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

This study has been terminated.
(Masked independent interim analysis showed that successful completion of the trial was unlikely. Trial was stopped early in agreement with DSMB.)
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Stephan Ehrhardt, Bernhard Nocht Institute for Tropical Medicine
ClinicalTrials.gov Identifier:
NCT01143272
First received: June 11, 2010
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Antibiotic Treatment
Clostridium Difficile
Diarrhea
Drug: Perenterol® Forte
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea - Randomised, Double-blind, Placebo-controlled Trial

Resource links provided by NLM:


Further study details as provided by Bernhard Nocht Institute for Tropical Medicine:

Primary Outcome Measures:
  • Cumulative incidence of any antibiotic-associated diarrhoea [ Time Frame: 29 months ] [ Designated as safety issue: No ]
    Cumulative incidence of any antibiotic-associated diarrhoea


Secondary Outcome Measures:
  • Cumulative incidence of Clostridium difficile-associated diarrhoea [ Time Frame: 29 months ] [ Designated as safety issue: No ]
  • Cumulative incidence of antibiotic-associated diarrhoea without evidence of Clostridium difficile (toxins) [ Time Frame: 29 months ] [ Designated as safety issue: No ]
  • Cumulative incidence of Clostridium difficile-associated diarrhoea among all antibiotic-associated diarrhoeas [ Time Frame: 29 months ] [ Designated as safety issue: No ]
  • Influence of initial white blood cell count and c-reactive protein on the incidence of antibiotic-associated diarrhoea [ Time Frame: 29 months ] [ Designated as safety issue: No ]
  • Hazard rate of antibiotic-associated diarrhoea and Clostridium difficile-associated diarrhoea [ Time Frame: 29 months ] [ Designated as safety issue: No ]
  • Mean duration of antibiotic-associated diarrhoea and Clostridium difficile-associated diarrhoea [ Time Frame: 29 months ] [ Designated as safety issue: No ]
  • Mean stool frequency in patients with antibiotic-associated diarrhoea and Clostridium difficile-associated diarrhoea [ Time Frame: 29 months ] [ Designated as safety issue: No ]
  • Cumulative incidence of change of initially prescribed antibiotic [ Time Frame: 29 months ] [ Designated as safety issue: No ]

Enrollment: 477
Study Start Date: June 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Saccharomyces boulardii
500 mg Saccharomyces boulardii per day
Drug: Perenterol® Forte
Units: 500 mg per day Route of administration : Oral Use Hard-Capsule
Other Name: Perenterol® Forte
Placebo Comparator: Microcristallin cellulose
Matching capsules containing no active ingredients
Drug: Placebo
Placebo
Other Names:
  • Placebo
  • Microcristallin cellulose
  • Matching capsules containing no active ingredients

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01143272

Locations
Germany
Abteilung Innere Medizin, Bundeswehrkrankenhaus Ulm
Ulm, Baden-Würtemberg, Germany, 89081
Klinik und Poliklinik für Innere Medizin, Abteilung für Tropenmedizin und Infektionskrankheiten, Universitätsklinikum Rostock
Rostock, Mecklenburg-Vorpommern, Germany, 18057
Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, Zentrum für Pneumologie
Rotenburg, Niedersachsen, Germany, 27356
Knappschaftskrankenhaus Bottrop, Medizinische Klinik
Bottrop, Nordrhein-Westfalen, Germany, 46242
Abteilung Akut-Geriatrie, Ev. Krankenhaus Bethanien Iserlohn
Iserlohn, Nordrhein-Westfalen, Germany, 58644
Klinikum Vest GmbH, Behandlungszentrum Paracelsus-Klinik Marl
Marl, Nordrhein-Westfalen, Germany, 45770
I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität Mainz
Mainz, Rheinland-Pfalz, Germany, 55131
Klinikum Saarbrücken
Saarbrücken, Saarland, Germany, 66119
Klinikum St.Georg, Klinik für Infektiologie, Tropenmedizin und Nephrologie
Leipzig, Sachsen, Germany, 04129
Abt. Innere Medizin, Krankenhaus Reinbek, St. Adolf -Stift
Reinbek, Schleswig-Holstein, Germany, 21465
Medizinische Klinik I, Gastroenterologie / Infektiologie / Rheumatologie, Charité-Universitätsmedizin-Berlin, Campus Benjamin Franklin
Berlin, Germany, 12200
Klinikum Bremen Ost, Klinik für Innere Medizin
Bremen, Germany, 28325
Bethesda Krankenhaus Bergedorf, Klinik für Innere Medizin
Hamburg, Germany, 21029
I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Agaplesion Diakonieklinikum Hamburg, Klinik für Innere Medizin
Hamburg, Germany, 20259
Sponsors and Collaborators
Bernhard Nocht Institute for Tropical Medicine
German Federal Ministry of Education and Research
Investigators
Principal Investigator: Stephan Ehrhardt, MD, MPH Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
  More Information

Additional Information:
No publications provided

Responsible Party: Stephan Ehrhardt, Lead investigator, Bernhard Nocht Institute for Tropical Medicine
ClinicalTrials.gov Identifier: NCT01143272     History of Changes
Other Study ID Numbers: BNI-2009-01, 2009-017374-20, ISRCTN01005546, DRKS00000084
Study First Received: June 11, 2010
Last Updated: December 10, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bernhard Nocht Institute for Tropical Medicine:
antibiotic
associated
diarrhoea
saccharomyces boulardii
Antibiotic-associated diarrhoea (AAD)
Clostridium difficile-associated-diarrhoea (CDAD)

Additional relevant MeSH terms:
Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents

ClinicalTrials.gov processed this record on August 27, 2014