Antibiotic-associated Diarrhea
Conditions
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).
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 1100 participants (550 per group) 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.
Interventions
DIETARY_SUPPLEMENTBrevicillin® 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.
OTHERPlacebo (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.
Sponsors
Liaquat University of Medical & Health Sciences
University of Urbino "Carlo Bo"
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
0 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Antibiotic-Associated Diarrhea (AAD) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of children with at least one episode of diarrhea | 15 days | Number of participants experiencing at least one episode of diarrhea during the study period, as recorded in the daily diary. |
| Number of daily defecations | 15 days | Average number of daily bowel movements recorded by the parent or guardian during the study period, using the child's daily diary. |
| Number of days with diarrhea | 15 days | Total number of days in which diarrhea occurs during the observation period, recorded by the parent or guardian. |
| Stool consistency | 15 days | Assessment of stool consistency using the Bristol Stool Scale (BSS) to evaluate changes in bowel habits during and after antibiotic treatment. |
| Gastrointestinal and extra-intestinal symptoms | 15 days | Evaluation of symptoms related to antibiotic use, including abdominal pain, nausea, and vomiting, assessed from daily diary entries completed by the parent or guardian |
| Treatment compliance | 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. |
| Adverse events | 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. |
Countries
Italy
Contacts
PRINCIPAL_INVESTIGATORDavide Sisti, PhD
University of Urbino "Carlo Bo"
Outcome results
None listed