NCT02765217

Brief Summary

Recent studies showed that intestinal microbiota consist more than thousand bacteria, and these microorganisms play the role as balance and continuity of the anatomical and functional integrity gastrointestinal tract. Chronic diseases, nutritional factors, lifestyle factors and medications including antibiotics changes the host microbiota in short or long-term period. Antibiotics are the most commonly used drugs in pediatrics routine practice. Although frequency and severity of side effects alter the choice of drug, mild complications may be taken into consideration for treatment by a physician in the profit and loss balance. Our study group (PROBAGE Working Group) have been recently showed that Lactobacillus reuteri DSM 17938 reduced the duration of diarrhea in children with acute infectious diarrhea, and are safe and well-tolerated. In this study the investigators aim to evaluate the potential effect of Lactobacillus reuteri DSM 17938 on the prevention of antibiotic associated diarrhea in children.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,325

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jun 2017

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 2, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 6, 2016

Completed
1.1 years until next milestone

Study Start

First participant enrolled

June 1, 2017

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2020

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

February 15, 2021

Status Verified

February 1, 2021

Enrollment Period

3.1 years

First QC Date

May 2, 2016

Last Update Submit

February 11, 2021

Conditions

Keywords

Antibiotic associated diarrheaChildrenPreventionLactobacillus reuteri DSM 17938Probiotic

Outcome Measures

Primary Outcomes (1)

  • Incidence of antibiotic associated diarrhea

    The frequency and consistency of the stools were recorded daily according to Bristol score; a score \<5 is described as normalization of stool and score equal or above 5 defined as diarrhea. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug, Graded According to NCI CTCAE Version 3.0

    8 weeks time period after 1st day of antibiotic use

Secondary Outcomes (4)

  • Incidence of antibiotic associated diarrhea during antibiotic treatment

    10-14 days (depends on the antibiotic treatment)

  • Incidence of antibiotic associated diarrhea after antibiotic treatment

    From 11-15th days of intervention to 56 days

  • Evaluation of antibiotic-associated diarrhea in patients who developed diarrhea severity

    56 days

  • The frequency of other gastrointestinal symptoms other than diarrhea during the study (will be evaluated using the Gastrointestinal Symptom Rating Score)

    56 days

Study Arms (4)

Study group 1

EXPERIMENTAL

Amoxicilline-clavulanic acid (50-90 mg/kg/day, twice daily) and Lactobacillus reuteri DSM 17938 (5 drops per day, same time with the first dose of antibiotics). Study Group 1a will received L. reuteri for 10-14 days. Study Group 1b will received L. reuteri for 21 days.

Drug: Lactobacillus reuteri DSM 17938Drug: Amoxicillin-Clavulanic Acid

Study group 2

PLACEBO COMPARATOR

Amoxicillin-clavulanic acid (50-90 mg / kg / day) and placebo ( 5 drops per day, same time with the antibiotics) Study Group 2a will received placebo for 10-14 days. Study Group 2b will received placebo for 21 days.

Drug: PlaceboDrug: Amoxicillin-Clavulanic Acid

Study group 3

EXPERIMENTAL

Amoxicilline-clavulanic acid (50-90 mg/kg/day, twice daily) and Lactobacillus reuteri DSM 17938 (2 x 5 drops per day) Study Group 3a will received L. reuteri for 10-14 days. Study Group 3b will received L. reuteri for 21 days.

Drug: Lactobacillus reuteri DSM 17938Drug: Amoxicillin-Clavulanic Acid

Study group 4

PLACEBO COMPARATOR

Amoxicillin-clavulanic acid (50-90 mg / kg / day) and placebo ( 2 x 5 drops per day, same time with the antibiotics) Study Group 4a will received placebo for 10-14 days. Study Group 4b will received placebo for 21 days.

Drug: PlaceboDrug: Amoxicillin-Clavulanic Acid

Interventions

Comparison the effects of Lactobacillus reuteri DSM 17938 and placebo for prevention of antibiotic associated diarrhea and also plan to compare the duration of treatment for on efficacy.

Also known as: BioGaia
Study group 1Study group 3

Comparison the effects of Lactobacillus reuteri DSM 17938 and placebo for prevention of antibiotic associated diarrhea and also plan to compare the duration of treatment for on

Study group 2Study group 4

All study patients will received amoxicillin-clavulanic acid at the dose of 50-90 mg/kg/day.

Also known as: Co-amoxilav
Study group 1Study group 2Study group 3Study group 4

Eligibility Criteria

Age6 Months - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Children receiving amoxicilline-clavulanic acid (50-90 mg/kg/day, twice daily) due to acute otitis media or acute sinusitis

You may not qualify if:

  • Receiving antibiotic and/or probiotic, 8 weeks before the study
  • Chronic gastrointestinal system disorders
  • Congenital anomalies
  • Chronic diseases
  • Chemotherapy and radiotherapy
  • Pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sisli Etfal Training and Research Hospital,

Istanbul, 34000, Turkey (Türkiye)

Location

Related Publications (1)

  • Dinleyici EC, Ozen M, Guven S, Dalgic N, Karbuz A, Sutcu M, Turel O, Oz FN, Kirli U, Yasar Durmus S, Yazar AS, Cakin ZE, Vandenplas Y, Kara A. Effect of Limosilactobacillus reuteri DSM17938 to prevent antibiotic-associated diarrhea in children: prospective, multi-center, randomized, placebo-controlled clinical trial (PEARL Study). Eur J Pediatr. 2025 Jun 9;184(7):408. doi: 10.1007/s00431-025-06249-8.

MeSH Terms

Interventions

Amoxicillin-Potassium Clavulanate Combination

Intervention Hierarchy (Ancestors)

Clavulanic AcidClavulanic Acidsbeta-LactamsLactamsAmidesOrganic ChemicalsAmoxicillinAmpicillinPenicillin GPenicillinsSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor in Pediatrics

Study Record Dates

First Submitted

May 2, 2016

First Posted

May 6, 2016

Study Start

June 1, 2017

Primary Completion

July 1, 2020

Study Completion

December 1, 2020

Last Updated

February 15, 2021

Record last verified: 2021-02

Locations