Probiotic Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Saccharomyces Boulardii for the Prevention of Antibiotic-associated Diarrhoea - Randomised, Double-blind, Placebo-controlled Trial

Conditions
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Antibiotic-associated Diarrhea, Clostridium Difficile, Diarrhea

Intervention / Treatment
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* Drug: Saccharomyces boulardii
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiotic, associated, diarrhoea, saccharomyces boulardii, Antibiotic-associated diarrhoea (AAD), Clostridium difficile-associated-diarrhoea (CDAD)