Acute Respiratory Tract InfectionsNCT05378022
Effects of Nasal-spraying LiveSpo Navax in Treatment of Influenza Virus in Children
A study testing LiveSpo Navax and 0.9% NaCl physiological saline in people with Acute Respiratory Tract Infections, run by National Children's Hospital, Vietnam at 1 site in Vietnam.
Trial summary
Acute Respiratory Tract Infections (ARTIs) in children are common diseases, with influenza virus types A and B is one of the main causes of serious symptoms in young children. Although an influenza vaccine is available, influenza vaccination requires annual injections, which made it difficult for young children to get… Read more about this study
- Who is it for?
- Ages 4 months to 7 years
- Conditions the study is for
- Acute Respiratory Tract Infections
- What is being tested?
- LiveSpo Navax and 0.9% NaCl physiological saline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteVietnam
- Study dates
- 21 Dec 2020to 22 Apr 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 months to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children (male/female) aged from 4 months to 7 years
- Admitted to hospital due to upper respiratory infection
- Influenza A and B positive by rapid test
- Parents of the pediatric patient agree to participate in the study, explain and sign the research consent form.
Who cannot join
- Newborn babies
- Having a history of drug allergies
- Need oxygen therapy
- Discharged before day 2
- Lost to follow-up
- Withdrawn from the trial
- Continuing in the trial but missing data
- Meeting the criteria for psychiatric disorders other than depression and/or anxiety.
Trial locations and contacts
1 site in 1 country.
Vietnam1 site
International Center, Vietnam National Children's Hospital
Hanoi, 100000
About this study
Official title: Application of LiveSpo Navax in Treatment of Acute Respiratory Disease in Children Infected With Influenza Virus
Acute Respiratory Tract Infections (ARTIs) in children are common diseases, with influenza virus types A and B is one of the main causes of serious symptoms in young children. Although an influenza vaccine is available, influenza vaccination requires annual injections, which made it difficult for young children to get effectively immunized. Moreover, antiviral nucleotide drugs including Tamiflu (oseltamivir) are unsafe for young children and are recommended only for high-risk patients. Probiotics have emerged as promising safe candidates for supportive treatment of ARTIs and reduction of antibiotic dependence in recent years. Here, investigators propose that direct spraying of probiotics into the nose can be a fast and effective symptomatic treatment for ARTIs due to influenza virus.
The aim of the study about to evaluate the effectiveness of nasal-spraying probiotics containing spores of two bacterial strains, Bacillus subtilis and Bacillus clausii in preventing and supporting the treatment of children having acute respiratory symptoms due to influenza infection.
Read more
Study Population: sample size is 70. Description of Sites: the study is carried out at Vietnam National Children's Hospital.
Description of Study Intervention: totally 70 eligible patients are divided randomly into 2 groups (n = 35/group each): Patients in Control group received the routine treatment and three times per day 0.9% NaCl physiological saline while the patients in the Navax group received three times per day LiveSpo Navax in addition to the same standard of care treatment. The standard treatment regimen is 2-5 days but can be extended further depending on the severity of the patient's respiratory failure.
Study duration: 15 months
Read the detailed description
Influenza virus types A and B is the common virus that causes Acute Respiratory Tract Infections (ARTIs) with a high risk of bronchiolitis for young children and infants. Influenza-infection symptoms range from mild fever, cough, runny nose, and wheezing to severe symptoms such as fast pulse, fast breathing, and respiratory failure. In a systematic review and meta-analysis of the global burden of seasonal influenza respiratory infections in young children, they estimated that 28.000 - 111.500 children under the age of 5 die as a result of influenza infections in 2008, of which 99% of these deaths occurred in developing countries. Influenza vaccination requires annual injections, which made it difficult for young children to get effectively immunized. Moreover, antiviral nucleotide drugs including Tamiflu (oseltamivir) are unsafe for young children and are recommended only for high-risk patients. Probiotics have emerged as promising safe candidates for supportive treatment of ARTIs and reduction of antibiotic dependence in recent years. However, the use of oral administrative probiotics as functional foods is effective only for mild symptoms and not applicable for Acute RTIs (ARTIs). Here, investigators propose that direct spraying of probiotics into the nose can be a fast and effective symptomatic treatment for ARTIs.
The objective was to investigate the symptomatic treatment effects of probiotic product LiveSpo Navax, as a liquid-suspension form containing Bacillus spores of safe B. subtilis ANA4 and B. clausii ANA39 strains, in children having acute respiratory diseases caused by influenza virus, investigators evaluation of improved efficacy and reduced treatment time of LiveSpo Navax in influenza-infected children; and measurement of changes in influenza viral load, co-infectious bacterial concentrations, and major cytokine indicators in the nasopharyngeal samples before and after 2 days using LiveSpo Navax.
Methods: A randomized, blind, and controlled clinical trial is conducted. The patient's parents are required to provide the following information about their children: full name, sex, age, obstetric history, vaccination history, and antibiotic use history… After informed consent, 70 patients with ARTIs due to influenza virus will be randomized into 2 groups (n = 35/group): the control group (named "Control" group) uses 0.9% NaCl physiological saline and an experimental group (named the "Navax" group) use the probiotics LiveSpo Navax. The patient is given a coded spray in the form of a blind sample to ensure the objectivity of the study. The clinical follow-up will be 5 days, nasopharyngeal samples will be collected at day 0 and day 2 to evaluate potential reductions in viral load and co-infection bacteria, as well as modulation of overreacted cytokine release and the presence of probiotic spores in the patient's nasal mucosa.
Real-time PCR for detection of microorganism in nasopharyngeal samples: semi-quantitative assays for measuring changes in influenza viral load and co-infection bacterial concentrations is conducted by the real-time RT-PCR/PCR routine protocol which has been standardized under ISO 15189:2012 criteria and used in Vietnam National Children's Hospital. Detection of B. subtilis ANA4 and B. clausii ANA39 are also conducted by real-time PCR SYBR Green that has been standardized under ISO 17025: 2017 standard and routinely in the Key Laboratory of Enzyme and Protein Technology, VNU University of Science.
ELISA assays for cytokine levels: pro-inflammatory cytokines levels (pg/mL) including interleukin (IL-6, IL-8) and TNF-alpha are quantified using an enzyme-linked immunosorbent assay kit (ELISA) according to the manufacturer's instructions.
During treatment, patients are monitored daily for typical clinical symptoms of Flu-induced respiratory tract infections, including runny nose, fever, dry rales, moist rales, body temperature (oC), oxymetry (SpO2) (%), pulse (beats/min), and breath (beats/min) until discharged. The patients' health conditions are observed by doctors and nurses, and their pieces of information are filled into medical records. During this study, parents' patients are asked to abstain from consumption for their children of other probiotics, either via nasal spray or oral administration, and refrain from cleaning nose for their children with other 0.9% NaCl physiological saline sprayers.
Data collection and statistical analysis: individual medical records are collected, and the patient's information is then gathered and systematized in a data set. The efficacy of LiveSpo Navax is evaluated and compared to 0.9% NaCl physiological saline based on the following clinical and sub-clinical criteria obtained in Navax and Control groups: (i) the symptomatic-relieving day; (ii) the reduction levels (2^△Ct) of influenza viral load and co-infection bacteria concentrations. △Ct for target genes is calculated as Ct (threshold cycle) at day 2 - Ct at day 0 while Ct of internal control is adjusted to be equal among all samples; (iii) the reduction levels of IL-6, IL-8, and TNF-alpha cytokines. The tabular analysis is performed on dichotomous variables using the χ2 test or Fisher's exact test when the expected value of any cell is below five. Continuous variables are compared using either the Wilcoxon test, t-test, or the Mann-Whitney test when data are not normally distributed. The correlations among the variables are assessed by Spearman's correlation analysis. Statistical and graphical analyses are performed on GraphPad Prism v8.4.3 software (GraphPad Software, CA, USA). The significance level of all analyzes is set at p < 0.05. P-values.
Expected outcomes: (i) LiveSpo Navax alleviates influenza-infection symptoms about 30% more effectively, as indicated by 90% of patients using LiveSpo Navax (Navax group) are symptom-free at day 2-5 of intervention depending on symptoms, compared to 60% of patients in Control group; (ii) Patients in Navax group has more significant reductions in influenza viral load (>10 fold) than patients in Control group at day 2 of intervention.
- Conditions
- Acute Respiratory Tract Infections
- Being tested
- LiveSpo Navax, 0.9% NaCl physiological saline
- Keywords
- Influenza Virus (Flu), Acute Respiratory Tract Infections (ARTIs), Children, Nasal-spraying probiotics, Viral load, Co-infection bacteria, Cytokines, Bacillus spores
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiveSpo NavaxCombination product
Also called Registration number: No.210001337/PCBA-HN
In Vietnam, LiveSpo Navax is manufactured as a Class-A medical device product (Product declaration No.210001337/PCBA-HN) under manufacturing standards approved by Hanoi Health Department, Ministry of Health, Vietnam (Certificate No YT117-19) and ISO 13485:2016.
0.9% NaCl physiological salineDrug
Also called Registration number: VD-32723-19
Nasal-spraying 0.9% NaCl physiological saline is prepared by extracting 5 mL from 0.9% NaCl intravenous infusion 500 mL PP bottle (B.Braun, Germany, product declaration No. VD-32732-19), and then pouring it into the same opaque plastic spraying 10 mL-bottle that is used for LiveSpo Navax.
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Control group receives the routine treatment and uses 0.9% NaCl physiological saline:
Routine treatment is as follows:
* Oral administrative drugs: antipyretic paracetamol (Efferegant®); expectorant Carbocysteine (Carbothiol®); antiviral Oseltamivir phosphate (Tamiflu®); antibiotics e.g. cefotaxim (Goldcefo®), Amoxicillin / clavulanic acid (Augmentin®) based on the results of antibiotic susceptibility test.
* Aerosol therapy: bronchodilator e.g. salbutamol (Ventolin ®️inhaler) or budesonide (Pulmicort ®️Respules). Receives: Drug: 0.9% NaCl physiological saline |
| Navax | Experimental | Navax group receives the routine treatment and uses NaCl 0.9% plus B. subtilis and B. clausii at 5 billion CFU/5 mL (LiveSpo®️ Navax):
Routine treatment is as follows:
Oral administrative drugs: antipyretic paracetamol (Efferegant®); expectorant Carbocysteine (Carbothiol®); antiviral Oseltamivir phosphate (Tamiflu®); antibiotics e.g. cefotaxime (Goldcefo®), Amoxicillin / clavulanic acid (Augmentin®) based on the results of antibiotic susceptibility test.
- Aerosol therapy: bronchodilator e.g. salbutamol (Ventolin ®️inhaler) or budesonide (Pulmicort ®️Respules). Receives: Combination Product: LiveSpo Navax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with free respiratory symptoms
Percentage (%) of influenza-infected patients with free respiratory symptoms including runny nose, fever, dry rales, moist rales, fast breath, and fast pulse
Measured: Day 0 to day 5
Secondary outcomes (7)
Patient's breath
Influenza-infected patient's breath (beats/min) before and after nasal-spraying
Measured: Day 0 to day 5
Patient's pulse
Influenza-infected patient's pulse (beats/min) before and after nasal-spraying
Measured: Day 0 and day 5
Patient's temperature
Influenza-infected patient's temperature (oC) before and after nasal-spraying
Measured: Day 0 and day 5
Patient's pulse oxygen (SpO2)
Influenza-infected patient's pulse oxygen-SpO2 (%) before and after nasal-spraying
Measured: Day 0 to day 5
Influenza virus concentration
Concentration of influenza virus in nasopharyngeal samples, as indicated by real-time RT-PCR threshold cycle (Ct) value
Measured: Day 0 and day 2
Co-infection bacterial concentrations
Co-infection bacterial concentrations in nasopharyngeal samples, as indicated by real time PCR threshold cycle (Ct) values
Measured: Day 0 and day 2
Cytokines levels
Levels (pg/mL) of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) in nasopharyngeal samples
Measured: Day 0 and day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start21 Dec 2020
- Primary completion31 Mar 2022
- Study completion22 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Tract InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Blind, randomized, and controlled clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Children's Hospital, Vietnam
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tran Thanh Tu, National Children's Hospital, Vietnam
- Investigators
- Tu T Tran, PhD. MD., Principal investigator, International Center, Vietnam National Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05378022
- Sponsor's protocol ID
- 2020S-06.2
- Other IDs
- No. 441/BVNTW-VNCSKTE
- Status last verified
- May 2022
- First submitted
- 12 May 2022
- Last updated
- 24 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data or samples share that will be coded, with no PHI include. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.
Publications
Doyle JD, Campbell AP. Pediatric influenza and illness severity: what is known and what questions remain? Curr Opin Pediatr. 2019 Feb;31(1):119-126. doi: 10.1097/MOP.0000000000000721.
PubMed 30531402Sellers SA, Hagan RS, Hayden FG, Fischer WA 2nd. The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017 Sep;11(5):372-393. doi: 10.1111/irv.12470.
PubMed 28745014Dawood FS, Chaves SS, Perez A, Reingold A, Meek J, Farley MM, Ryan P, Lynfield R, Morin C, Baumbach J, Bennett NM, Zansky S, Thomas A, Lindegren ML, Schaffner W, Finelli L; Emerging Infections Program Network. Complications and associated bacterial coinfections among children hospitalized with seasonal or pandemic influenza, United States, 2003-2010. J Infect Dis. 2014 Mar 1;209(5):686-94. doi: 10.1093/infdis/jit473. Epub 2013 Aug 28.
PubMed 23986545Eccles R. Understanding the symptoms of the common cold and influenza. Lancet Infect Dis. 2005 Nov;5(11):718-25. doi: 10.1016/S1473-3099(05)70270-X.
PubMed 16253889COMMITTEE ON INFECTIOUS DISEASES. Recommendations for Prevention and Control of Influenza in Children, 2021-2022. Pediatrics. 2021 Oct;148(4):e2021053745. doi: 10.1542/peds.2021-053745. Epub 2021 Sep 7.
PubMed 34493538Bustinduy AL, Sutherland LJ, Chang-Cojulun A, Malhotra I, DuVall AS, Fairley JK, Mungai PL, Muchiri EM, Mutuku FM, Kitron U, King CH. Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-alpha Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections. Am J Trop Med Hyg. 2015 May;92(5):945-51. doi: 10.4269/ajtmh.14-0444. Epub 2015 Mar 9.
PubMed 25758654Diaz PV, Valdivia G, Gaggero AA, Bono MR, Zepeda G, Rivas M, Uasapud P, Pinto RA, Boza ML, Guerrero J. Pro-Inflammatory Cytokines in Nasopharyngeal Aspirate From Hospitalized Children With Respiratory Syncytial Virus Infection With or Without Rhinovirus Bronchiolitis, and Use of the Cytokines as Predictors of Illness Severity. Medicine (Baltimore). 2015 Sep;94(39):e1512. doi: 10.1097/MD.0000000000001512.
PubMed 26426613Duvigneau S, Sharma-Chawla N, Boianelli A, Stegemann-Koniszewski S, Nguyen VK, Bruder D, Hernandez-Vargas EA. Hierarchical effects of pro-inflammatory cytokines on the post-influenza susceptibility to pneumococcal coinfection. Sci Rep. 2016 Nov 22;6:37045. doi: 10.1038/srep37045.
PubMed 27872472Vazquez Y, Gonzalez L, Noguera L, Gonzalez PA, Riedel CA, Bertrand P, Bueno SM. Cytokines in the Respiratory Airway as Biomarkers of Severity and Prognosis for Respiratory Syncytial Virus Infection: An Update. Front Immunol. 2019 Jun 4;10:1154. doi: 10.3389/fimmu.2019.01154. eCollection 2019.
PubMed 31214165Pandolfi E, Panera N, Alisi A, Carloni E, Russo L, Campagna I, Rizzo C, Concato C, Linardos G, Piccioni L, Jackson S, Villani A, Midulla F, Tozzi AE. Cytokine expression patterns in hospitalized children with Bordetella pertussis, Rhinovirus or co-infection. Sci Rep. 2021 May 26;11(1):10948. doi: 10.1038/s41598-021-89538-0.
PubMed 34040002Hu W, DeMarcus LS, Sjoberg PA, Robbins AS. Inactivated influenza vaccine effectiveness among department of defense beneficiaries aged 6 months-17 years, 2016-2017 through 2019-2020 influenza seasons. PLoS One. 2021 Aug 27;16(8):e0256165. doi: 10.1371/journal.pone.0256165. eCollection 2021.
PubMed 34450617Smith JR, Ariano RE, Toovey S. The use of antiviral agents for the management of severe influenza. Crit Care Med. 2010 Apr;38(4 Suppl):e43-51. doi: 10.1097/CCM.0b013e3181c85229.
PubMed 19935416Sugaya N, Tamura D, Yamazaki M, Ichikawa M, Kawakami C, Kawaoka Y, Mitamura K. Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children. Clin Infect Dis. 2008 Aug 1;47(3):339-45. doi: 10.1086/589748.
PubMed 18582202American Academy of Pediatrics Committee on Infectious Diseases. Antiviral therapy and prophylaxis for influenza in children. Pediatrics. 2007 Apr;119(4):852-60. doi: 10.1542/peds.2007-0224.
PubMed 17403862Nicholson KG, Aoki FY, Osterhaus AD, Trottier S, Carewicz O, Mercier CH, Rode A, Kinnersley N, Ward P. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet. 2000 May 27;355(9218):1845-50. doi: 10.1016/s0140-6736(00)02288-1.
PubMed 10866439
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of LiveSpo Navax in Treatment of Acute Respiratory Disease in Children Infected With Influenza Virus
- ClinicalTrials.gov ID
- NCT05378022
- Acronym / sponsor ID
- 2020S-06.2
- Conditions
- Acute Respiratory Tract Infections
- Keywords
- Influenza Virus (Flu), Acute Respiratory Tract Infections (ARTIs), Children, Nasal-spraying probiotics, Viral load, Co-infection bacteria, Cytokines, Bacillus spores
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- National Children's Hospital, VietnamUniversity, hospital or other
- Study start
- 21 Dec 2020 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 22 Apr 2022 (actual)
- First posted
- 17 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute Respiratory Tract Infections (ARTIs) in children are common diseases, with influenza virus types A and B is one of the main causes of serious symptoms in young children. Although an influenza vaccine is available, influenza vaccination requires annual injections, which made it difficult for young children to get effectively immunized. Moreover, antiviral nucleotide drugs including Tamiflu (oseltamivir) are unsafe for young children and are recommended only for high-risk patients. Probiotics have emerged as promising safe candidates for supportive treatment of ARTIs and reduction of antibiotic dependence in recent years. Here, investigators propose that direct spraying of probiotics into the nose can be a fast and effective symptomatic treatment for ARTIs due to influenza virus.
The aim of the study about to evaluate the effectiveness of nasal-spraying probiotics containing spores of two bacterial strains, Bacillus subtilis and Bacillus clausii in preventing and supporting the treatment of children having acute respiratory symptoms due to influenza infection.
Study Population: sample size is 70. Description of Sites: the study is carried out at Vietnam National Children's Hospital.
Description of Study Intervention: totally 70 eligible patients are divided randomly into 2 groups (n = 35/group each): Patients in Control group received the routine treatment and three times per day 0.9% NaCl physiological saline while the patients in the Navax group received three times per day LiveSpo Navax in addition to the same standard of care treatment. The standard treatment regimen is 2-5 days but can be extended further depending on the severity of the patient's respiratory failure.
Study duration: 15 months
Detailed description
Influenza virus types A and B is the common virus that causes Acute Respiratory Tract Infections (ARTIs) with a high risk of bronchiolitis for young children and infants. Influenza-infection symptoms range from mild fever, cough, runny nose, and wheezing to severe symptoms such as fast pulse, fast breathing, and respiratory failure. In a systematic review and meta-analysis of the global burden of seasonal influenza respiratory infections in young children, they estimated that 28.000 - 111.500 children under the age of 5 die as a result of influenza infections in 2008, of which 99% of these deaths occurred in developing countries. Influenza vaccination requires annual injections, which made it difficult for young children to get effectively immunized. Moreover, antiviral nucleotide drugs including Tamiflu (oseltamivir) are unsafe for young children and are recommended only for high-risk patients. Probiotics have emerged as promising safe candidates for supportive treatment of ARTIs and reduction of antibiotic dependence in recent years. However, the use of oral administrative probiotics as functional foods is effective only for mild symptoms and not applicable for Acute RTIs (ARTIs). Here, investigators propose that direct spraying of probiotics into the nose can be a fast and effective symptomatic treatment for ARTIs.
The objective was to investigate the symptomatic treatment effects of probiotic product LiveSpo Navax, as a liquid-suspension form containing Bacillus spores of safe B. subtilis ANA4 and B. clausii ANA39 strains, in children having acute respiratory diseases caused by influenza virus, investigators evaluation of improved efficacy and reduced treatment time of LiveSpo Navax in influenza-infected children; and measurement of changes in influenza viral load, co-infectious bacterial concentrations, and major cytokine indicators in the nasopharyngeal samples before and after 2 days using LiveSpo Navax.
Methods: A randomized, blind, and controlled clinical trial is conducted. The patient's parents are required to provide the following information about their children: full name, sex, age, obstetric history, vaccination history, and antibiotic use history… After informed consent, 70 patients with ARTIs due to influenza virus will be randomized into 2 groups (n = 35/group): the control group (named "Control" group) uses 0.9% NaCl physiological saline and an experimental group (named the "Navax" group) use the probiotics LiveSpo Navax. The patient is given a coded spray in the form of a blind sample to ensure the objectivity of the study. The clinical follow-up will be 5 days, nasopharyngeal samples will be collected at day 0 and day 2 to evaluate potential reductions in viral load and co-infection bacteria, as well as modulation of overreacted cytokine release and the presence of probiotic spores in the patient's nasal mucosa.
Real-time PCR for detection of microorganism in nasopharyngeal samples: semi-quantitative assays for measuring changes in influenza viral load and co-infection bacterial concentrations is conducted by the real-time RT-PCR/PCR routine protocol which has been standardized under ISO 15189:2012 criteria and used in Vietnam National Children's Hospital. Detection of B. subtilis ANA4 and B. clausii ANA39 are also conducted by real-time PCR SYBR Green that has been standardized under ISO 17025: 2017 standard and routinely in the Key Laboratory of Enzyme and Protein Technology, VNU University of Science.
ELISA assays for cytokine levels: pro-inflammatory cytokines levels (pg/mL) including interleukin (IL-6, IL-8) and TNF-alpha are quantified using an enzyme-linked immunosorbent assay kit (ELISA) according to the manufacturer's instructions.
During treatment, patients are monitored daily for typical clinical symptoms of Flu-induced respiratory tract infections, including runny nose, fever, dry rales, moist rales, body temperature (oC), oxymetry (SpO2) (%), pulse (beats/min), and breath (beats/min) until discharged. The patients' health conditions are observed by doctors and nurses, and their pieces of information are filled into medical records. During this study, parents' patients are asked to abstain from consumption for their children of other probiotics, either via nasal spray or oral administration, and refrain from cleaning nose for their children with other 0.9% NaCl physiological saline sprayers.
Data collection and statistical analysis: individual medical records are collected, and the patient's information is then gathered and systematized in a data set. The efficacy of LiveSpo Navax is evaluated and compared to 0.9% NaCl physiological saline based on the following clinical and sub-clinical criteria obtained in Navax and Control groups: (i) the symptomatic-relieving day; (ii) the reduction levels (2^△Ct) of influenza viral load and co-infection bacteria concentrations. △Ct for target genes is calculated as Ct (threshold cycle) at day 2 - Ct at day 0 while Ct of internal control is adjusted to be equal among all samples; (iii) the reduction levels of IL-6, IL-8, and TNF-alpha cytokines. The tabular analysis is performed on dichotomous variables using the χ2 test or Fisher's exact test when the expected value of any cell is below five. Continuous variables are compared using either the Wilcoxon test, t-test, or the Mann-Whitney test when data are not normally distributed. The correlations among the variables are assessed by Spearman's correlation analysis. Statistical and graphical analyses are performed on GraphPad Prism v8.4.3 software (GraphPad Software, CA, USA). The significance level of all analyzes is set at p < 0.05. P-values.
Expected outcomes: (i) LiveSpo Navax alleviates influenza-infection symptoms about 30% more effectively, as indicated by 90% of patients using LiveSpo Navax (Navax group) are symptom-free at day 2-5 of intervention depending on symptoms, compared to 60% of patients in Control group; (ii) Patients in Navax group has more significant reductions in influenza viral load (>10 fold) than patients in Control group at day 2 of intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Blind, randomized, and controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: 0.9% NaCl physiological salineControl group receives the routine treatment and uses 0.9% NaCl physiological saline: Routine treatment is as follows: * Oral administrative drugs: antipyretic paracetamol (Efferegant®); expectorant Carbocysteine (Carbothiol®); antiviral Oseltamivir phosphate (Tamiflu®); antibiotics e.g. cefotaxim (Goldcefo®), Amoxicillin / clavulanic acid (Augmentin®) based on the results of antibiotic susceptibility test. * Aerosol therapy: bronchodilator e.g. salbutamol (Ventolin ®️inhaler) or budesonide (Pulmicort ®️Respules). |
| Navax | Experimental | Combination Product: LiveSpo NavaxNavax group receives the routine treatment and uses NaCl 0.9% plus B. subtilis and B. clausii at 5 billion CFU/5 mL (LiveSpo®️ Navax): Routine treatment is as follows: Oral administrative drugs: antipyretic paracetamol (Efferegant®); expectorant Carbocysteine (Carbothiol®); antiviral Oseltamivir phosphate (Tamiflu®); antibiotics e.g. cefotaxime (Goldcefo®), Amoxicillin / clavulanic acid (Augmentin®) based on the results of antibiotic susceptibility test. - Aerosol therapy: bronchodilator e.g. salbutamol (Ventolin ®️inhaler) or budesonide (Pulmicort ®️Respules). |
Who may qualify
- Ages
- 4 months to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Children (male/female) aged from 4 months to 7 years
- Admitted to hospital due to upper respiratory infection
- Influenza A and B positive by rapid test
- Parents of the pediatric patient agree to participate in the study, explain and sign the research consent form.
Key exclusion criteria (8 listed)
- Newborn babies
- Having a history of drug allergies
- Need oxygen therapy
- Discharged before day 2
- Lost to follow-up
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiveSpo NavaxAlso: Registration number: No.210001337/PCBA-HNIn Vietnam, LiveSpo Navax is manufactured as a Class-A medical device product (Product declaration No.210001337/PCBA-HN) under manufacturing standards approved by Hanoi Health Department, Ministry of Health, Vietnam (Certificate No YT117-19) and ISO 13485:2016. | Combination product | Navax |
| 0.9% NaCl physiological salineAlso: Registration number: VD-32723-19Nasal-spraying 0.9% NaCl physiological saline is prepared by extracting 5 mL from 0.9% NaCl intravenous infusion 500 mL PP bottle (B.Braun, Germany, product declaration No. VD-32732-19), and then pouring it into the same opaque plastic spraying 10 mL-bottle that is used for LiveSpo Navax. | Drug | Control |
Primary outcome
Percentage of patients with free respiratory symptoms
Time frame: Day 0 to day 5
Percentage (%) of influenza-infected patients with free respiratory symptoms including runny nose, fever, dry rales, moist rales, fast breath, and fast pulse
7 secondary outcomes
Patient's breath
Time frame: Day 0 to day 5
Patient's pulse
Time frame: Day 0 and day 5
Patient's temperature
Time frame: Day 0 and day 5
Patient's pulse oxygen (SpO2)
Time frame: Day 0 to day 5
Influenza virus concentration
Time frame: Day 0 and day 2
Co-infection bacterial concentrations
Time frame: Day 0 and day 2
Cytokines levels
Time frame: Day 0 and day 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2022.
- Background: PubMed 30531402Doyle JD, Campbell AP. Pediatric influenza and illness severity: what is known and what questions remain? Curr Opin Pediatr. 2019 Feb;31(1):119-126. doi: 10.1097/MOP.0000000000000721.
- Background: PubMed 28745014Sellers SA, Hagan RS, Hayden FG, Fischer WA 2nd. The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017 Sep;11(5):372-393. doi: 10.1111/irv.12470.
- Background: PubMed 23986545Dawood FS, Chaves SS, Perez A, Reingold A, Meek J, Farley MM, Ryan P, Lynfield R, Morin C, Baumbach J, Bennett NM, Zansky S, Thomas A, Lindegren ML, Schaffner W, Finelli L; Emerging Infections Program Network. Complications and associated bacterial coinfections among children hospitalized with seasonal or pandemic influenza, United States, 2003-2010. J Infect Dis. 2014 Mar 1;209(5):686-94. doi: 10.1093/infdis/jit473. Epub 2013 Aug 28.
- Background: PubMed 16253889Eccles R. Understanding the symptoms of the common cold and influenza. Lancet Infect Dis. 2005 Nov;5(11):718-25. doi: 10.1016/S1473-3099(05)70270-X.
- Background: PubMed 34493538COMMITTEE ON INFECTIOUS DISEASES. Recommendations for Prevention and Control of Influenza in Children, 2021-2022. Pediatrics. 2021 Oct;148(4):e2021053745. doi: 10.1542/peds.2021-053745. Epub 2021 Sep 7.
- Background: PubMed 25758654Bustinduy AL, Sutherland LJ, Chang-Cojulun A, Malhotra I, DuVall AS, Fairley JK, Mungai PL, Muchiri EM, Mutuku FM, Kitron U, King CH. Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-alpha Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections. Am J Trop Med Hyg. 2015 May;92(5):945-51. doi: 10.4269/ajtmh.14-0444. Epub 2015 Mar 9.
- Background: PubMed 26426613Diaz PV, Valdivia G, Gaggero AA, Bono MR, Zepeda G, Rivas M, Uasapud P, Pinto RA, Boza ML, Guerrero J. Pro-Inflammatory Cytokines in Nasopharyngeal Aspirate From Hospitalized Children With Respiratory Syncytial Virus Infection With or Without Rhinovirus Bronchiolitis, and Use of the Cytokines as Predictors of Illness Severity. Medicine (Baltimore). 2015 Sep;94(39):e1512. doi: 10.1097/MD.0000000000001512.
- Background: PubMed 27872472Duvigneau S, Sharma-Chawla N, Boianelli A, Stegemann-Koniszewski S, Nguyen VK, Bruder D, Hernandez-Vargas EA. Hierarchical effects of pro-inflammatory cytokines on the post-influenza susceptibility to pneumococcal coinfection. Sci Rep. 2016 Nov 22;6:37045. doi: 10.1038/srep37045.
- Background: PubMed 31214165Vazquez Y, Gonzalez L, Noguera L, Gonzalez PA, Riedel CA, Bertrand P, Bueno SM. Cytokines in the Respiratory Airway as Biomarkers of Severity and Prognosis for Respiratory Syncytial Virus Infection: An Update. Front Immunol. 2019 Jun 4;10:1154. doi: 10.3389/fimmu.2019.01154. eCollection 2019.
- Background: PubMed 34040002Pandolfi E, Panera N, Alisi A, Carloni E, Russo L, Campagna I, Rizzo C, Concato C, Linardos G, Piccioni L, Jackson S, Villani A, Midulla F, Tozzi AE. Cytokine expression patterns in hospitalized children with Bordetella pertussis, Rhinovirus or co-infection. Sci Rep. 2021 May 26;11(1):10948. doi: 10.1038/s41598-021-89538-0.
- Background: PubMed 34450617Hu W, DeMarcus LS, Sjoberg PA, Robbins AS. Inactivated influenza vaccine effectiveness among department of defense beneficiaries aged 6 months-17 years, 2016-2017 through 2019-2020 influenza seasons. PLoS One. 2021 Aug 27;16(8):e0256165. doi: 10.1371/journal.pone.0256165. eCollection 2021.
- Background: PubMed 19935416Smith JR, Ariano RE, Toovey S. The use of antiviral agents for the management of severe influenza. Crit Care Med. 2010 Apr;38(4 Suppl):e43-51. doi: 10.1097/CCM.0b013e3181c85229.
- Individual participant dataSharing planned: Yes. Data or samples share that will be coded, with no PHI include. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tu T Tran, PhD. MD. principal investigator
International Center, Vietnam National Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LiveSpo Navax and 0.9% NaCl physiological saline in people with Acute Respiratory Tract Infections, run by National Children's Hospital, Vietnam at 1 site in Vietnam.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with free respiratory symptoms (time frame: Day 0 to day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05378022, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2022.