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Recurrent TonsillitisNCT07235826

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

A study testing Bactoblis® Evol (Streptococcus salivarius Evol12®) in people with Recurrent Tonsillitis, run by Liaquat University of Medical & Health Sciences at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 3 to 11 years
Conditions the study is for
Recurrent Tonsillitis
What is being tested?
Bactoblis® Evol (Streptococcus salivarius Evol12®)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
216 participants
Where
1 siteItaly
Study dates
26 Nov 2025to 23 Jul 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 11 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • Università di Urbino Carlo Bo

    Urbino, PU (Pesaro E Urbino), 61029

Other trials in Italy

About this study

Official title: 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.

Read the 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 216 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).

Being tested
Bactoblis® Evol (Streptococcus salivarius Evol12®), Placebo
Medical subject headings
Tonsillitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bactoblis® Evol (Streptococcus salivarius Evol12®)Dietary supplement

    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.

  • PlaceboOther

    Also called Placebo (matching orodispersible tablet)

    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.

Study groups in NCT07235826
Study groupRoleWhat they receive
Bactoblis® EvolExperimentalParticipants 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.
Receives: Dietary Supplement: Bactoblis® Evol (Streptococcus salivarius Evol12®)
PlaceboPlacebo comparatorParticipants 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.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction in recurrence of acute febrile adenotonsillitis

    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.

    Measured: 6 months

  2. Reduction in duration of acute febrile adenotonsillitis episodes

    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.

    Measured: 6 months

Secondary outcomes (6)
  1. Occurrence of adenotonsillar symptoms

    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.

    Measured: 6 months

  2. Duration of adenotonsillar symptoms

    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.

    Measured: 6 months

  3. Change in sleep-related quality of life assessed by the Obstructive Sleep Apnea-18 (OSA-18) questionnaire

    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.

    Measured: 6 months

  4. Number of school days missed

    Total number of school days missed due to adenotonsillar infections during the study period, as recorded in the daily symptom card.

    Measured: 6 months

  5. Number of antibiotic treatments prescribed for adenotonsillar infections

    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.

    Measured: 6 months

  6. Duration of antibiotic treatment for adenotonsillar infections

    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.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2025
  2. Study start26 Nov 2025
  3. Primary completion23 Jul 2026
  4. Study completion23 Jul 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Crossover
Model description
Participants will be randomized in a 1:1 ratio to receive either Streptococcus salivarius Evol12® (Bactoblis® Evol) for 3 months followed by placebo for 3 months, or the reverse sequence, with a 7-day wash-out period between treatment phases.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
216 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07235826
Sponsor's protocol ID
140_16luglio_BactoblisEvol
Status last verified
Jul 2026
First submitted
14 Nov 2025
Last updated
24 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Di Pierro F, Thacharodi A, Kumaraswami M, Bertuccioli A, Tanda ML, Zerbinati N. Description of the draft genome sequence of Streptococcus salivarius eK12, a derivative of the probiotic strain Streptococcus salivarius K12 with a modified plasmid. Microbiol Resour Announc. 2025 Aug 14;14(8):e0035525. doi: 10.1128/mra.00355-25. Epub 2025 Jul 8.

    PubMed 40626761
  • Bertuccioli A, Cardinali M, Micucci M, Rocchi MBL, Palazzi CM, Zonzini GB, Annibalini G, Belli A, Sisti D. Efficacy of Streptococcus salivarius Blis K12 in the Prevention of Upper Respiratory Tract Infections in Physically Active Individuals: A Randomized Controlled Trial. Microorganisms. 2024 Oct 26;12(11):2164. doi: 10.3390/microorganisms12112164.

    PubMed 39597553
  • Di Pierro F, Colombo M, Zanvit A, Rottoli AS. Positive clinical outcomes derived from using Streptococcus salivarius K12 to prevent streptococcal pharyngotonsillitis in children: a pilot investigation. Drug Healthc Patient Saf. 2016 Nov 21;8:77-81. doi: 10.2147/DHPS.S117214. eCollection 2016.

    PubMed 27920580
  • La Torre F, Sota J, Insalaco A, Conti G, Del Giudice E, Lubrano R, Breda L, Maggio MC, Civino A, Mastrorilli V, Loconte R, Natale MF, Celani C, Romeo M, Patroniti S, Gentile C, Vitale A, Caggiano V, Gaggiano C, Diomeda F, Cattalini M, Lopalco G, Emmi G, Parronchi P, Gentileschi S, Cardinale F, Aragona E, Shahram F, Marino A, Barone P, Moscheo C, Ozkiziltas B, Carubbi F, Alahmed O, Iezzi L, Ogunjimi B, Mauro A, Tarsia M, Mahmoud AAA, Giardini HAM, Sfikakis PP, Laskari K, Wiesik-Szewczyk E, Hernandez-Rodriguez J, Frediani B, Gomez-Caverzaschi V, Tufan A, Almaghlouth IA, Balistreri A, Ragab G, Fabiani C, Cantarini L, Rigante D. Preliminary data revealing efficacy of Streptococcus salivarius K12 (SSK12) in Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome: A multicenter study from the AIDA Network PFAPA syndrome registry. Front Med (Lausanne). 2023 Feb 16;10:1105605. doi: 10.3389/fmed.2023.1105605. eCollection 2023.

    PubMed 36873863
  • Wescombe PA, Hale JD, Heng NC, Tagg JR. Developing oral probiotics from Streptococcus salivarius. Future Microbiol. 2012 Dec;7(12):1355-71. doi: 10.2217/fmb.12.113.

    PubMed 23231486
  • Rajasekaran JJ, Krishnamurthy HK, Bosco J, Jayaraman V, Krishna K, Wang T, Bei K. Oral Microbiome: A Review of Its Impact on Oral and Systemic Health. Microorganisms. 2024 Aug 29;12(9):1797. doi: 10.3390/microorganisms12091797.

    PubMed 39338471

Questions about this trial

What is this clinical trial studying?

A study testing Bactoblis® Evol (Streptococcus salivarius Evol12®) in people with Recurrent Tonsillitis, run by Liaquat University of Medical & Health Sciences at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction in recurrence of acute febrile adenotonsillitis (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07235826, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.

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