebo: Placebo |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Saccharomyces Boulardii | 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 Saccharomyces boulardii: Units: 500 mg per day Route of administration : Oral Use Hard-Capsule |
| BG001 | Microcristallin Cellulose | Participants received matching placebo twice per day within 24 hours of initiating antibiotic treatment and continued treatment for 7 days after antibiotic discontinuation Placebo: Placebo |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Body height | Mean | Standard Deviation | cm |
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| Body weight | Mean | Standard Deviation | kg |
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| Body mass index | Mean | Standard Deviation | kg/m^2 |
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| C-reactive protein (CRP) | Mean | Standard Deviation | mg/L |
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| Leukocyte count | Mean | Standard Deviation | 10^9 cells/L |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Total Number of Antibiotic-associated Diarrhea Episodes | Posted | Number | Episodes | 29 months |
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| Secondary | Total Number of Clostridium Difficile-associated Diarrhea Episodes | Posted | Number | episodes | 29 months |
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| Secondary | Total Number of Antibiotic-associated Diarrhea Episodes Without Evidence of Clostridium Difficile (Toxins) | Posted | Number | episodes | 29 months |
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| Secondary | Incidence Density of Antibiotic-associated Diarrhea | Posted | Number | cases per year | 29 months |
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| Secondary | Average Duration of Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea | Posted | Mean | Standard Deviation | days | 29 months |
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| Secondary | Average Number of Bowel Movements in Patients With Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea | Posted | Mean | Standard Deviation | bowel movements per day | 29 months |
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| Secondary | Total Number of Discontinuation or Change of Initially Prescribed Antibiotic | Posted | Number | participants | 29 months |
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Ten participants did not take trial drug and were excluded from the safety analysis population. Therefore, the numbers of participants at risk are 245 and 222, while the numbers in the participant flow are 246 and 231.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Saccharomyces Boulardii | 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 Saccharomyces boulardii: Units: 500 mg per day Route of administration : Oral Use Hard-Capsule | 9 | 245 | 9 | 245 | ||
| EG001 | Microcristallin Cellulose | Participants received matching placebo twice per day within 24 hours of initiating antibiotic treatment and continued treatment for 7 days after antibiotic discontinuation Placebo: Placebo | 3 | 222 | 9 | 222 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Duodenal perforation | Gastrointestinal disorders | MedDRA 10.0 |
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| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA 10.0 |
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| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 10.0 |
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| Sudden cardiac death | General disorders | MedDRA 10.0 |
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| Cholecystitis acute | Hepatobiliary disorders | MedDRA 10.0 |
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| Sepsis | Infections and infestations | MedDRA 10.0 |
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| Renal failure | Renal and urinary disorders | MedDRA 10.0 |
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| Pulmonary empyema | Infections and infestations | MedDRA 10.0 |
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| Hepatic cirrhosis | Hepatobiliary disorders | MedDRA 10.0 |
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| Bronchial carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA 10.0 |
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| Gastrointestinal sounds abnormal | Gastrointestinal disorders | MedDRA 10.0 |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 10.0 |
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| Nausea | Gastrointestinal disorders | MedDRA 10.0 |
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| Vomiting | Gastrointestinal disorders | MedDRA 10.0 |
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| Faecal incontinence | Gastrointestinal disorders | MedDRA 10.0 |
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| Flatulence | Gastrointestinal disorders | MedDRA 10.0 |
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| Glossodynia | Gastrointestinal disorders | MedDRA 10.0 |
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| Ileus paralytic | Gastrointestinal disorders | MedDRA 10.0 |
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| Malaise | Gastrointestinal disorders | MedDRA 10.0 |
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| Blood pressure increased | Investigations | MedDRA 10.0 |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 10.0 |
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| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.0 |
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| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 |
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| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA 10.0 |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 10.0 |
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| Oral candidiasis | Infections and infestations | MedDRA 10.0 |
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| Body temperature increased | Investigations | MedDRA 10.0 |
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| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 10.0 |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 10.0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stephan Ehrhardt | Johns Hopkins Bloomberg School of Public Health | 410-502-3872 | sehrhard@jhsph.edu |
| ID | Term |
|---|---|
| D003967 | Diarrhea |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Male |
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| No |
| Superiority or Other |
| Log Rank | 0.87 | No | Superiority or Other |
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