Lactobacillus Reuteri DSM 17938 in the Prevention of Antibiotic-associated Diarrhea in Children: Protocol of a Randomized Controlled Trial

• ClinicalTrials.gov Identifier: NCT02871908
• Recruitment Status: Completed
• First Posted: August 18, 2016
• Last Update Posted: March 20, 2018
• Sponsor: Medical University of Warsaw
• Information provided by (Responsible Party): Hanna Szajewska, Medical University of Warsaw

Tracking Information

• First Submitted Date: August 16, 2016
• First Posted Date: August 18, 2016
• Last Update Posted Date: March 20, 2018
• Study Start Date: December 2016
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 19, 2016)

frequencies of diarrhea and antibiotic associated diarrhea [ Time Frame: during antibiotic treatment, an average of 10 days and 7 days of follow up ]

Three different definitions of diarrhea will be used, as the definitions of diarrhea/AAD in published studies vary. These will include diarrhea defined as: (a) ≥3 loose or watery stools per day for a minimum of 48 hours during antibiotic treatment; (b) ≥3 loose or watery stools per day for a minimum of 24 hours during antibiotic treatment, and (c) ≥2 loose or watery stools per day for a minimum of 24 hours during antibiotic treatment. AAD will be diagnosed in cases of diarrhea, defined clinically as above, caused by C. difficile or for otherwise unexplained diarrhea (i.e., negative laboratory stool tests for infectious agents). In all cases, loose or watery stools will correspond to scores of 5 to 7 on the BSF scale or A-consistency on the AISS.

Original Primary Outcome Measures (submitted: August 17, 2016)

frequencies of diarrhea and antibiotic associated diarrhea [ Time Frame: during antibiotic treatment and 7 days of follow up ]

Three different definitions of diarrhea will be used, as the definitions of diarrhea/AAD in published studies vary. These will include diarrhea defined as: (a) ≥3 loose or watery stools per day for a minimum of 48 hours during antibiotic treatment; (b) ≥3 loose or watery stools per day for a minimum of 24 hours during antibiotic treatment, and (c) ≥2 loose or watery stools per day for a minimum of 24 hours during antibiotic treatment. AAD will be diagnosed in cases of diarrhea, defined clinically as above, caused by C. difficile or for otherwise unexplained diarrhea (i.e., negative laboratory stool tests for infectious agents). In all cases, loose or watery stools will correspond to scores of 5 to 7 on the BSF scale or A-consistency on the AISS.

Current Secondary Outcome Measures (submitted: August 19, 2016)

• infectious diarrhea [ Time Frame: during antibiotic treatment, an average of 10 days and 7 days of follow up ]
  rotavirus, adenovirus, norovirus, Salmonella, Shigella, Campylobacter, Yersinia and C. difficile
• the need for discontinuation of the antibiotic treatment [ Time Frame: during antibiotic treatment, an average of 10 days ]
• the need for hospitalization to manage the diarrhea (in outpatients) [ Time Frame: during antibiotic treatment, an average of 10 days and 7 days of follow up ]
• the need for intravenous rehydration in any of the study groups [ Time Frame: during antibiotic treatment, an average of 10 days and 7 days of follow up ]
• adverse events [ Time Frame: during antibiotic treatment, an average of 10 days and 7 days of follow up ]

Original Secondary Outcome Measures (submitted: August 17, 2016)

• infectious diarrhea [ Time Frame: during antibiotic treatment and 7 days of follow up ]
  rotavirus, adenovirus, norovirus, Salmonella, Shigella, Campylobacter, Yersinia and C. difficile
• the need for discontinuation of the antibiotic treatment [ Time Frame: during antibiotic treatment ]
• the need for hospitalization to manage the diarrhea (in outpatients) [ Time Frame: during antibiotic treatment and 7 days of follow up ]
• the need for intravenous rehydration in any of the study groups [ Time Frame: during antibiotic treatment and 7 days of follow up ]
• adverse events [ Time Frame: during antibiotic treatment and 7 days of follow up ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lactobacillus Reuteri DSM 17938 in the Prevention of Antibiotic-associated Diarrhea in Children: Protocol of a Randomized Controlled Trial
• Official Title: Lactobacillus Reuteri DSM 17938 in the Prevention of Antibiotic-associated Diarrhea in Children: Protocol of a Randomized Controlled Trial
• Brief Summary: The aim of this study is to assess the effect of Lactobacillus reuteri DSM 17938 administration for the prevention of diarrhea and AAD in children.

Detailed Description

Introduction:

Addition of some probiotics appears to reduce the risk of antibiotic-associated diarrhea (AAD). Effects of probiotics are strain specific, thus the efficacy and safety of each probiotic strain should be established separately. We aim to assess the effect of Lactobacillus reuteri DSM 17938 administration for the prevention of diarrhea and AAD in children.

Methods and analysis:

A total of 250 children younger than 18 years treated with antibiotics will be enrolled into a double-blind, randomized placebo-controlled trial in which they will additionally receive L reuteri DSM 17938 at a dose 2 x 10^8 colony-forming units or an identically appearing placebo, orally, twice daily, for the entire duration of antibiotic treatment. The primary outcome measures will be the frequency of diarrhea and AAD. Diarrhea will be defined according to one of 3 definitions: (a) ≥3 loose or watery stools per day for a minimum of 48 hours during antibiotic treatment; (b) ≥3 loose or watery stools per day for a minimum of 24 hours during antibiotic treatment; (c) ≥2 loose or watery stools per day for a minimum of 24 hours during antibiotic treatment. AAD will be diagnosed in cases of diarrhea, defined clinically as above, caused by C. difficile or for otherwise unexplained diarrhea (i.e. negative laboratory stool tests for infectious agents).

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Diarrhea
• Antibiotic Associated Diarrhea

Intervention

• Drug: Lactobacillus reuteri DSM 17938
  Lactobacillus reuteri DSM 17938 twice daily 2 x 10^8
• Drug: Placebo
  Placebo

Study Arms

• Experimental: L reuteri DSM 17938
  L reuteri DSM 17938 2 x 10^8 twice daily
  Intervention: Drug: Lactobacillus reuteri DSM 17938
• Placebo Comparator: Controls
  Identically appearing placebo twice daily
  Intervention: Drug: Placebo

• Publications *: Kołodziej M, Szajewska H. Lactobacillus reuteri DSM 17938 in the prevention of antibiotic-associated diarrhoea in children: protocol of a randomised controlled trial. BMJ Open. 2017 Jan 5;7(1):e013928. doi: 10.1136/bmjopen-2016-013928.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2016): 250
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 2018
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• age younger than 18 years;
• oral or intravenous antibiotic therapy which started within 24 hours of enrollment;
• signed informed consent.

Exclusion Criteria:

• pre-existing acute or chronic diarrhea,
• history of chronic gastrointestinal disease (e.g., inflammatory bowel disease, cystic fibrosis, celiac disease, food allergy) or other severe chronic disease (e.g., neoplastic diseases), immunodeficiency,
• use of probiotics within 2 weeks prior to enrollment,
• use of antibiotics within 4 weeks prior to enrollment,
• prematurity, and exclusive breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Poland

Administrative Information

• NCT Number: NCT02871908
• Other Study ID Numbers: 12/08/2016
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Hanna Szajewska, Medical University of Warsaw
• Study Sponsor: Medical University of Warsaw
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Medical University of Warsaw
• Verification Date: March 2018