Streptococcus Pyogenes PharyngotonsillitisNCT06370208
Prophylactic Effect of Probiotic Streptococcus Salivarius eK12 Against Recurrent Streptococcus Pyogenes Pharyngotonsillitis Infection in Pediatrics
A study testing Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12) and Oral vit D3 in people with Streptococcus Pyogenes Pharyngotonsillitis, run by Liaquat University of Medical & Health Sciences at 4 sites in Pakistan.
Trial summary
Recurrent Group A Streptococcus (GAS) infections, primarily presenting as strep throat, are a significant health concern in pediatric populations, leading to symptoms like sore throat, fever, and swollen lymph nodes. Read more about this study
- Who is it for?
- Ages 3 to 11 yearsHealthy volunteers can take part
- Conditions the study is for
- Streptococcus Pyogenes Pharyngotonsillitis
- What is being tested?
- Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12) and Oral vit D3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 4 sitesPakistan
- Study dates
- 1 Dec 2025to 31 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
- Healthy volunteers accepted
- Child
Who may be able to join
- Children aged 3-11 years.
- Recent history of documented recurrent episodes of Streptococcus pyogenes pharyngo- tonsillitis infection in the last 6 months, or 4 or more episodes in the last 12 months (S.
- pyogenes infection being defined as: McIsaac score with clinical score ≥ 2 plus confirmation of S. pyogenes presence with rapid throat swab (RAD) method or McIsaac score =5.
- Willingness to comply with the study protocol and attend scheduled follow-up visits.
- Written informed consent obtained from the parent or legal guardian.
Who cannot join
- Children with known allergies or hypersensitivity to probiotics or any components of the study product.
- Current use of antibiotics or within the past 30 days.
- Used oral colonizing probiotics in the last 6 months.
- Presence of severe underlying medical conditions affecting the immune system or gastrointestinal tract.
- Participation in other clinical trials involving investigational drugs or interventions.
- Inability to adhere to the study requirements due to logistical or social reasons.
Show all 11Show fewer
- History of rheumatic disorders, bronchospasm, severe asthma, or allergy requiring corticosteroids.
- Past tonsillectomy or an indication for adeno-tonsillectomy; or severe respiratory or systemic disorders
- Individuals immunocompromised or had a condition favouring recurrent Acute Otitis Media (AOM), including severe atopy, acquired or congenital immunodeficiency, cleft palate, craniofacial abnormalities, obstructive adenoids, a chronically ruptured eardrum, sleep apnoea, or tympanostomy tubes
- Children undergoing current pharmacological therapies to prevent recurrent respiratory infections.
- Any other medical condition or circumstance that, in the investigator's judgment, would compromise the safety of the participant or the integrity of the study.
Trial locations and contacts
4 sites in 1 country.
Pakistan4 sites
Dr. Khan Afsar ENT Clinic
Haripur, Khyber Pakhtunkhwa, 22620
CDF Hospital (Bilawal Medical College, LUMHS)
Hyderābād, Sindh, 71000
Dr. Allah Wadhayo Kallo Clinic (Shifa Hurmat Diagnostic and Research Centre)
Hyderābād, Sindh, 71500
Saboor Clinic
Quetta, Balouchistan, 87300
About this study
Official title: Study to Investigate the Prophylactic Effect of Streptococcus Salivarius eK12 Against Recurrent Group A Streptococcal Pharyngotonsillitis in Children: A Randomized, Double-Blind, Parallel-Group Controlled Trial
Recurrent Group A Streptococcus (GAS) infections, primarily presenting as strep throat, are a significant health concern in pediatric populations, leading to symptoms like sore throat, fever, and swollen lymph nodes. GAS is highly contagious and can spread easily among children in close-contact environments like schools and daycare centers, often resulting in frequent re-infections. Managing these recurrent infections typically requires antibiotics, but reliance on antibiotics carries risks, including resistance development, gut microbiota disruption, and various side effects. Probiotic therapy, particularly with Streptococcus salivarius K12, has shown promise as a preventive approach, utilizing competitive exclusion and antimicrobial production to inhibit GAS growth in the oral cavity. Recent studies have advanced this with the development of S. salivarius eK12, a re-engineered strain that enhances efficacy against GAS by preventing the survival-promoting interactions between the probiotic and pathogenic bacteria. This modified strain, now registered as Bactoblis® EVOL in Italy (EU), holds potential as an effective version to reduce the incidence and severity of GAS infections without the drawbacks of antibiotic therapy.
Read the detailed description
The primary aim of this clinical trial is to evaluate whether prophylactic use of S. salivarius eK12 can effectively reduce the frequency of strep throat episodes in children. By assessing the efficacy of S. salivarius eK12 supplementation, this study seeks to provide insights into its potential as a non-antibiotic preventive strategy for recurrent strep throat infections in pediatric populations.
- Being tested
- Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12), Oral vit D3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12)Dietary supplement
Bactoblis® EVOL: containing one billion CFU of probiotic Streptococcus salivarius eK12
Oral vit D3Dietary supplement
Oral vit D3 tablets (200 IU)
| Study group | Role | What they receive |
|---|---|---|
| Probiotic supplement group | Experimental | Participants in this group will receive probiotic Streptococcus salivarius eK12 (Bactoblis® EVOL containing ca. 1 billion CFU of Streptococcus salivarius eK12/capsule) as daily one orally dissolving tablet (to be slowly dissolved in the mouth before sleeping at night time), plus 200 IU vit D3 (one tablet) for 3-months. Receives: Dietary Supplement: Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12); Dietary Supplement: Oral vit D3 |
| Control group | Active comparator | Participants in this group will receive only 200 IU vit D3 as daily two orally dissolving tablets under the same dosing regimen. Receives: Dietary Supplement: Oral vit D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence of Streptococcus pyogenes pharyngotonsillitis infection
Number of episodes of Streptococcus pyogenes pharyngotonsillitis infection
Measured: 6-months
Secondary outcomes (10)
Severity of Group A Streptococcal (GAS) Symptoms
Severity of GAS-associated symptoms assessed using a 10-point Visual Analogue Scale (VAS)
Measured: 6-months
Protection against viral infection
Number of incidences of viral throat infection
Measured: 6-months
Protection against Acute Otitis Media infection
Number of incidences of Acute Otitis Media infection
Measured: 6-months
Protection against respiratory infection
Number of incidences of Tracheitis infection
Measured: 6-months
Protection against Rhinitis
Number of incidences of Rhinitis
Measured: 6-months
Protection against flu
Number of incidences of flu
Measured: 6-months
Protection against Enteritis
Number of incidences of Enteritis infection
Measured: 6-months
Protection against Stomatitis
Number of incidences of Stomatitis infection
Measured: 6-months
Use of Antibiotics
Number of antibiotic courses prescribed during the 6-month study period.
Measured: 6-months
Persistence of Streptococcus salivarius eK12 in saliva after washout
Post hoc exploratory ancillary analysis, conceived after study completion and unblinding, evaluating the presence of the administered Streptococcus salivarius eK12 strain in saliva at the end of the 6-month study period, approximately 3 months after discontinuation of eK12 supplementation. Saliva samples will be examined using a strain-specific microbiological or molecular method capable of distinguishing eK12 from the parental K12 strain. The outcome will be reported as the proportion of participants with detectable eK12 and, if a validated quantitative method is used, the salivary abundance of eK12. This analysis was not a prespecified outcome of the original clinical trial.
Measured: Month 6, approximately 3 months after discontinuation of eK12 supplementation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2024
- Study start1 Dec 2025
- Primary completion31 Jul 2026
- Study completion31 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Streptococcus Pyogenes PharyngotonsillitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liaquat University of Medical & Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Università degli Studi dell'Insubria
- Responsible party
- Principal investigator, Dr. Amjad Khan, Liaquat University of Medical & Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06370208
- Sponsor's protocol ID
- LUMHS/REC/-496/11.11.2024
- Status last verified
- Aug 2026
- First submitted
- 13 Apr 2024
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data underlying the results reported in the published article, together with the corresponding data dictionary.
Publications
Di Pierro F, Veeraraghavan G, Kalaiselvan K, Ashif B, Jeyakumar L, Gopalakrishnan G, Cazzaniga M, Bertuccioli A, Tanda ML, Zerbinati N, Ujjan I, Bugti AA, Bano A, Gull Y, Mumtaz N, Khan A. In Vitro and In Vivo Safety Evaluation of Streptococcus salivarius eK12, a Genetically Modified Dietary Probiotic Derived from the Oral Probiotic S. salivarius K12. J Microbiol Biotechnol. 2025 Dec 9;35:e2509016. doi: 10.4014/jmb.2509.09016.
PubMed 41391486Di Pierro F, Bugti AA, Bano A, Kara M, Ujjan I, Mumtaz N, Gull Y, Cazzaniga M, Bertuccioli A, Tanda ML, Zerbinati N, Hameed S, Khan A. Study to evaluate the safety and tolerability of Streptococcus salivarius eK12, a genetically modified strain derived from the oral probiotic S. salivarius K12: Results from a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Front Nutr. 2025 Dec 8;12:1701611. doi: 10.3389/fnut.2025.1701611. eCollection 2025.
PubMed 41438195Di Pierro F, Colombo M, Giuliani MG, Danza ML, Basile I, Bollani T, Conti AM, Zanvit A, Rottoli AS. Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children. Eur Rev Med Pharmacol Sci. 2016 Nov;20(21):4601-4606.
PubMed 27874935Di 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 27920580Di Pierro F, Colombo M, Zanvit A, Risso P, Rottoli AS. Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children. Drug Healthc Patient Saf. 2014 Feb 13;6:15-20. doi: 10.2147/DHPS.S59665. eCollection 2014.
PubMed 24600248Di Pierro F, Donato G, Fomia F, Adami T, Careddu D, Cassandro C, Albera R. Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media. Int J Gen Med. 2012;5:991-7. doi: 10.2147/IJGM.S38859. Epub 2012 Nov 30.
PubMed 23233809
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Investigate the Prophylactic Effect of Streptococcus Salivarius eK12 Against Recurrent Group A Streptococcal Pharyngotonsillitis in Children: A Randomized, Double-Blind, Parallel-Group Controlled Trial
- ClinicalTrials.gov ID
- NCT06370208
- Acronym / sponsor ID
- LUMHS/REC/-496/11.11.2024
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Liaquat University of Medical & Health SciencesUniversity, hospital or other
- Collaborators
- Università degli Studi dell'Insubria
- Study start
- 1 Dec 2025 (actual)
- Primary completion
- 31 Jul 2026 (actual)
- Study completion
- 31 Jul 2026 (actual)
- First posted
- 17 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recurrent Group A Streptococcus (GAS) infections, primarily presenting as strep throat, are a significant health concern in pediatric populations, leading to symptoms like sore throat, fever, and swollen lymph nodes. GAS is highly contagious and can spread easily among children in close-contact environments like schools and daycare centers, often resulting in frequent re-infections. Managing these recurrent infections typically requires antibiotics, but reliance on antibiotics carries risks, including resistance development, gut microbiota disruption, and various side effects. Probiotic therapy, particularly with Streptococcus salivarius K12, has shown promise as a preventive approach, utilizing competitive exclusion and antimicrobial production to inhibit GAS growth in the oral cavity. Recent studies have advanced this with the development of S. salivarius eK12, a re-engineered strain that enhances efficacy against GAS by preventing the survival-promoting interactions between the probiotic and pathogenic bacteria. This modified strain, now registered as Bactoblis® EVOL in Italy (EU), holds potential as an effective version to reduce the incidence and severity of GAS infections without the drawbacks of antibiotic therapy.
Detailed description
The primary aim of this clinical trial is to evaluate whether prophylactic use of S. salivarius eK12 can effectively reduce the frequency of strep throat episodes in children. By assessing the efficacy of S. salivarius eK12 supplementation, this study seeks to provide insights into its potential as a non-antibiotic preventive strategy for recurrent strep throat infections in pediatric populations.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic supplement group | Experimental | Dietary Supplement: Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12), Dietary Supplement: Oral vit D3Participants in this group will receive probiotic Streptococcus salivarius eK12 (Bactoblis® EVOL containing ca. 1 billion CFU of Streptococcus salivarius eK12/capsule) as daily one orally dissolving tablet (to be slowly dissolved in the mouth before sleeping at night time), plus 200 IU vit D3 (one tablet) for 3-months. |
| Control group | Active comparator | Dietary Supplement: Oral vit D3Participants in this group will receive only 200 IU vit D3 as daily two orally dissolving tablets under the same dosing regimen. |
Who may qualify
- Ages
- 3 to 11 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Children aged 3-11 years.
- Recent history of documented recurrent episodes of Streptococcus pyogenes pharyngo- tonsillitis infection in the last 6 months, or 4 or more episodes in the last 12 months (S.
- pyogenes infection being defined as: McIsaac score with clinical score ≥ 2 plus confirmation of S. pyogenes presence with rapid throat swab (RAD) method or McIsaac score =5.
- Willingness to comply with the study protocol and attend scheduled follow-up visits.
- Written informed consent obtained from the parent or legal guardian.
Key exclusion criteria (11 listed)
- Children with known allergies or hypersensitivity to probiotics or any components of the study product.
- Current use of antibiotics or within the past 30 days.
- Used oral colonizing probiotics in the last 6 months.
- Presence of severe underlying medical conditions affecting the immune system or gastrointestinal tract.
- Participation in other clinical trials involving investigational drugs or interventions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12)Bactoblis® EVOL: containing one billion CFU of probiotic Streptococcus salivarius eK12 | Dietary supplement | Probiotic supplement group |
| Oral vit D3Oral vit D3 tablets (200 IU) | Dietary supplement | Control group, Probiotic supplement group |
Primary outcome
Recurrence of Streptococcus pyogenes pharyngotonsillitis infection
Time frame: 6-months
Number of episodes of Streptococcus pyogenes pharyngotonsillitis infection
10 secondary outcomes
Severity of Group A Streptococcal (GAS) Symptoms
Time frame: 6-months
Protection against viral infection
Time frame: 6-months
Protection against Acute Otitis Media infection
Time frame: 6-months
Protection against respiratory infection
Time frame: 6-months
Protection against Rhinitis
Time frame: 6-months
Protection against flu
Time frame: 6-months
Protection against Enteritis
Time frame: 6-months
Protection against Stomatitis
Time frame: 6-months
Use of Antibiotics
Time frame: 6-months
Persistence of Streptococcus salivarius eK12 in saliva after washout
Time frame: Month 6, approximately 3 months after discontinuation of eK12 supplementation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Background: PubMed 41391486Di Pierro F, Veeraraghavan G, Kalaiselvan K, Ashif B, Jeyakumar L, Gopalakrishnan G, Cazzaniga M, Bertuccioli A, Tanda ML, Zerbinati N, Ujjan I, Bugti AA, Bano A, Gull Y, Mumtaz N, Khan A. In Vitro and In Vivo Safety Evaluation of Streptococcus salivarius eK12, a Genetically Modified Dietary Probiotic Derived from the Oral Probiotic S. salivarius K12. J Microbiol Biotechnol. 2025 Dec 9;35:e2509016. doi: 10.4014/jmb.2509.09016.
- Background: PubMed 41438195Di Pierro F, Bugti AA, Bano A, Kara M, Ujjan I, Mumtaz N, Gull Y, Cazzaniga M, Bertuccioli A, Tanda ML, Zerbinati N, Hameed S, Khan A. Study to evaluate the safety and tolerability of Streptococcus salivarius eK12, a genetically modified strain derived from the oral probiotic S. salivarius K12: Results from a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Front Nutr. 2025 Dec 8;12:1701611. doi: 10.3389/fnut.2025.1701611. eCollection 2025.
- Results publication: PubMed 27874935Di Pierro F, Colombo M, Giuliani MG, Danza ML, Basile I, Bollani T, Conti AM, Zanvit A, Rottoli AS. Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children. Eur Rev Med Pharmacol Sci. 2016 Nov;20(21):4601-4606.
- Results publication: PubMed 27920580Di 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.
- Results publication: PubMed 24600248Di Pierro F, Colombo M, Zanvit A, Risso P, Rottoli AS. Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children. Drug Healthc Patient Saf. 2014 Feb 13;6:15-20. doi: 10.2147/DHPS.S59665. eCollection 2014.
- Results publication: PubMed 23233809Di Pierro F, Donato G, Fomia F, Adami T, Careddu D, Cassandro C, Albera R. Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media. Int J Gen Med. 2012;5:991-7. doi: 10.2147/IJGM.S38859. Epub 2012 Nov 30.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data underlying the results reported in the published article, together with the corresponding data dictionary.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12) and Oral vit D3 in people with Streptococcus Pyogenes Pharyngotonsillitis, run by Liaquat University of Medical & Health Sciences at 4 sites in Pakistan.
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 5 inclusion and 11 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 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Pakistan. 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. 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?
Recurrence of Streptococcus pyogenes pharyngotonsillitis infection (time frame: 6-months). 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 NCT06370208, 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 21 Aug 2026.