Clinical trial NCT01143272: Probiotic Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea
Official title: Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea - Randomised, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Antibiotic-associated Diarrhea
Clostridium Difficile
Diarrhea
Keywords: antibiotic
associated
diarrhoea
saccharomyces boulardii
Antibiotic-associated diarrhoea (AAD)
Clostridium difficile-associated-diarrhoea (CDAD)
Lead sponsor: Bernhard Nocht Institute for Tropical Medicine
Sponsor class: OTHER_GOV
Collaborators: name: German Federal Ministry of Education and Research
First posted: 2010-06-14
Enrollment: 477
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* adult patient (≥ 18 years)
* patient hospitalized
* patient receives systemic antibiotic treatment
* patient contractually capable
* patient able to follow study procedures
* informed consent of patient

Exclusion Criteria:

* 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
* systemic antibiotic treatment within the last 6 weeks
* no protection against conception, pregnancy, or lactation
* simultaneous participation in other clinical trials

Primary outcomes:
measure: Total Number of Antibiotic-associated Diarrhea Episodes
timeFrame: 29 months
Secondary outcomes:
measure: Total Number of Clostridium Difficile-associated Diarrhea Episodes
timeFrame: 29 months
measure: Total Number of Antibiotic-associated Diarrhea Episodes Without Evidence of Clostridium Difficile (Toxins)
timeFrame: 29 months
measure: Incidence Density of Antibiotic-associated Diarrhea
timeFrame: 29 months
measure: Average Duration of Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea
timeFrame: 29 months
measure: Average Number of Bowel Movements in Patients With Antibiotic-associated Diarrhoea and Clostridium Difficile-associated Diarrhea
timeFrame: 29 months
measure: Total Number of Discontinuation or Change of Initially Prescribed Antibiotic
timeFrame: 29 months
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: Abteilung Innere Medizin, Bundeswehrkrankenhaus Ulm
state: Baden-Würtemberg
city: Rostock
country: Germany
facility: Klinik und Poliklinik für Innere Medizin, Abteilung für Tropenmedizin und Infektionskrankheiten, Universitätsklinikum Rostock
state: Mecklenburg-Vorpommern
city: Rotenburg
country: Germany
facility: Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, Zentrum für Pneumologie
state: Niedersachsen
city: Bottrop
country: Germany
facility: Knappschaftskrankenhaus Bottrop, Medizinische Klinik
state: Nordrhein-Westfalen
city: Iserlohn
country: Germany
facility: Abteilung Akut-Geriatrie, Ev. Krankenhaus Bethanien Iserlohn
state: Nordrhein-Westfalen
city: Marl
country: Germany
facility: Klinikum Vest GmbH, Behandlungszentrum Paracelsus-Klinik Marl
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität Mainz
state: Rheinland-Pfalz
city: Saarbrücken
country: Germany
facility: Klinikum Saarbrücken
state: Saarland
city: Leipzig
country: Germany
facility: Klinikum St.Georg, Klinik für Infektiologie, Tropenmedizin und Nephrologie
state: Sachsen
city: Reinbek
country: Germany
facility: Abt. Innere Medizin, Krankenhaus Reinbek, St. Adolf -Stift
state: Schleswig-Holstein
city: Bremen
country: Germany
facility: Klinikum Bremen Ost, Klinik für Innere Medizin
city: Hamburg
country: Germany
facility: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Agaplesion Diakonieklinikum Hamburg, Klinik für Innere Medizin
city: Hamburg
country: Germany
facility: Bethesda Krankenhaus Bergedorf, Klinik für Innere Medizin
Study officials:
affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
name: Stephan Ehrhardt, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.