Evaluation of the Efficacy of Streptococcus Salivarius Evol12® in the Reduction of Recurrent Adenotonsillitis in Children

November 17, 2025 updated by: Dr. Amjad Khan, Liaquat University of Medical & Health Sciences

Evaluation of the Efficacy of Streptococcus Salivarius Evol12® in the Reduction of Recurrent Adenotonsillitis in Children: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Cross-over Clinical Trial

This prospective, multicenter, randomized, double-blind, placebo-controlled, cross-over clinical trial will evaluate the efficacy and safety of Streptococcus salivarius Evol12® (Bactoblis® Evol) in reducing the recurrence and duration of acute febrile adenotonsillitis in children aged 3 to 11 years. Participants will receive either the probiotic or a matching placebo for 3 months, followed by a 7-day wash-out and a second 3-month treatment period with the alternative product. The study will assess changes in the incidence and duration of adenotonsillar episodes, antibiotic use, school absences, and sleep quality.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Recurrent adenotonsillitis in children is a frequent and burdensome condition, often leading to repeated antibiotic use, missed school days, and sleep disturbances. Streptococcus salivarius is a naturally occurring commensal bacterium of the oral microbiota with demonstrated ability to inhibit Streptococcus pyogenes and other pathogens responsible for pharyngotonsillitis. Streptococcus salivarius Evol12® is a novel probiotic strain with a safe microbiological profile and no antibiotic resistance, developed to restore oral microbial balance and reduce recurrent infections of the upper airways.

This non-profit, prospective, multicenter, randomized, double-blind, placebo-controlled, cross-over study will enroll 200 pediatric participants aged 3 to 11 years with a history of at least three documented episodes of acute febrile adenotonsillitis in the preceding 12 months. Participants will be randomized to receive either one orodispersible tablet of S. salivarius Evol12® (Bactoblis® Evol, PharmExtracta S.p.A., Italy) daily in the evening for 3 months followed by placebo for 3 months, or vice versa, with a 7-day wash-out period between treatments.

The primary objective is to evaluate the efficacy of S. salivarius Evol12® in reducing the duration and recurrence of acute febrile adenotonsillitis, as measured by the Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K).

Secondary objectives include assessment of sleep disorders (OSA-18 questionnaire), number and duration of feverish episodes, school days missed, antibiotic use, and symptom severity (e.g., sore throat, tonsil exudate, difficulty swallowing, otitis, cough, and fatigue).

Ethical approval has been granted by the Ethics Committee of the University of Urbino Carlo Bo (Minutes No. 96, July 24, 2025).

Study Type

Interventional

Enrollment (Estimated)

200

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
    • PU (Pesaro E Urbino)
      • Urbino, PU (Pesaro E Urbino), Italy, 61029

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

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male and female children aged 3 to 11 years.
  • History of ≥3 documented episodes of acute adenotonsillitis within the previous 12 months, each characterized by fever ≥38°C.
  • Signed and accepted informed consent from a parent or legal guardian.

Exclusion Criteria:

  • Total obstruction of the nasal cavities.
  • Uncontrolled gastroesophageal reflux disease.
  • Unilateral tonsillar enlargement.
  • Previous tonsil reduction surgery.
  • Lack of parental or legal guardian consent to participate in the study.

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: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bactoblis® Evol
Participants randomized to Sequence A will receive Streptococcus salivarius Evol12® (Bactoblis® Evol) for 3 months, followed by a 7-day wash-out, then matching placebo for 3 months. Bactoblis® Evol is taken as 1 orodispersible tablet nightly, allowed to dissolve slowly in the mouth.
Dietary supplement: Bactoblis® Evol (Streptococcus salivarius Evol12®)
Bactoblis® Evol is an orodispersible tablet containing the probiotic strain Streptococcus salivarius Evol12® (LMG P-33696), used to support the balance of the oral microbiota. Each tablet is taken once daily in the evening, allowing it to dissolve slowly in the mouth without chewing, eating, or drinking afterward. Treatment is administered for 3 consecutive months during each treatment period. The product is manufactured by PharmExtracta S.p.A., Pontenure, Italy.
Placebo Comparator: Placebo
Participants randomized to Sequence B will receive matching placebo for 3 months, followed by a 7-day wash-out, then Streptococcus salivarius Evol12® (Bactoblis® Evol) for 3 months. The placebo tablets are identical in appearance, taste, and packaging to the active product.
Other: Placebo
Matching placebo orodispersible tablet identical in appearance, flavor, and packaging to Bactoblis® Evol but without the active probiotic strain. Administered once daily in the evening for 3 months during the assigned treatment period.
Other Names:
  • Placebo (matching orodispersible tablet)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction in recurrence of acute febrile adenotonsillitis
Time Frame: 6 months
Number of febrile adenotonsillitis episodes occurring during the 6-month study period. Outcomes will be assessed using the Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K), completed during each febrile episode to record symptom severity and quality of life.
6 months
Reduction in duration of acute febrile adenotonsillitis episodes
Time Frame: 6 months
Duration (in days) of each febrile adenotonsillitis episode during the 6-month study period, assessed using the Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K) completed by caregivers during illness episodes.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of adenotonsillar symptoms
Time Frame: 6 months
Number of adenotonsillar symptom episodes (fever ≥38°C, sore throat, tonsil exudate, difficulty swallowing, earache, acute otitis media, fatigue or joint pain, swollen lymph nodes, or cough) reported by parents or guardians using an episode symptom card.
6 months
Duration of adenotonsillar symptoms
Time Frame: 6 months
Total duration (in days) of adenotonsillar symptom episodes (fever ≥38°C, sore throat, tonsil exudate, difficulty swallowing, earache, acute otitis media, fatigue or joint pain, swollen lymph nodes, or cough) reported by parents or guardians using an episode symptom card.
6 months
Change in sleep-related quality of life assessed by the Obstructive Sleep Apnea-18 (OSA-18) questionnaire
Time Frame: 6 months

Assessment of changes in sleep-related quality of life using the Obstructive Sleep Apnea-18 (OSA-18) questionnaire completed by the parent or legal guardian.

The OSA-18 total score ranges from 18 to 126, with higher scores indicating a worse sleep-related quality of life. The questionnaire evaluates symptoms and impact across five domains: sleep disturbance, physical suffering, emotional distress, daytime problems, and caregiver concerns.
6 months
Number of school days missed
Time Frame: 6 months
Total number of school days missed due to adenotonsillar infections during the study period, as recorded in the daily symptom card.
6 months
Number of antibiotic treatments prescribed for adenotonsillar infections
Time Frame: 6 months
otal number of antibiotic treatment courses prescribed for adenotonsillar infections during the 6-month study period, as reported by parents or legal guardians on the episode symptom card.
6 months
Duration of antibiotic treatment for adenotonsillar infections
Time Frame: 6 months
Total duration (in days) of antibiotic treatment courses prescribed for adenotonsillar infections during the 6-month study period, as reported by parents or legal guardians on the episode symptom card.
6 months

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"

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

September 1, 2025

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

November 14, 2025

First Submitted That Met QC Criteria

November 17, 2025

First Posted (Actual)

November 19, 2025

Study Record Updates

Last Update Posted (Actual)

November 19, 2025

Last Update Submitted That Met QC Criteria

November 17, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 140_16luglio_BactoblisEvol

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.

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