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Efficacy and Safety of L. Plantarum and P. Acidilactici in Children With Upper Respiratory Tract Infections

Not Applicable
Terminated
Conditions
Pharyngitis
Upper Respiratory Tract Infections
Tonsillitis
Interventions
Other: Placebo
Dietary Supplement: Probiotic
Registration Number
NCT05279534
Lead Sponsor
AB Biotics, SA
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
80
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlPlaceboThe control study product is identical in packaging and formulation except that none of strains Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485 and Pediococcus acidilactici CECT7483 (probiotic bacteria) are present. The Control product contains maltodextrin (E1400, qs) only, in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0.
ProbioticProbioticActive test product contains four lactic acid bacteria strains with Qualified Presumption of Safety (QPS) status by European Food Safety Authority (EFSA): Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and Pediococcus acidilactici CECT7483, with maltodextrin (E1400, qs) as excipient, formulated in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0. Active test product is a food supplement and not an investigational medicinal product
Primary Outcome Measures
NameTimeMethod
Daily evolution of feverDay 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

Daily evolution of painDay 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

Secondary Outcome Measures
NameTimeMethod
Change in microbiotaDay 1 to 15

Change in microbiota composition, as determined by 16S gene sequencing

Time to complete symptom resolutionDay 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 recurrenceDay 15 to 60

Time to body temperature \>37.5 Celsius after initial resolution (see outcome #19), as noted in patient diary

Time to pain recurrenceDay 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

Days with coughDay 1 to 60

Days of cough, as noted in patient diary

Change in salivary immune biomarkersDay 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

Days with nasal congestionDay 1 to 60

Days of nasal congestion, as noted in patient diary

Number of hospitalizationsDay 1 to 60

Number of children being hospitalized related to respiratory tract infection

Number of medical or emergency visitsDay 1 to 60

Number of medical or emergency visits related to respiratory tract infection

Time to fever resolutionDay 1 to 15

Time to body temperature at or below 37.5 Celsius, as noted in patient diary

Time to any symptom recurrenceDay 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

Total treatment costsDay 1 to 60

Cost of medical and emergency visits, drug treatments (anti-inflammatory drugs, anti-histamines and antibiotics) and schooling absence

Fever Area Under the CurveDay 1 to 60

Area Under the Curve (AUC) of daily fever (body temperature, Celsius degrees)

Pain Area Under the CurveDay 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 feverDay 1 to 60

Days with body temperature \> 37.5 Celsius, as noted in patient diary

Days with painDay 1 to 60

Days with pain as per FLACC scale (Face, Legs, Activity, Cry and Consolability), as noted in patient diary

Days with rhinorrheaDay 1 to 60

Days with runny nose, as noted in patient diary

Days with any symptomDay 1 to 60

Days with one or more of the following symptom: fever, pain, rhinorrhea, cough or nasal congestion (as noted in patient diary)

Time to pain resolutionDay 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

Days with concomitant medicationDay 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 antibioticsDay 1 to 60

Number of children receiving antibiotics

Days of schooling absenceDay 1 to 60

Days of daycare or kindergarten absence, as noted in patient diary

Trial Locations

Locations (1)

Hospital General Dr. Manuel Gea Gonzalez

🇲🇽

Mexico City, Mexico DF, Mexico

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