Probiotic Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea

NCT ID: NCT01143272

Last Updated: 2016-07-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 477 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2012-10-31

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.

Conditions

Antibiotic-associated Diarrhea; Clostridium Difficile; Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Saccharomyces boulardii

Intervention Type: DRUG

Units: 500 mg per day Route of administration : Oral Use Hard-Capsule

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Saccharomyces boulardii

Units: 500 mg per day Route of administration : Oral Use Hard-Capsule

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Perenterol® Forte; Microcristallin cellulose; Matching capsules containing no active ingredients

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Bernhard Nocht Institute for Tropical Medicine

OTHER_GOV

Sponsor Role: lead

Responsible Party

Stephan Ehrhardt

Lead investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephan Ehrhardt, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany

Locations

Abteilung Innere Medizin, Bundeswehrkrankenhaus Ulm

Ulm, Baden-Würtemberg, Germany

Klinikum Bremen Ost, Klinik für Innere Medizin

Bremen, City state Bremen, Germany

I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf

Hamburg, City state of Hamburg, Germany

Agaplesion Diakonieklinikum Hamburg, Klinik für Innere Medizin

Hamburg, City state of Hamburg, Germany

Bethesda Krankenhaus Bergedorf, Klinik für Innere Medizin

Hamburg, City state of Hamburg, Germany

Diakoniekrankenhaus Rotenburg (Wümme) gGmbH, Zentrum für Pneumologie

Rotenburg (Wümme), Lower Saxony, Germany

Klinik und Poliklinik für Innere Medizin, Abteilung für Tropenmedizin und Infektionskrankheiten, Universitätsklinikum Rostock

Rostock, Mecklenburg-Vorpommern, Germany

Knappschaftskrankenhaus Bottrop, Medizinische Klinik

Bottrop, North Rhine-Westphalia, Germany

Abteilung Akut-Geriatrie, Ev. Krankenhaus Bethanien Iserlohn

Iserlohn, North Rhine-Westphalia, Germany

Klinikum Vest GmbH, Behandlungszentrum Paracelsus-Klinik Marl

Marl, North Rhine-Westphalia, Germany

I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, Germany

Klinikum Saarbrücken

Saarbrücken, Saarland, Germany

Klinikum St.Georg, Klinik für Infektiologie, Tropenmedizin und Nephrologie

Leipzig, Saxony, Germany

Abt. Innere Medizin, Krankenhaus Reinbek, St. Adolf -Stift

Reinbek, Schleswig-Holstein, Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 26973849 (View on PubMed)

Related Links

http://www.bni-hamburg.de

Sponsor website

Other Identifiers

2009-017374-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN01005546

Identifier Type: REGISTRY

Identifier Source: secondary_id

DRKS00000084

Identifier Type: REGISTRY

Identifier Source: secondary_id

BNI-2009-01

Identifier Type: -

Identifier Source: org_study_id