L. Reuteri ATCC PTA 5289 & L. Reuteri DSM 17938 for the Treatment of Children With Pharyngitis and/or Tonsillitis

Study Overview
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Brief Summary
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RCT in children (6m to 5y) with pharyngitis and/or tonsillitis who will be allocated to receive for 10 days L. reuteri DSM 17938 + L. reuteri ATCC PTA 5289) at a dose of 2x10^8 Colony Forming Units (CFU). Five drops are to be taken twice a day (in the morning and in the evening) or placebo drops, as treatment for clinical condition. Duration of symptoms and reduction of pain (odynophagia) severity during treatment will be measured as primary outcome

Detailed Description
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Rationale. Acute respiratory infections (ARIs) are a common problem in the first decade of life. The yearly prevalence of respiratory tract infections in an otherwise healthy 3-year old child is about three to 10 infections. Children between 6 months and 5 years are more prone to develop pharyngitis and tonsillitis compared to older children. 60-70% of children with F/T lies within this age group. Aetiology the pharyngitis and tonsillitis is viral in 70% of all cases In developing countries 6/10 cases are treated using antibiotics, regardless of clinical guidelines or standard of care documents recommending only to use symptomatic drugs (NSAID). Primary outcome. Duration of symptoms and reduction of pain (odynophagia) severity Secondary outcomes. Days with fever secondary to RTIs; Number of children receiving antibiotic treatment in each treatment group; Days of medical office visits or emergency visits; Total amount of medical office visits or emergency visits during the study, secondary to episodes of RTI; Days of absences from day care centre; Direct and Indirect costs Total costs of treatments including visit to private office, visit to emergency department, cost of treatment (NSAIDs + Probiotics vs NSAIDs + Placebo); Frequency of adverse events; Viral/bacterial load (multiplex-PCR); IgA in saliva and Change in salivary inflammatory biomarkers. Interventions. L. reuteri DSM 17938 + L. reuteri ATCC PTA 5289) will be given at a dose of 2x10^8 Colony Forming Units (CFU). Five drops are to be taken twice a day (in the morning and in the evening) giving a daily dose of 4x108 CFU/day. The placebo drops will have identical ingredients except for lacking the bacteria. Five drops are to be taken twice a day (in the morning and in the evening).

Official Title
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Randomized Controlled Trial on the Safety and Efficacy of L. Reuteri ATCC PTA 5289 & L. Reuteri DSM 17938 for the Treatment of Children With Pharyngitis and/or Tonsillitis: A Proof of Concept

Conditions
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Pharyngitis, Tonsillitis

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Infants suffering from pharyngitis and/or tonsillitis Born at term (36 weeks of gestation) Any gender 6 months to 5 years old Birth weight >2500 g Same socioeconomic background Written informed consent from at least one parent or legal guardian Exclusion Criteria: Use of antibiotics or probiotic products 2 weeks' prior inclusion in the study Eight or more new ear infections (otitis media) within 12 months Two or more serious sinus infections within 12 months Two or more episodes of pneumonia within 12 months Two or more invasive infections in the history (meningitis, cellulitis, osteomyelitis, septicaemia) Failure to gain weight or grow normally Chronic diarrhoea Recurrent deep skin or organ abscesses, Persistent superficial candidiasis after 1 year of age Use of two or more months on antibiotics for respiratory infections on the last year before considered eligible Gastroesophageal reflux Allergy Asthma A1-antitrypsin deficeincy Primary or secondary ciliary dyskenisia Congenital anomalies of respiratory tract Supplementation of probiotics 2 weeks before inclusion in the study and during the whole study period If the mother is breastfeeding the child participating in the trial the mother should not use supplementation of probiotics 2 weeks before and during the study period Concurrent participation in other clinical trials

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial, double blind allocation concealment, parallel assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>L. reuteri ATCC PTA 5289 + L. reuteri DSM 17938 at a dose of 2x10^8 Colony Forming Units (CFU) | Dietary Supplement: Probiotic<br>* L. reuteri Prodentis oil drops (L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289) will be given at a dose of 2x108 Colony Forming Units (CFU). Five drops are to be taken twice a day (in the morning and in the evening) giving a daily dose of 4x108 CFU/day.<br>|
| Placebo Comparator: Placebo<br>Five drops of Placebo taken twice a day (in the morning and in the evening). | Other: Placebo<br>* Five drops of Placebo taken twice a day (in the morning and in the evening).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Improvement | Duration of respiratory symptoms | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fever improvement | Total number of hours during the study that the child is with temperature >37.5oC measured twice a day since the moment they start to use the interventions and until the last visit into the study | 10 days | 
| Use of antibiotics | Total amount of days of antibiotic use during the study, secondary to the presence of episodes of RTI, reported since the beginning of the study products administration until the last visit occur | 10 days | 
| Medical/Emergency visits | Total amount of medical office visits or emergency visits during the study, secondary to episodes of RTI, reported since the beginning of the study products administration until the last visit occurs | 10 days | 
| Abseentisim | Total amount of days of absences from the day care centre during the study, secondary to the presence of episodes of RTI, reported since the beginning of the study products administration until the last visit occurs. | 10 days | 
| Costs of intervention | Total costs of treatments including visit to private office, visit to emergency department, cost of treatment (NSAIDs + Probiotics vs NSAIDs + Placebo) | 10 days | 
| Adverse events | Total number of adverse events which be reported by parents starting after randomization and finishing at the moment of last visit | 10 days | 
| Inflammatory improvements | Changes in IgA in saliva | 10 days |