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

NCT07235826 | Recruiting

• 1 other identifier: 140_16luglio_BactoblisEvol
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Recurrent Tonsillitis

Outcome Measures

Primary Outcomes (2)

• 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.

  6 months

• 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.

  6 months

Secondary Outcomes (6)

• Occurrence of adenotonsillar symptoms

  6 months

• Duration of adenotonsillar symptoms

  6 months

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

  6 months

• Number of school days missed

  6 months

• Number of antibiotic treatments prescribed for adenotonsillar infections

  6 months

Study Arms (2)

Bactoblis® Evol

EXPERIMENTAL

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®)

Placebo

PLACEBO COMPARATOR

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

Interventions

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.

Bactoblis® Evol

Placebo OTHER

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.

Also known as: Placebo (matching orodispersible tablet)

Placebo

Eligibility Criteria

• Age: 3 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Università di Urbino Carlo Bo

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

RECRUITING

Related Publications (6)

• 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.

  PMID: 40626761 BACKGROUND

• 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.

  PMID: 39597553 BACKGROUND

• 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.

  PMID: 27920580 BACKGROUND

• 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.

  PMID: 36873863 BACKGROUND

• 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.

  PMID: 23231486 BACKGROUND

• 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.

  PMID: 39338471 BACKGROUND

MeSH Terms

Conditions

Tonsillitis

Condition Hierarchy (Ancestors)

Pharyngitis; Respiratory Tract Infections; Infections; Pharyngeal Diseases; Stomatognathic Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

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: participants, caregivers, investigators, and outcome assessors are blinded to treatment allocation. The probiotic and placebo tablets are identical in appearance, packaging, and labeling.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Biochemistry and Experimental Medicine

Model Details: 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.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 19, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

IT (1)