Clinical trial NCT01596829: Effect of Probiotic Formula on Reducing the Risk for Antibiotic-associated Diarrhoea
Official title: Effect of Probiotic Formula on Reducing the Risk for Antibiotic-associated Diarrhoea
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Antibiotic-associated Diarrhoea
Keywords: antibiotic
probiotic
antibiotic-associated diarrhoea
faecal microbiota
Lead sponsor: Danisco
Sponsor class: INDUSTRY
First posted: 2012-05-11
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of AAD
timeFrame: Up to 21 days
Secondary outcomes:
measure: Duration of diarrhoea
timeFrame: Up to 21 days
measure: Fecal microbiota
timeFrame: Up to 21 days
measure: Safety profile
timeFrame: Up to 21 days
Other outcomes:
Locations:
city: Tampere
country: Finland
facility: Koskiklinikka
Study officials:
affiliation: Koskiklinikka Tampereen Lääkärikeskus Oy
name: Toivo Piippo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Danisco
name: Anneli Tarpila, PhD
role: STUDY_CHAIR
References:
citation: Forssten SD, Yeung N, Ouwehand AC. Fecal Recovery of Probiotics Administered as a Multi-Strain Formulation during Antibiotic Treatment. Biomedicines. 2020 Apr 9;8(4):83. doi: 10.3390/biomedicines8040083.