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

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.

Study Overview

• Status: Completed
• Conditions: Diarrhea; Antibiotic Associated Diarrhea
• Intervention / Treatment: Drug: Placebo; Drug: Lactobacillus reuteri DSM 17938

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
• Enrollment (Actual): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland, 02-091
    • Department of Paediatrics, The Medical University of Warsaw, Poland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L reuteri DSM 17938; L reuteri DSM 17938 2 x 10^8 twice daily	Drug: Lactobacillus reuteri DSM 17938; Lactobacillus reuteri DSM 17938 twice daily 2 x 10^8
Placebo Comparator: Controls; Identically appearing placebo twice daily	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequencies of diarrhea and antibiotic associated diarrhea	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.	during antibiotic treatment, an average of 10 days and 7 days of follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
infectious diarrhea	rotavirus, adenovirus, norovirus, Salmonella, Shigella, Campylobacter, Yersinia and C. difficile	during antibiotic treatment, an average of 10 days and 7 days of follow up
the need for discontinuation of the antibiotic treatment		during antibiotic treatment, an average of 10 days
the need for hospitalization to manage the diarrhea (in outpatients)		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		during antibiotic treatment, an average of 10 days and 7 days of follow up
adverse events		during antibiotic treatment, an average of 10 days and 7 days of follow up

Collaborators and Investigators

• Sponsor: Medical University of Warsaw

Publications and helpful links

General Publications

• Kolodziej 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 17, 2016
• First Posted (Estimate): August 18, 2016

Study Record Updates

• Last Update Posted (Actual): March 20, 2018
• Last Update Submitted That Met QC Criteria: March 18, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: 12/08/2016