Pharyngitis, Tonsillitis, Upper Respiratory Tract Infections
Conditions
Keywords
Probiotic
Brief summary
Randomized, placebo-controlled trial to evaluate the coadjuvant effect of a combination of L. plantarum and P. acidilactici probiotic strains, taken twice daily, in children 6 months to 5 years-old with upper respiratory tract infections with pharyngitis and/or tonsillitis. Main objective is to evaluate efficacy of this probiotic in reducing fever and pain, as well to evaluate its safety.
Detailed description
Randomized, placebo-controlled trial (RCT) to evaluate the coadjuvant effect of probiotic strains L. plantarum CECT30292, L.plantarum CECT7484 and CECT7485 together with P. acidilactici CECT7483, taken twice daily, in children 6 months to 5 years-old with upper respiratory tract infections with pharyngitis and/or tonsillitis, as diagnosed by a physician. Main objective is to evaluate efficacy of this probiotic in reducing fever (as per infrared thermometer, same model for all recruited subjects) and pain (as per FLACC scale \[Face, Legs, Activity, Cry and Consolability\]), as well to evaluate its safety. Secondary objectives include effect on cough, rhinorrhea, nasal congestion, use of concomitant medication, emergency visits, hospitalizations, schooling absences and salivary immune markers. Probiotic intervention will last 15 days, and patients will return for follow-up visits on the last day of probiotic intervention (day 15), and well as day 30 and 60. The study aims at enrolling and randomizing 80 children fulfilling entry criteria and living in Mexico City area (2,200m over the sea level), after parents or legal guardians sign informed consent.
Interventions
DIETARY_SUPPLEMENTProbiotic
Combination of strains Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and Pediococcus acidilactici CECT7483, twice daily for 15 days
OTHERPlacebo
Combination of maltodextrin (E1400, qs) in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0, twice daily for 15 days
Sponsors
Innovacion y Desarrollo de Estrategias en Salud
Hospital General Dr. Manuel Gea González
AB Biotics, SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All study staff, including the Principal Investigator and the persons performing the subject assessments, will be blinded during the study. Sealed individual treatment code envelopes will be kept at the clinic to be able to break the code if any emergency occurs, as judged by the Investigator
Intervention model description
Randomized controlled trials. Study subjects (6 months to 5 years-old) will be allocated to receive a combination of strains Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and P. acidilactici CECT7483 (arm one) or placebo (arm two)
Eligibility
Sex/Gender
ALL
Age
6 Months to 5 Years
Healthy volunteers
No
Inclusion criteria
* Male and female children, 6 months to 5 years-old * Diagnosed with upper respiratory tract infection with pharyngitis and/or tonsillitis by a physician * With fever \>37.5 Celsius degrees and FLACC (Face, Legs, Activity, Cry and Consolability) score \>3 * Symptom onset no more than 48h before study entry * Body weight at birth \>2500 gr * Informed consent provided by parents or legal guardians
Exclusion criteria
* Failure to thrive * Asthma or significant allergic disease * Use of antibiotics, antivirals, probiotics or prebiotics for more than 48h within 2 weeks of study entry * History of recurrent respiratory infections (\>2 otitis, \>1 severe sinusitis or \>1 pneumonia) within 12 months of study entry * History of 2 or more invasive infections (meningitis, cellulitis, osteomyelitis, sepsis) * Chronic diarrhea or short bowel syndrome * Congenital heart or respiratory deficiency * Known alpha1-antitrypsin deficiency * Concurrent participation in other clinical trial(s) * Other particular conditions which, in the judgment of the Principal Investigator, may interfere with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily evolution of pain | Day 1 to 15 | Daily severity of pain, as per FLACC scale (Face, Legs, Activity, Cry and Consolability, ranging 0 \[no pain\] to 10 \[maximum pain\]) and noted in patient diary |
| Daily evolution of fever | Day 1 to 15 | Daily severity of fever (Celsius degrees), as measured with an infrared thermometer (same model for all recruited subjects) and noted in patient diary |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fever Area Under the Curve | Day 1 to 60 | Area Under the Curve (AUC) of daily fever (body temperature, Celsius degrees) |
| Pain Area Under the Curve | Day 1 to 60 | Area Under the Curve (AUC) of daily pain, as per FLACC scale (Face, Legs, Activity, Cry and Consolability, ranging 0 \[no pain\] to 10 \[maximum pain\]) |
| Days with pain | Day 1 to 60 | Days with pain as per FLACC scale (Face, Legs, Activity, Cry and Consolability), as noted in patient diary |
| Days with rhinorrhea | Day 1 to 60 | Days with runny nose, as noted in patient diary |
| Days with cough | Day 1 to 60 | Days of cough, as noted in patient diary |
| Days with nasal congestion | Day 1 to 60 | Days of nasal congestion, as noted in patient diary |
| Days with any symptom | Day 1 to 60 | Days with one or more of the following symptom: fever, pain, rhinorrhea, cough or nasal congestion (as noted in patient diary) |
| Days with concomitant medication | Day 1 to 60 | Days of intake of NSAIDS (non-steroidal anti-inflammatory drugs) and/or antihistamines, as noted in patient diary |
| Number of children receiving antibiotics | Day 1 to 60 | Number of children receiving antibiotics |
| Number of hospitalizations | Day 1 to 60 | Number of children being hospitalized related to respiratory tract infection |
| Days of schooling absence | Day 1 to 60 | Days of daycare or kindergarten absence, as noted in patient diary |
| Change in salivary immune biomarkers | Day 1 to 15 | Change in concentration of Immunoglobulin A (IgA), Tumor Necrosis Factor-alpha (TNFa), Interleukin 1-beta (IL-1b) and Interleukin 10 (IL-10) in saliva samples |
| Total treatment costs | Day 1 to 60 | Cost of medical and emergency visits, drug treatments (anti-inflammatory drugs, anti-histamines and antibiotics) and schooling absence |
| Time to fever resolution | Day 1 to 15 | Time to body temperature at or below 37.5 Celsius, as noted in patient diary |
| Time to pain resolution | Day 1 to 15 | Time to FLACC (Face, Legs, Activity, Cry and Consolability, ranging 0 \[no pain\] to 10 \[maximum pain\]) score \< 2, as noted in patient diary |
| Time to complete symptom resolution | Day 1 to 15 | Time to clearance of all of the following symptoms: fever, pain, rhinorrhea, cough and nasal congestion, as noted in patient diary |
| Time to fever recurrence | Day 15 to 60 | Time to body temperature \>37.5 Celsius after initial resolution (see outcome #19), as noted in patient diary |
| Time to pain recurrence | Day 15 to 60 | Time to FLACC (Face, Legs, Activity, Cry and Consolability, ranging 0 \[no pain\] to 10 \[maximum pain\]) score \> 3 after initial resolution (see outcome #20), as noted in patient diary |
| Time to any symptom recurrence | Day 15 to 60 | Time to recurrence of any symptom (fever, pain, rhinorrhea, cough and nasal congestion) after initial complete symptom resolution (see outcome #21), as noted in patient diary |
| Change in microbiota | Day 1 to 15 | Change in microbiota composition, as determined by 16S gene sequencing |
| Number of medical or emergency visits | Day 1 to 60 | Number of medical or emergency visits related to respiratory tract infection |
| Days with fever | Day 1 to 60 | Days with body temperature \> 37.5 Celsius, as noted in patient diary |
Other
| Measure | Time frame | Description |
|---|---|---|
| Etiology of the upper respiratory tract infection at baseline | Day 1 | Identification of the viral or bacterial pathogen responsible for the baseline episode of upper respiratory tract infection by molecular methods |
| Salivary vitamin D at baseline | Day 1 | Concentration of vitamin D at baseline as measured in saliva sample |
Countries
Mexico
Outcome results
None listed