Probiotic Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea (SacBo)

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.

Study Overview

• Status: Terminated
• Conditions: Diarrhea; Antibiotic-associated Diarrhea; Clostridium Difficile
• Intervention / Treatment: Drug: Placebo; Drug: Saccharomyces boulardii

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 Type: Interventional
• Enrollment (Actual): 477
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bremen, Germany, 28325
    • Klinikum Bremen Ost, Klinik für Innere Medizin
  • Hamburg, Germany, 20246
    • I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
  • Hamburg, Germany, 20259
    • Agaplesion Diakonieklinikum Hamburg, Klinik für Innere Medizin
  • Hamburg, Germany, 21029
    • Bethesda Krankenhaus Bergedorf, Klinik für Innere Medizin
  • Baden-Würtemberg
    • Ulm, Baden-Würtemberg, Germany, 89081
      • Abteilung Innere Medizin, Bundeswehrkrankenhaus Ulm
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18057
      • Klinik und Poliklinik für Innere Medizin, Abteilung für Tropenmedizin und Infektionskrankheiten, Universitätsklinikum Rostock
  • Niedersachsen
    • Rotenburg, Niedersachsen, Germany, 27356
      • Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, Zentrum für Pneumologie
  • Nordrhein-Westfalen
    • Bottrop, Nordrhein-Westfalen, Germany, 46242
      • Knappschaftskrankenhaus Bottrop, Medizinische Klinik
    • Iserlohn, Nordrhein-Westfalen, Germany, 58644
      • Abteilung Akut-Geriatrie, Ev. Krankenhaus Bethanien Iserlohn
    • Marl, Nordrhein-Westfalen, Germany, 45770
      • Klinikum Vest GmbH, Behandlungszentrum Paracelsus-Klinik Marl
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität Mainz
  • Saarland
    • Saarbrücken, Saarland, Germany, 66119
      • Klinikum Saarbrücken
  • Sachsen
    • Leipzig, Sachsen, Germany, 04129
      • Klinikum St.Georg, Klinik für Infektiologie, Tropenmedizin und Nephrologie
  • Schleswig-Holstein
    • Reinbek, Schleswig-Holstein, Germany, 21465
      • Abt. Innere Medizin, Krankenhaus Reinbek, St. Adolf -Stift

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: Saccharomyces boulardii; Units: 500 mg per day Route of administration : Oral Use Hard-Capsule; Other Names: Perenterol® Forte
Placebo Comparator: 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	Drug: Placebo; Placebo; Other Names: Microcristallin cellulose; Matching capsules containing no active ingredients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total Number of Antibiotic-associated Diarrhea Episodes	29 months

Secondary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: Bernhard Nocht Institute for Tropical Medicine
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Principal Investigator: Stephan Ehrhardt, MD, MPH, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany

Publications and helpful links

General 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.

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: June 11, 2010
• First Submitted That Met QC Criteria: June 11, 2010
• First Posted (Estimate): June 14, 2010

Study Record Updates

• Last Update Posted (Estimate): July 18, 2016
• Last Update Submitted That Met QC Criteria: June 7, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: antibiotic; diarrhoea; associated; saccharomyces boulardii; Antibiotic-associated diarrhoea (AAD); Clostridium difficile-associated-diarrhoea (CDAD)
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: BNI-2009-01; 2009-017374-20 (EudraCT Number); ISRCTN01005546 (Registry Identifier: ISRCTN, http://www.controlled-trials.com/ISRCTN01005546); DRKS00000084 (Registry Identifier: Deutsches Register Klinischer Studien)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided