Probiotic Bifidobacterium Breve PRL2020 in Oral Drops in Preventing Side Effects From Amoxicillin or Amoxicillin/Clavulanic Acid Antibiotic Use

November 10, 2026 updated by: Dr. Amjad Khan, Liaquat University of Medical & Health Sciences

Assessment of the Impact of an Amoxicillin/Clavulanic Acid-resistant Probiotic on the Reduction of AAD (Antibiotic-Associated Diarrhoea) in Children Treated With Amoxicillin/Clavulanic Acid or Amoxicillin: a Multicentre, Randomised, Placebo-controlled Clinical Trial.

This multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of the probiotic Bifidobacterium breve PRL2020 (Brevicillin® gocce) in preventing gastrointestinal side effects associated with antibiotic therapy using amoxicillin or amoxicillin/clavulanic acid in pediatric patients aged 0-12 years. Participants will be randomized 1:1 to receive either the probiotic supplement or placebo during standard antibiotic treatment for 6-10 days, followed by a post-treatment observation period up to day 15 without probiotic or placebo administration. The primary objective is to assess the reduction in the incidence of antibiotic-associated diarrhea (AAD).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid is widely prescribed in pediatric populations but is frequently associated with gastrointestinal adverse effects, particularly diarrhea. These effects are linked to disruption of the gut microbiota and a reduction in bifidobacterial populations. Bifidobacterium breve PRL2020 is a probiotic strain with demonstrated intrinsic, non-transferable resistance to these antibiotics and has been developed to mitigate antibiotic-induced dysbiosis.

This study is a multicenter, prospective, randomized, double-blind, placebo-controlled, non-profit trial conducted in pediatric centers across Italy. The study aims to evaluate the clinical efficacy and safety of Bifidobacterium breve PRL2020 in reducing the incidence and severity of antibiotic-associated diarrhea (AAD) in children receiving amoxicillin or amoxicillin/clavulanic acid.

A total of 1024 participants will be enrolled. Participants will be randomized 1:1 to receive either Brevicillin® gocce (5 drops 2-3 times daily, containing 5 billion CFU of B. breve PRL2020 per dose) or matching placebo only during antibiotic therapy (6-10 days). After completion of antibiotic treatment, participants will enter a follow-up period until day 15 without probiotic or placebo administration.

The primary outcome is the incidence of AAD, defined as ≥3 diarrheal episodes in one day during antibiotic treatment (Bristol Stool Scale 5-7).

Secondary outcomes include the incidence and duration of diarrhea, daily bowel movements, stool consistency, gastrointestinal and extra-intestinal symptoms (such as nausea, vomiting, abdominal pain), treatment compliance, and adverse events.

Study Type

Interventional

Enrollment (Estimated)

1024

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Alessandria, Italy, 15121
        • GROSSO CATERINA Studio medico - Spalto Marengo 92
        • Contact:
      • Alessandria, Italy, 15121
        • VALARAUDI PIERA Studio medico - Via Galimberti 25
        • Contact:
      • Busto Arsizio, Italy, 21052
        • MORGANTI GIANFRANCO Studio medico - Via Rossini Gioachino 9
        • Contact:
      • Frosinone, Italy, 03100
        • MARIANI PAOLO Studio medico - VIA AMERICA LATINA 135
        • Contact:
      • Genova, Italy, 16129
        • POGGI ELENA Studio medico - Via Montevideo 8
        • Contact:
      • Messina, Italy, 98123
        • BARBALACE ANDREA Studio medico - Via Nino Bixio 76
        • Contact:
      • Messina, Italy, 98123
        • INFERRERA RAMONA Studio medico - Via Trieste 19
        • Contact:
      • Roma, Italy, 00156
        • PACCHIAROTTI ALESSIA Studio medico - VIA FIUMINATA 4
        • Contact:
      • Torino, Italy, 10137
        • ROVELLI ILARIA Studio medico - Via Baltimora 86
        • Contact:
      • Varese, Italy, 21100
        • COLLI GIOVANNI studio medico privato - via Caracciolo 54
        • Contact:
    • Catanzaro
      • Lamezia Terme, Catanzaro, Italy, 88046
        • NERO ANNA MARIA Centro Salute Galattica - Via Giovanni Gronchi, 1
        • Contact:
    • Chieti
      • Casoli, Chieti, Italy, 66043
        • ANTONELLI LUCIETTA Studio medico - Vico Montaniera 27
        • Contact:
    • Como
      • Cantù, Como, Italy, 22063
        • OMETTO MARIANGELA studio pediatrico associato - via Al Monte 4
        • Contact:
    • Frosinone
      • Anagni, Frosinone, Italy, 03012
        • D'AVERSA IRENE Studio medico - VIALE REGINA MARGHERITA 7
        • Contact:
      • Anagni, Frosinone, Italy, 03012
        • NOTO CRISTIAN Studio medico - VIA TARTARALTA DI SOTTO 25
        • Contact:
    • Padova
      • Piazzola sul Brenta, Padova, Italy, 35016
        • NARDINI FLAVIA studio medico - Via Portico della Tessitura 3/1
        • Contact:
    • Palermo
      • Bagheria, Palermo, Italy
        • MANCUSO GIUSEPPINA Studio medico - Via De Spuches 14
        • Contact:
    • Perugia
      • Bastia umbra, Perugia, Italy, 06083
        • RASTELLI STEFANIA studio medico - Via Foligno 23
        • Contact:
      • Foligno, Perugia, Italy, 06034
        • CAMPUS MARIA GIULIA studio medico - Via Aspromonte SNC
        • Contact:
    • Venezia
      • Mira, Venezia, Italy, 30034
        • SATARIANO IRENE studio medico - Largo S.Luca 2
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients of either sex
  • Age ≤ 12 years
  • Requirement to undergo antibiotic treatment with amoxicillin or amoxicillin/clavulanic acid

Exclusion Criteria:

  • Use of antibiotic therapy in the 4 weeks prior to enrolment in the study.
  • Use of other probiotic products or products containing lactic acid bacteria during the study period.
  • Presence of pre-existing diarrhoea in the 4 weeks prior to enrolment.
  • Presence of chronic inflammatory bowel disease.
  • Presence of immunodeficiency.
  • Failure to obtain informed consent from the parent or legal guardian for participation in the study.
  • Known allergy to the excipients in the formulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Brevicillin® gocce (Bifidobacterium breve PRL2020)

Participants will receive Brevicillin® gocce, a probiotic food supplement containing Bifidobacterium breve PRL2020 (LMG S-32458), alongside standard antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid.

Dosage and administration: 5 drops, 2-3 times per day (depending on antibiotic dosing schedule), administered during the antibiotic treatment period (6-10 days). After completion of antibiotic therapy, participants will enter a follow-up period until day 15 without probiotic administration.
Dietary supplement: Brevicillin® gocce (Bifidobacterium breve PRL2020)

Brevicillin® gocce is a probiotic dietary supplement in oily drops containing the bacterial strain Bifidobacterium breve PRL2020 (LMG S-32458). Each 5-drop dose contains approximately 5 billion live cells. The supplement is administered orally 2-3 times per day, in parallel with antibiotic therapy (amoxicillin or amoxicillin/clavulanic acid), for 6-10 days only (during the antibiotic course).

After completion of antibiotic therapy, participants enter a follow-up period until day 15 without probiotic administration.

The product is manufactured by PharmExtracta S.p.A., Pontenure, Italy.
Placebo Comparator: Placebo

Participants will receive a placebo formulation matched in appearance, packaging, and dosing schedule to Brevicillin® gocce, administered alongside standard antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid.

The placebo will be given at the same frequency (5 drops, 2-3 times per day) and duration as the experimental product during the antibiotic treatment period (6-10 days). After antibiotic completion, participants will enter a follow-up period until day 15 without placebo administration.
Other: Placebo (matching oil drops)

The placebo is a formulation identical in appearance, packaging, and administration schedule to Brevicillin® gocce but without the Bifidobacterium breve PRL2020 strain. It is administered orally 2-3 times per day only during the antibiotic treatment period (6-10 days).

After antibiotic completion, participants enter a follow-up period until day 15 without placebo administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Antibiotic-Associated Diarrhea (AAD)
Time Frame: 15 days

Evaluation of the efficacy of Bifidobacterium breve PRL2020 (Brevicillin® gocce) in reducing the incidence of antibiotic-associated diarrhea (AAD), defined as ≥3 diarrheal episodes within one day of antibiotic treatment, with stool consistency corresponding to types 5-7 on the Bristol Stool Scale. Data will be collected through a daily diary completed by the parent or legal guardian.
15 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of children with at least one episode of diarrhea
Time Frame: 15 days

Number of participants experiencing at least one episode of diarrhea during the study period, as recorded in the daily diary.
15 days
Number of daily defecations
Time Frame: 15 days

Average number of daily bowel movements recorded by the parent or guardian during the study period, using the child's daily diary.
15 days
Number of days with diarrhea
Time Frame: 15 days

Total number of days in which diarrhea occurs during the observation period, recorded by the parent or guardian.
15 days
Stool consistency
Time Frame: 15 days

Assessment of stool consistency using the Bristol Stool Scale (BSS) to evaluate changes in bowel habits during and after antibiotic treatment.
15 days
Abdominal pain During and After Antibiotic Treatment
Time Frame: 15 days

Assessment of abdominal pain related to antibiotic use, as recorded in daily diary entries completed by the parent or guardian.
15 days
Nausea During and After Antibiotic Treatment
Time Frame: 15 days

Assessment of nausea related to antibiotic use, as recorded in daily diary entries completed by the parent or guardian.
15 days
Vomiting During and After Antibiotic Treatment
Time Frame: 15 days

Assessment of vomiting related to antibiotic use, as recorded in daily diary entries completed by the parent or guardian.
15 days
Treatment compliance
Time Frame: 15 days

Assessment of adherence to the probiotic or placebo regimen, graded by the pediatrician on a scale from "poor" to "excellent" at the end of the study period.
15 days
Adverse events
Time Frame: 15 days

Documentation and evaluation of any adverse events reported during treatment and follow-up, as recorded in the child's daily diary and verified by the study physician.
15 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Liaquat University of Medical & Health Sciences

Collaborators

University of Urbino "Carlo Bo"

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 16, 2026

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

November 6, 2026

First Submitted That Met QC Criteria

November 10, 2026

First Posted (Actual)

November 13, 2026

Study Record Updates

Last Update Posted (Actual)

November 13, 2026

Last Update Submitted That Met QC Criteria

November 10, 2026

Last Verified

November 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

  • 188_2ottobre2026_DROPS AAD_Sis

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe