Evaluation of the Use of a Probiotic Containing Bifidobacterium Breve PRL2020 in Oral Drops in Preventing Side Effects From Amoxicillin or Amoxicillin/Clavulanic Acid Antibiotic Use

NCT07234448 | Not Yet Recruiting DMC

• 1 other identifier: Brevicillin_PRL2020_Trial
• Study Type: interventional
• Target: 1,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Antibiotic-associated Diarrhea

Outcome Measures

Primary Outcomes (1)

• Incidence of Antibiotic-Associated Diarrhea (AAD)

  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 Outcomes (7)

• Incidence of children with at least one episode of diarrhea

  15 days

• Number of daily defecations

  15 days

• Number of days with diarrhea

  15 days

• Stool consistency

  15 days

• Gastrointestinal and extra-intestinal symptoms

  15 days

Study Arms (2)

Brevicillin® gocce (Bifidobacterium breve PRL2020)

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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)

Interventions

Brevicillin® gocce (Bifidobacterium breve PRL2020) DIETARY_SUPPLEMENT

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.

Brevicillin® gocce (Bifidobacterium breve PRL2020)

Placebo (matching oil drops) OTHER

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.

Placebo

Eligibility Criteria

• Age: 0 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male and female participants aged 0-12 years.
• Undergoing antibiotic therapy with amoxicillin or amoxicillin/clavulanic acid.
• Parent or legal guardian provides written informed consent.

You may not qualify if:

• Use of antibiotic therapy within 4 weeks prior to enrolment.
• Use of other probiotic products or lactic acid bacteria during the study.
• Pre-existing diarrhea within 4 weeks prior to enrolment.
• Chronic inflammatory bowel disease.
• Immunodeficiency.
• Lack of parental or legal guardian consent to participate in the study.

Sponsors & Collaborators

• Liaquat University of Medical & Health Sciences: lead
• University of Urbino "Carlo Bo": collaborator

Related Publications (7)

• Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med. 2002 Jan 31;346(5):334-9. doi: 10.1056/NEJMcp011603. No abstract available.

  PMID: 11821511 BACKGROUND

• Salvo F, Polimeni G, Moretti U, Conforti A, Leone R, Leoni O, Motola D, Dusi G, Caputi AP. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. J Antimicrob Chemother. 2007 Jul;60(1):121-6. doi: 10.1093/jac/dkm111. Epub 2007 Apr 21.

  PMID: 17449881 BACKGROUND

• Caron F, Ducrotte P, Lerebours E, Colin R, Humbert G, Denis P. Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings. Antimicrob Agents Chemother. 1991 Jun;35(6):1085-8. doi: 10.1128/AAC.35.6.1085.

  PMID: 1929247 BACKGROUND

• Yang L, Bajinka O, Jarju PO, Tan Y, Taal AM, Ozdemir G. The varying effects of antibiotics on gut microbiota. AMB Express. 2021 Aug 16;11(1):116. doi: 10.1186/s13568-021-01274-w.

  PMID: 34398323 BACKGROUND

• Mancabelli L, Mancino W, Lugli GA, Argentini C, Longhi G, Milani C, Viappiani A, Anzalone R, Bernasconi S, van Sinderen D, Ventura M, Turroni F. Amoxicillin-Clavulanic Acid Resistance in the Genus Bifidobacterium. Appl Environ Microbiol. 2021 Mar 11;87(7):e03137-20. doi: 10.1128/AEM.03137-20. Print 2021 Mar 11.

  PMID: 33483308 BACKGROUND

• Di Pierro F, Campedelli I, De Marta P, Fracchetti F, Del Casale A, Cavecchia I, Matera M, Cazzaniga M, Bertuccioli A, Guasti L, Zerbinati N. Bifidobacterium breve PRL2020: Antibiotic-Resistant Profile and Genomic Detection of Antibiotic Resistance Determinants. Microorganisms. 2023 Jun 24;11(7):1649. doi: 10.3390/microorganisms11071649.

  PMID: 37512822 BACKGROUND

• Biasucci G, Capra ME, Giudice A, Monopoli D, Stanyevic B, Rotondo R, Mucci A, Neglia C, Campana B, Esposito S. Use of Probiotics During Antibiotic Therapy in Pediatrics: A Cross-Sectional Survey of Italian Primary Care Pediatricians. Antibiotics (Basel). 2025 Jun 4;14(6):577. doi: 10.3390/antibiotics14060577.

  PMID: 40558167 BACKGROUND

Study Officials

• Davide Sisti, PhD

  University of Urbino "Carlo Bo"

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Davide Sisti, PhD

CONTACT

+39-0722-303301; davide.sisti@uniurb.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind design: both participants, care providers, investigators, and outcome assessors are unaware of treatment assignments. The probiotic and placebo products are identical in appearance, packaging, and labeling.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Biochemistry and Experimental Medicine

Model Details: Participants are randomized in a 1:1 ratio to receive either Brevicillin® gocce containing Bifidobacterium breve PRL2020 or a matching placebo, both administered only during the antibiotic treatment period (6-10 days, according to physician prescription). After completion of antibiotic therapy, all participants enter a follow-up period through day 15 without probiotic or placebo administration.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 18, 2025
• Study Start: December 1, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): May 29, 2026
• Last Updated: November 24, 2025

Record last verified: 2025-11