Effect of Probiotic Formula on Reducing the Risk for Antibiotic-associated Diarrhoea

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01596829
Recruitment Status : Terminated (low incidence)
First Posted : May 11, 2012
Last Update Posted : January 22, 2016
Information provided by (Responsible Party):

Brief Summary:
Antibiotic treatment disturbs the balance of the intestinal microbiota and predisposes to antibiotic associated diarrhea. Previous studies have shown that the risk of developing diarrhea during a course of antibiotics may be reduced by simultaneous consumption of probiotics. The aim of the present study is to assess the effect of a probiotic formula containing four strains on reducing the risk of antibiotic associated diarrhea.

Condition or disease Intervention/treatment Phase
Antibiotic-associated Diarrhoea Dietary Supplement: Probiotic Dietary Supplement: Placebo Phase 2 Phase 3

Detailed Description:
The aim of the study is to assess the effect of a probiotic formula on reducing the risk of antibiotic-associated diarrhea (AAD). The study will be conducted as a two-arm, parallel groups, placebo-controlled, double-blind, randomized clinical trial, stratified by age, gender and number of days on antibiotics. The duration of patient participation in the study will be up to 7 weeks (up to 3 weeks supplementation, 4 weeks follow-up). The overall duration of the study is expected to be approximately 8 months. Adult males and females that are prescribed antibiotic therapy for minimum of 3 and a maximum of 14 days will be included in the study. The incidence of AAD will be evaluated as the primary end-point. The stool from patients presenting diarrhea will be tested for the presence of Clostridium difficile and if negative for C. difficile, also for the presence of other common pathogens causing diarrhea. The overall microbiota will be analyzed from fecal samples taken regularly during each phase of the study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 258 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Effect of Probiotic Formula on Reducing the Risk for Antibiotic-associated Diarrhoea
Study Start Date : December 2012
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics Diarrhea
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Probiotic
Probiotic consumption during and after course of antibiotic
Dietary Supplement: Probiotic
Probiotic formula, 10 billion CFU in total once a day for up to 3 weeks
Other Name: Howaru Restore
Placebo Comparator: Placebo
Placebo consumed during and after course of antibiotic
Dietary Supplement: Placebo
A capsule with microcrystalline cellulose matching the appearance and taste of the active comparator
Other Name: Microcrystalline cellulose as placebo

Primary Outcome Measures :
  1. Incidence of AAD [ Time Frame: Up to 21 days ]
    Incidence of diarrhoea defined as three or more loose or watery stools per a 24 h period.

Secondary Outcome Measures :
  1. Duration of diarrhoea [ Time Frame: Up to 21 days ]
    Number of continuous days of diarrhoea

  2. Fecal microbiota [ Time Frame: Up to 21 days ]
    Analysis of overall microbiota from all samples and of causative diarrhoeal agent from samples taken during diarrhoeal episode

  3. Safety profile [ Time Frame: Up to 21 days ]
    Evaluation of serious and non-serious adverse events

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males and females aged 18-65 years.
  2. Patients will be initiating antibiotic therapy.
  3. The antibiotic therapy consists of one of the following: broad spectrum penicillins, cephalosporins, doxycycline, clarithromycin, ciprofloxacin or isoxazolyl penicillin.
  4. The antibiotic therapy is expected to be 3 to 14 days in duration.
  5. Obtained his/her informed consent after verbal and written information.
  6. Have a high probability for compliance with and completion of the study.
  7. Patients having a telephone available.
  8. Body Mass Index between 19 and 30.

Exclusion Criteria:

  1. Participation in a clinical trial with an investigational product or drug within the 60 days prior to screening.
  2. Likeliness to be noncompliant with the protocol, or to be unsuitable to the study by the investigator for any reason.
  3. Pregnant or breastfeeding women; women planning to become pregnant during the study months.
  4. Presence of active diarrhea (3 or more loose or watery stools per 24 hour period).
  5. Daily consumption of probiotics, fermented milk and/or yogurt with probiotics.
  6. Known to have a previous reaction, including anaphylaxis, to any substance in composition of the study product (i.e. on-medicinal ingredients: Cellulose, hypromellose, magnesium stearate (vegetable source), ascorbic acid, Colloidal silicon dioxide).
  7. Presence of an active, non-controlled intestinal disease such as Crohn's Disease or ulcerative colitis.
  8. Regular use of proton pump inhibitors.
  9. Bowel surgery, artificial heart valve, history of rheumatic heart disease or infective endocarditis.
  10. A previous documented C. difficile infection < 3 months prior to study initiation.
  11. Immunosuppressive therapy or any health condition causing immunosuppression (including haematological malignancies, AIDS).
  12. Ongoing or recent use of antibiotic therapy in the 3 months prior to the study product first administration.
  13. Planned administration of antibiotics other than broad spectrum penicillins, cephalosporins, doxycycline, ciprofloxacin or isoxazolyl penicillin for the treatment of an infection.
  14. History of drug or alcohol abuse.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01596829

Tampere, Finland
Sponsors and Collaborators
Principal Investigator: Toivo Piippo, MD Koskiklinikka Tampereen Lääkärikeskus Oy
Study Chair: Anneli Tarpila, PhD Danisco

Responsible Party: Danisco Identifier: NCT01596829     History of Changes
Other Study ID Numbers: AAD-EU2012
2012-001542-18 ( EudraCT Number )
First Posted: May 11, 2012    Key Record Dates
Last Update Posted: January 22, 2016
Last Verified: December 2014
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Terminated prematurely.

Keywords provided by Danisco:
antibiotic-associated diarrhoea
faecal microbiota

Additional relevant MeSH terms:
Signs and Symptoms, Digestive
Signs and Symptoms
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents