Effects of Nasal-spraying LiveSpo Navax in Treatment of Acute Respiratory Infections in Children
NCT ID: NCT05164692
Last Updated: 2021-12-21
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
COMPLETED
Clinical Phase
NA
Total Enrollment
100 participants
Study Classification
INTERVENTIONAL
Study Start Date
2020-08-29
Study Completion Date
2021-08-29
Brief Summary
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Rationals: Infection with the Respiratory Syncytial Virus (RSV) is one of the most common causes of respiratory tract diseases. However, treatment for pediatric RSV infection remains supportive to prevent co-infection bacteria and respiratory failure. In recent years, preventive and supportive probiotic therapies for respiratory tract infections (RTIs) have been increasingly strengthened, however, the use of oral administrative probiotics as functional foods is effective only for mild symptoms and not applicable for Acute RTIs (ARTIs). Here, we propose that direct spraying of probiotics into the nose can be a fast and effective symptomatic treatment for ARTIs.
Objectives: Investigate symptomatic treatment effects of probiotic product LiveSpo Navax, as liquid-suspension form containing Bacillus spores of safe B. subtilis ANA4 and B. clausii ANA39 strains, in children having acute respiratory diseases caused by RSV:
* Primary Objective: Evaluation of improved efficacy and reduced treatment time of LiveSpo Navax in children infected with RSV.
* Secondary Objectives: Measurement of changes in RSV viral load, co-infectious bacterial concentrations, and major cytokine indicators in the nasopharyngeal mucosa before and after 3 days using LiveSpo Navax.
Endpoints:
Primary endpoint: LiveSpo Navax alleviates RSV-infection symptoms about 25% more effectively, as indicated by 90% of patients using LiveSpo Navax (Navax group) are symptom-free at day 3-6 of intervention depending on symptoms, compared to 65% of patients in Control group.
Secondary endpoint: Patients in Navax group had more significant reductions in RSV load (\>10 fold) than patients in Control group at day 3 of intervention.
Study Population: Sample size is 100. Description of Sites: The study is carried out at Vietnam National Children's Hospital.
Description of Study Intervention: Totally 100 eligible patients are divided randomly into 2 groups (n = 50/group each): Patients in Control group received the routine treatment and three times per day 0.9% NaCl physiological saline while the and patients in Navax group received three times per day LiveSpo Navax in addition to the same standard of care treatment. The standard treatment regimen is 3-6 days but can be extended further depending on the severity of the patients' respiratory failure.
Study Duration: 12 months
Objectives: Investigate symptomatic treatment effects of probiotic product LiveSpo Navax, as liquid-suspension form containing Bacillus spores of safe B. subtilis ANA4 and B. clausii ANA39 strains, in children having acute respiratory diseases caused by RSV:
* Primary Objective: Evaluation of improved efficacy and reduced treatment time of LiveSpo Navax in children infected with RSV.
* Secondary Objectives: Measurement of changes in RSV viral load, co-infectious bacterial concentrations, and major cytokine indicators in the nasopharyngeal mucosa before and after 3 days using LiveSpo Navax.
Endpoints:
Primary endpoint: LiveSpo Navax alleviates RSV-infection symptoms about 25% more effectively, as indicated by 90% of patients using LiveSpo Navax (Navax group) are symptom-free at day 3-6 of intervention depending on symptoms, compared to 65% of patients in Control group.
Secondary endpoint: Patients in Navax group had more significant reductions in RSV load (\>10 fold) than patients in Control group at day 3 of intervention.
Study Population: Sample size is 100. Description of Sites: The study is carried out at Vietnam National Children's Hospital.
Description of Study Intervention: Totally 100 eligible patients are divided randomly into 2 groups (n = 50/group each): Patients in Control group received the routine treatment and three times per day 0.9% NaCl physiological saline while the and patients in Navax group received three times per day LiveSpo Navax in addition to the same standard of care treatment. The standard treatment regimen is 3-6 days but can be extended further depending on the severity of the patients' respiratory failure.
Study Duration: 12 months
Detailed Description
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Respiratory syncytial virus (RSV) is the most common virus that causes Acute Respiratory Tract Infections (ARTIs) in young children, with a high risk of serious bronchiolitis. RSV infection symptoms range from mild fever, cough, runny nose, and wheezing to severe symptoms such as difficulty breathing and respiratory failure. Cytokines in the airways of children with bronchiolitis, such as tumor necrosis factor (TNF-alpha), Interleukin-6 (IL-6) and IL-8, have been shown to increase at a very high level in primary RSV infection, and extreme elevation of IL-6 is associated with sudden death in children with RSV infection. The World Health Organization (WHO) estimates that 160,000-600,000 children under the age of five die or hospitalize each year as a result of RSV infection. There is currently no vaccine or specific treatment for RSV-infected children because monoclonal antibody palivizumab therapy and antiviral nucleotide drug ribavirin are either too expensive or too dangerous for children and are only recommended for high-risk patients.
In recent years, preventive and supportive therapies for respiratory tract infection have grown in popularity, with probiotics emerging as promising safe candidates for therapeutic support and antibiotic reduction. It is suggested that probiotics can capture viruses through direct interactions, or produce secondary growths that inhibit virus growth or stimulate the immune system to capture virus intrusion. However, the efficacy of oral digested probiotics on children's respiratory tracts has been slow to develop (normally it takes about 3-12 months) and is primarily used for prevention rather than supportive treatment of ARITs. As a result, alternative delivery routes for probiotics in the treatment of ARTIs are required.
The aim of the study about to evaluate the effectiveness of nasal-spraying probiotics containing two bacterial strains, Bacillus subtilis and Bacillus clausii in preventing and in supporting the treatment of children having acute respiratory symptoms due to RSV infection.
Methods: A randomized, blind, and controlled clinical trial are conducted. The patient's parents are required to provide the following information of their children: full name, sex, age, obstetric history, vaccination history, antibiotic use history… After informed consent, 100 patients with ARTIs due to RSV will be randomized into 2 groups (n = 50/group): the control group (named "Control" group) use 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 6 days, nasopharyngeal samples will be collected at day 0 and day 3 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 RSV 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 RSV-induced respiratory tract infections, including runny nose, chest depression, difficulty breathing, 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 in 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 RSV load and co-infection bacteria concentrations. △Ct for target genes is calculated as Ct (threshold cycle) at day 3 - 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 RSV-infection symptoms about 25% more effectively, as indicated by 90% of patients using LiveSpo Navax (Navax group) are symptom-free at day 3-6 of intervention depending on symptoms, compared to 65% of patients in Control group; (ii) Patients in Navax group has more significant reductions in RSV load (\>10 fold) than patients in Control group at day 3 of intervention.
In recent years, preventive and supportive therapies for respiratory tract infection have grown in popularity, with probiotics emerging as promising safe candidates for therapeutic support and antibiotic reduction. It is suggested that probiotics can capture viruses through direct interactions, or produce secondary growths that inhibit virus growth or stimulate the immune system to capture virus intrusion. However, the efficacy of oral digested probiotics on children's respiratory tracts has been slow to develop (normally it takes about 3-12 months) and is primarily used for prevention rather than supportive treatment of ARITs. As a result, alternative delivery routes for probiotics in the treatment of ARTIs are required.
The aim of the study about to evaluate the effectiveness of nasal-spraying probiotics containing two bacterial strains, Bacillus subtilis and Bacillus clausii in preventing and in supporting the treatment of children having acute respiratory symptoms due to RSV infection.
Methods: A randomized, blind, and controlled clinical trial are conducted. The patient's parents are required to provide the following information of their children: full name, sex, age, obstetric history, vaccination history, antibiotic use history… After informed consent, 100 patients with ARTIs due to RSV will be randomized into 2 groups (n = 50/group): the control group (named "Control" group) use 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 6 days, nasopharyngeal samples will be collected at day 0 and day 3 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 RSV 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 RSV-induced respiratory tract infections, including runny nose, chest depression, difficulty breathing, 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 in 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 RSV load and co-infection bacteria concentrations. △Ct for target genes is calculated as Ct (threshold cycle) at day 3 - 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 RSV-infection symptoms about 25% more effectively, as indicated by 90% of patients using LiveSpo Navax (Navax group) are symptom-free at day 3-6 of intervention depending on symptoms, compared to 65% of patients in Control group; (ii) Patients in Navax group has more significant reductions in RSV load (\>10 fold) than patients in Control group at day 3 of intervention.
Conditions
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Acute Respiratory Tract Infections
Keywords
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Respiratory Syncytial Virus (RSV)
Acute Respiratory Tract Infections (ARTIs)
Children
Nasal-spraying probiotics
Viral load
Co-infection bacteria
Cytokines
Bacillus spores
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Blind, randomized, and controlled clinical trial
Primary Study Purpose
TREATMENT
Blinding Strategy
TRIPLE
Participants
Caregivers
Investigators
LiveSpo Navax and placebo 0.9% NaCl physiological saline are indistinguishable regarding taste and smell. The color and turbidity of LiveSpo Navax suspension is unrecognizable to investigators except the PI and analyzer, nurses, patient's parents, and patients due to opaque plastic container.
Study Groups
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Control
Control group receives the routine treatment and uses 0.9% NaCl physiological saline:
Routine treatment is as follows:
* Oral administrative drugs: antipyretic paracetamol (Efferegant®️); anti-inflammatory corticosteroid methylprednisolon; antibiotics e.g. ampicillin and sulbactam complex (Ama-power®️), tobramycin (Medphatobra®️), or cefotaxim (Goldcefo®️), based on the results of antibiotic susceptibility test.
* Aerosol therapy: bronchodilator e.g. salbutamol (Ventolin ®️inhaler) or budesonide (Pulmicort ®️Respules).
Group Type
PLACEBO_COMPARATOR
0.9% NaCl physiological saline
Intervention Type
DRUG
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.
Navax
Navax group receives the routine treatment and uses NaCl 0.9% plus B. subtilis and B. clausii at 5 billions CFU/5 mL (LiveSpo®️ Navax):
Routine treatment is as follows:
* Oral administrative drugs: antipyretic paracetamol (Efferegant®️); anti-inflammatory corticosteroid methylprednisolon; antibiotics e.g. ampicillin and sulbactam complex (Ama-power®️), tobramycin (Medphatobra®️), or cefotaxim (Goldcefo®️), based on the results of antibiotic susceptibility test.
* Aerosol therapy: bronchodilator e.g. salbutamol (Ventolin ®️inhaler) or budesonide (Pulmicort ®️Respules).
Group Type
EXPERIMENTAL
LiveSpo Navax
Intervention Type
COMBINATION_PRODUCT
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.
Interventions
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LiveSpo Navax
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.
Intervention Type
COMBINATION_PRODUCT
0.9% NaCl physiological saline
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.
Intervention Type
DRUG
Other Intervention Names
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Registration number: No.210001337/PCBA-HN
Registration number: VD-32723-19
Eligibility Criteria
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Inclusion Criteria
* Children (male/female) aged from 4 to 60 months.
* Admitted hospital due to lower respiratory infection.
* RSV is positive by rapid test.
* Parents of the pediatric patient agree to participate in the study, explain and sign the research consent form.
* Admitted hospital due to lower respiratory infection.
* RSV is positive by rapid test.
* Parents of the pediatric patient agree to participate in the study, explain and sign the research consent form.
Exclusion Criteria
* Newborn babies.
* Have a history of drug allergy.
* Need oxygen therapy.
* Discharged before day 3.
* 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.
* Have a history of drug allergy.
* Need oxygen therapy.
* Discharged before day 3.
* 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.
Minimum Eligible Age
4 Months
Maximum Eligible Age
60 Months
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National Children's Hospital, Vietnam
OTHER
Sponsor Role
lead
Responsible Party
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Tran Thanh Tu
Vice Director of International Center, Vietnam National Children's Hospital
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Tu T Tran, PhD. MD.
Role: PRINCIPAL_INVESTIGATOR
International Center, Vietnam National Children's Hospital
Locations
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International Center, Vietnam National Children's Hospital
Hanoi, , Vietnam
Site Status
Countries
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Vietnam
References
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Related Links
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https://doi.org/10.4103/2455-3069.198381
Novel insight on probiotic Bacillus subtilis: mechanism of action and clinical applications.
Other Identifiers
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4711/QD-BVNTU
Identifier Type: OTHER
Identifier Source: secondary_id
2020S-06
Identifier Type: -
Identifier Source: org_study_id