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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
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Probiotic | Experimental | L. reuteri ATCC PTA 5289 + L. reuteri DSM 17938 at a dose of 2x10^8 Colony Forming Units (CFU) |
|
| Placebo | Placebo Comparator | Five drops of Placebo taken twice a day (in the morning and in the evening). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Probiotic | Dietary Supplement | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Improvement | Duration of respiratory symptoms | 10 days |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pedro Gutierrez Castrellon, MD, MSc, DSc | Innovacion y Desarrollo de Estrategias en Salud | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital General Dr. Manuel Gea Gonzalez | Mexico City | Tlalpan | 14080 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28674113 | Result | Laursen RP, Larnkjaer A, Ritz C, Hauger H, Michaelsen KF, Molgaard C. Probiotics and Child Care Absence Due to Infections: A Randomized Controlled Trial. Pediatrics. 2017 Aug;140(2):e20170735. doi: 10.1542/peds.2017-0735. Epub 2017 Jul 3. | |
| 26463725 | Result | Gerasimov SV, Ivantsiv VA, Bobryk LM, Tsitsura OO, Dedyshin LP, Guta NV, Yandyo BV. Role of short-term use of L. acidophilus DDS-1 and B. lactis UABLA-12 in acute respiratory infections in children: a randomized controlled trial. Eur J Clin Nutr. 2016 Apr;70(4):463-9. doi: 10.1038/ejcn.2015.171. Epub 2015 Oct 14. |
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| ID | Term |
|---|---|
| D010612 | Pharyngitis |
| D014069 | Tonsillitis |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D010608 | Pharyngeal Diseases |
| D009057 | Stomatognathic Diseases |
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| ID | Term |
|---|---|
| D019936 | Probiotics |
| ID | Term |
|---|---|
| D019587 | Dietary Supplements |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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Randomized controlled trial, double blind allocation concealment, parallel assignment
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Randomization list will by assembled by independient organization not related with participant, care provider, investigators or sponsors. eCRF will include randomization selection
|
| Placebo | Other | Five drops of Placebo taken twice a day (in the morning and in the evening). |
|
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 |
| 26372517 | Result | Taipale TJ, Pienihakkinen K, Isolauri E, Jokela JT, Soderling EM. Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in early childhood. Pediatr Res. 2016 Jan;79(1-1):65-9. doi: 10.1038/pr.2015.174. Epub 2015 Sep 15. |
| 21873895 | Result | Maldonado J, Canabate F, Sempere L, Vela F, Sanchez AR, Narbona E, Lopez-Huertas E, Geerlings A, Valero AD, Olivares M, Lara-Villoslada F. Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants. J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):55-61. doi: 10.1097/MPG.0b013e3182333f18. |
| 20485304 | Result | Merenstein D, Murphy M, Fokar A, Hernandez RK, Park H, Nsouli H, Sanders ME, Davis BA, Niborski V, Tondu F, Shara NM. Use of a fermented dairy probiotic drink containing Lactobacillus casei (DN-114 001) to decrease the rate of illness in kids: the DRINK study. A patient-oriented, double-blind, cluster-randomized, placebo-controlled, clinical trial. Eur J Clin Nutr. 2010 Jul;64(7):669-77. doi: 10.1038/ejcn.2010.65. Epub 2010 May 19. |
| D012140 |
| Respiratory Tract Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D019602 |
| Food and Beverages |