Clinical trial NCT05279534: Efficacy and Safety of L. Plantarum and P. Acidilactici in Children With Upper Respiratory Tract Infections
Official title: Efficacy and Safety of Lactobacillus Plantarum and Pediococcus Acidilactici as Twice-daily Co-adjuvant Therapy of Upper Respiratory Tract Infections in Children 6 Months to 5 Years Old
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Upper Respiratory Tract Infections
Pharyngitis
Tonsillitis
Keywords: Probiotic
Lead sponsor: AB Biotics, SA
Sponsor class: INDUSTRY
Collaborators: name: Innovacion y Desarrollo de Estrategias en Salud
name: Hospital General Dr. Manuel Gea González
First posted: 2022-03-15
Enrollment: 80
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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)
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Daily evolution of fever
timeFrame: Day 1 to 15
measure: Daily evolution of pain
timeFrame: Day 1 to 15
Secondary outcomes:
measure: Fever Area Under the Curve
timeFrame: Day 1 to 60
measure: Pain Area Under the Curve
timeFrame: Day 1 to 60
measure: Days with fever
timeFrame: Day 1 to 60
measure: Days with pain
timeFrame: Day 1 to 60
measure: Days with rhinorrhea
timeFrame: Day 1 to 60
measure: Days with cough
timeFrame: Day 1 to 60
measure: Days with nasal congestion
timeFrame: Day 1 to 60
measure: Days with any symptom
timeFrame: Day 1 to 60
measure: Days with concomitant medication
timeFrame: Day 1 to 60
measure: Number of children receiving antibiotics
timeFrame: Day 1 to 60
measure: Number of hospitalizations
timeFrame: Day 1 to 60
measure: Number of medical or emergency visits
timeFrame: Day 1 to 60
measure: Days of schooling absence
timeFrame: Day 1 to 60
measure: Change in salivary immune biomarkers
timeFrame: Day 1 to 15
measure: Total treatment costs
timeFrame: Day 1 to 60
measure: Time to fever resolution
timeFrame: Day 1 to 15
measure: Time to pain resolution
timeFrame: Day 1 to 15
measure: Time to complete symptom resolution
timeFrame: Day 1 to 15
measure: Time to fever recurrence
timeFrame: Day 15 to 60
measure: Time to pain recurrence
timeFrame: Day 15 to 60
measure: Time to any symptom recurrence
timeFrame: Day 15 to 60
measure: Change in microbiota
timeFrame: Day 1 to 15
Other outcomes:
measure: Etiology of the upper respiratory tract infection at baseline
timeFrame: Day 1
measure: Salivary vitamin D at baseline
timeFrame: Day 1
Locations:
city: Mexico City
country: Mexico
facility: Hospital General Dr. Manuel Gea Gonzalez
state: Mexico DF
Study officials:
affiliation: Hospital General Dr. Manuel Gea Gonzalez
name: Pedro Gutierrez-Castrellon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Manworren RC, Hynan LS. Clinical validation of FLACC: preverbal patient pain scale. Pediatr Nurs. 2003 Mar-Apr;29(2):140-6.
citation: Gutierrez-Castrellon P, Gandara-Marti T, Abreu Y Abreu AT, Nieto-Rufino CD, Lopez-Orduna E, Jimenez-Escobar I, Jimenez-Gutierrez C, Lopez-Velazquez G, Espadaler-Mazo J. Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial. Gut Microbes. 2022 Jan-Dec;14(1):2018899. doi: 10.1080/19490976.2021.2018899.
citation: Maya-Barrios A, Lira-Hernandez K, Jimenez-Escobar I, Hernandez L, Ortiz-Hernandez A, Jimenez-Gutierrez C, Lopez-Velazquez G, Gutierrez-Castrellon P. Limosilactobacillus reuteri ATCC PTA 5289 and DSM 17938 as adjuvants to improve evolution of pharyngitis/tonsillitis in children: randomised controlled trial. Benef Microbes. 2021 Apr 12;12(2):137-145. doi: 10.3920/BM2020.0171. Epub 2021 Apr 1.
citation: Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997 May-Jun;23(3):293-7.