Efficacy and safety of a probiotic supplement containing L. plantarum and P. acidilactici strains in young children with common respiratory viral infections

ISRCTN	ISRCTN66122782
DOI	https://doi.org/10.1186/ISRCTN66122782
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	RESPIKIDS-II
Sponsor	AB-BIOTICS SA (KANEKA Corp.)
Funder	AB-BIOTICS SA (KANEKA Corp.)

Submission date: 04/10/2023
Registration date: 05/10/2023
Last edited: 28/08/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Uncomplicated upper respiratory infections are common in children and typically caused by viruses. Previous studies have shown intake of some probiotics can reduce the duration of such respiratory infections in children, when taken in a preventive manner. The aim of this study is to determine if a particular probiotic formula can reduce the duration of symptoms when taken after the onset of such respiratory infections in children.

Who can participate?
Infants and children, 6 months to 5 years old, with an upper respiratory infection with fever and throat pain (pharyngitis), whose symptoms are of likely viral origin, as per doctor's judgment.

What does the study involve?
Eligible children are randomly allocated to receive either the specific probiotic formula (containing strains L. plantarum KABP033, KABP023 and KABP022 and P. acidilactici KABP021) in capsules, or identically-looking placebo capsules, twice daily. Study subjects can also receive standard of care treatment, at study investigators discretion, consisting of ibuprofen (an approved anti-inflammatory drug) and/or cetirizine (an approved anti-histaminic drug).

Parents or caregivers are taught to rate their children's pain using a visual scale (the FLACC scale). Parents or caregivers are instructed to fill a daily diary with the observed FLACC score, as well as the highest body temperature, presence of runny nose (rhinorrhea), nasal congestion, cough, use of ibuprofen and use of cetirizine.

What are the possible benefits and risks of participating?
The probiotic strains used in this study were previously found to be safe, as well as effective at shortening the duration of fever and respiratory symptoms in a clinical trial in 300 Covid19 patients. Therefore, children who participate in this study could have the duration of the symptoms of their upper respiratory infection shortened. And if an adverse health event occured related to the participation in the study, the participants can reach the investigators anytime (24h availability by phone every day), and costs would be covered by an insurance already contracted by the study funder.

Where is the study run from?
Medica Sur Hospital, in Mexico City. (Mexico)

When is the study starting and how long is it expected to run for?
May 2023 to September 2024

Who is funding the study?
AB-BIOTICS SA (part of KANEKA Corporation) (Spain)

Who is the main contact?
Dr Diana Maria Andrade Platas, dianamandrade@yahoo.com

Contact information

Dr Diana M. Andrade Platas
Principal investigator

Hospital Medica Sur, Tower-II
Puente de Piedra No. 150 Colonia Toriello Guerra, Tlalpan
Mexico City
14050
Mexico

Phone	+52 55 3520 9755
Email	dianamandrade@yahoo.com

Dr Jordi Espadaler-Mazo
Public

AB-BIOTICS SA (KANEKA Corp.)
ESADE Creapolis, Av. Torre Blanca 57
Sant Cugat del Valles
08172
Spain

Phone	+34 902 90 38 44
Email	espadaler@ab-biotics.com

Dr Jordi Espadaler-Mazo
Scientific

AB-BIOTICS SA (KANEKA Corp.)
ESADE Creapolis, Av. Torre Blanca 57
Sant Cugat del Valles
08172
Spain

ORCID ID	0000-0002-0128-8363
Phone	+34 902 90 38 44
Email	espadaler@ab-biotics.com

Study information

Primary study design	Interventional
Study design	Randomized double-blind placebo-controlled parallel-group study
Secondary study design	Randomised parallel trial
Study type	Participant information sheet
Scientific title	Efficacy and safety of L. plantarum KABP033, KABP023 and KABP022 and P. acidilactici KABP021 in upper respiratory tract infections of viral origin in children aged 6 months to 5 years
Study objectives	The combination of probiotic strains L. plantarum KABP033, KABP023 and KABP022 and P. acidilactici KABP021, when taken twice daily, would reduce the duration of symptoms of upper respiratory tract infections of viral origin, compared to placebo.
Ethics approval(s)	Approved 22/09/2023, Commitee for Ethics and Research in Studies in Humans (Comité de Ética e Investigación para Estudios en Humanos (CEIEH)), Medica Sur Hospital (Puente de Piedra No. 150 Colonia Toriello Guerra, Tlalpan, Mexico City, 14050, Mexico; +52 55 5424 7200; comiteinvestigacion@medicasur.org.mx), ref: CB148-CEI153
Health condition(s) or problem(s) studied	Upper respiratory tract infections with pharyngitis, of likely viral origin, in children 6 months to 5 years old
Intervention	Using a centralised computer-based randomisation list, patients are randomised 1:1 to receive either probiotic capsules or indentical-looking placebo capsules, to be taken orally twice daily for 15 days (days 1 to 15 of the study). Randomisation list will be prepared by personnel not directly participating in the study and kept in a sealed enveloppe until study completion. Probiotic capsules contain Lactoplantibacillus plantarum strains KABP033, KABP023 and KABP022 and Pediococcus acidilactici strain KABP021, totaling 2 billion CFUs (colony-forming units) in a dextrin carrier. Placebo capsules contain dextrin carrier only. All capsules are made of hydroxymethyl-propyl-cellulose (HPMC) and are delivered in anonymous blisters, inside of anonymous boxes (30 capsules per box). Study subjects can also receive pediatric standard of care treatment, at study investigators discretion, consisting of ibuprofen suspension as anti-inflammatory drug (10mg per Kg of body weight per day) and/or cetirizine suspension as anti-histaminic drug (0.25mg per Kg of body weight per day). Finally, should study subjects develop infectious symptoms of likely bacterial origin after the study initiation, study investigators can prescribe antibiotic rescue medication at standard pediatric doses, consisting of amoxicillin clavulanate suspension (at 45mg per Kg of body weight per day), or clarythromycin suspension (at 7.5 mg per Kg of body weigh per day) if there is a history of allergy to penicillins.
Intervention type	Supplement
Primary outcome measure(s)	Numer of days with fever (body temperature >37.5ºC), as measured with a thermometer, and number of days with pain score >3, as measured with the FLACC score ("Face, Legs, Activity, Cry and Consolability"; Merkel et al. Pediatric Nursing 1997, 23:293-297), both recorded daily by parents in a diary from day 1 to 15 of intervention.
Key secondary outcome measure(s)	1. Area under the curve (AUC) of the FLACC score ("Face, Legs, Activity, Cry and Consolability"; Merkel et al. Pediatric Nursing 1997, 23:293-297), as recorded daily by parents in a diary from day 1 to 15 of intervention. 2. Area under the curve (AUC) of body temperature (in Celsius degrees), as recorded daily by parents in a diary from day 1 to 15 of intervention. 3. Etiological agent (using multiplex PCR for 16 respiratory viruses), as determined on nasopharyngeal swabs taken on day 0. 4. Metabolome analysis (polar and semi-polar metabolites, as analysed by HPLC-MS) of salivary samples taken on days 1 and 15. 5. Concentration of immunoglobulin A (IgA), TNF-alpha and interleukins 1b, 4, 6, 10, 17 and 18 in salivary samples taken on days 1 and 15. 6. Number of days with cough, as recorded daily by parents in a diary from day 1 to 15 of intervention. 7. Number of days with nasal congestion, as recorded daily by parents in a diary from day 1 to 15 of intervention. 8. Number of days with rhinorrhea, as recorded daily by parents in a diary from day 1 to 15 of intervention. 9. Number of days of intake of NSAIDs (ibuprofen), as recorded daily by parents in a diary from day 1 to 15 of intervention. 10. Number of days of intake of antihistaminics (cetirizine), as recorded daily by parents in a diary from day 1 to 15 of intervention. 11. Number of days of intake of antibiotics rescue medication, as recorded daily by parents in a diary from day 1 to 15 of intervention. 12. Number of medical or emergency visits, as recorded daily by parents in a diary from day 1 to 15 of intervention. 13. Number of medical or emergency visits after day 15, as recorded during face-to-face visits on days 30 and 60. 14. Number of different symptoms (of FLACC>3, fever >37.5ºC, presence of cough, rhinorrhea and nasal congestion), as recorded daily by parents in a diary from day 1 to 15 of intervention. 15. Number of different symptoms (of FLACC>3, fever >37.5ºC, presence of cough, rhinorrhea and nasal congestion), as recorded during face-to-face visits on days 30 and 60.
Completion date	20/09/2024

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Months
Upper age limit	5 Years
Sex	All
Target sample size at registration	90
Total final enrolment	75
Key inclusion criteria	1. Infants and children, 6 months to 5 years old, with upper respiratory infection of likely viral origin (based on investigator's judgment of symptoms) with pharyngitis. 2. Having a FLACC score ("Face, Legs, Activity, Cry and Consolability"; Merkel et al. Pediatric Nursing 1997, 23:293-297) > 3 and body temperature >37.5ºC. 3. Symptoms started within 48h of entry visit. 4. Written informed consent provided by parents or caregivers.
Key exclusion criteria	1. Tonsillitis, cervical lymphadenitis, otitis media or scarlatiniform rash (symptoms suggestive of bacterial infection). 2. Preterm infants or those having been born weighting <2500gr. 3. Failure to thrive 4. Use of antibiotics, antivirals or probiotics for more than 48h within 2 weeks of study entry. 5. Breastfed children whose mothers have taken antibiotics, antivirals or probiotics for more than 48h within 2 weeks of study entry. 6. History of two or more invasive infections (meningitis, osteomielitis, sepsis). 7. History of recurrent, severe respiratory infections within 12 months of study entry 8. Chronic diarrhea or gastroesophagic reflux disease (GERD). 9. Congenital heart, respiratory or digestive disease. 10. Primary or secondary immunodeficiency. 11. Asthma. 12. Any other condition that, according to the judgment of the principal investigator, warrants exclusion from the study
Date of first enrolment	14/10/2023
Date of final enrolment	15/12/2023

Locations

Countries of recruitment

Mexico

Study participating centre

Medica Sur Hospital

Puente de Piedra No. 150 Colonia Toriello Guerra, Tlalpan
Mexico City
14050
Mexico

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	After publication, individual anonymised participant data generated during and/or analysed during the current study will be available upon request from: Jordi Espadaler-Mazo, PhD. (espadaler@ab-biotics.com)

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

28/08/2024: The overall study end date was changed from 31/08/2024 to 20/09/2024.
11/06/2024: The following changes were made:
1. The overall study end date was changed from 20/06/2024 to 31/08/2024. September 20th
2. The intention to publish date was changed from 30/09/2024 to 31/12/2024.
09/04/2024: The following changes were made:
1. The overall study end date was changed from 30/04/2024 to 20/06/2024.
2. The intention to publish date was changed from 30/04/2025 to 30/09/2024.
03/04/2024: The public study contact was updated.
07/02/2024: The following changes were made to the trial record:
1. The total final enrolment was added.
2. The recruitment end date was changed from 28/02/2024 to 15/12/2023.
05/10/2023: Trial's existence confirmed by Committee for Ethics and Research in Studies in Humans (Comité de Ética e Investigación para Estudios en Humanos (CEIEH)), Medica Sur Hospital.