LiveSpo Navax® Supports the Treatment of Acute Rhinosinusitis and Otitis Media

NCT05804123 | Completed DMC

• 2 other identifiers: TNLS.2021.03872/HĐĐĐ
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

Brief Summary

Acute respiratory tract infections (ARTIs), such as acute rhinosinusitis (ARS) and acute otitis media (AOM), are common worldwide and caused by viruses or bacteria entering the body through the mouth and nose. AOM frequently occurs in young children and is caused by bacterial reflux into the middle ear. ARS is a relatively common ARTIs and can occur at many ages. To accurately diagnose disease, careful clinical examination and accurate clinical judgment are required, as making a reasonable treatment regimen with the decision to use antibiotics. Probiotics have long been known to have beneficial effects on the digestive system. Not only limited to the gastrointestinal tract but probiotics are also known for their role in reducing infections in the respiratory system. Recently, the investigators have successfully conducted a clinical trial of nasal-spray Bacillus spore probiotics in children infected with respiratory syncytial virus (RSV), and the data show that the probiotics can rapidly and effectively relieve symptoms of RSV-induced ARTIs while exhibiting strong impacts in reducing viral load and inflammation. Here, the investigators conducted a study that directly spraying probiotics into the nose can effectively support to treatment of both ARS and AOM. The aim of the study about to evaluate the safety and effectiveness of nasal-spraying probiotics containing spores of Bacillus subtilis and Bacillus clausii in the supportive treatment of patients with ARS and AOM. Study Population: sample size is 120. Description of Sites: the study is carried out at Thai Binh Medical University Hospital and Thai Binh Children's Hospital. Description of Study Intervention: 120 eligible patients are divided into 2 groups (n=60/group) including the ARS group and the ARS accompanied by the AOM (ARS \& AOM) group. 60 patients in each of the above groups were randomly assigned to two subgroups (n=30/subgroup): Patients in the Control-ARS and Control-ARS \& AOM subgroups received the routine treatment and three times per day nasal-spraying 0.9% NaCl physiological saline. In contrast, the patients in the Navax-ARS and Navax-ARS \& AOM subgroups received three times per day nasal-spraying LiveSpo Navax® in addition to the same standard of care treatment. The standard treatment regimen is 3-7 days, depending on the severity of the disease when the patient arrives for the exam and the progression of the disease during the treatment period. Study duration: 18 months

Conditions

Upper Respiratory Tract Infections

Keywords

Acute rhinosinusitis (ARS); Acute otitis media (AOM); Nasal-spraying probiotics; Adult; Children; Infection bacteria; Cytokines; Immunoglobulin A; Bacillus spores

Outcome Measures

Primary Outcomes (2)

• Changes in percentages of patients with free acute rhinosinusitis symptoms

  Changes in percentage (%) of acute rhinosinusitis patients with free acute rhinosinusitis symptoms include nasal blockage/obstruction/congestion or runny nose, sneezing, headache, sinus pain (facial pain), loss of smell

  Day 3 compared to Day 0; Day 7 compared to Day 0

• Changes in percentages of patients with free acute otitis media symptoms

  Changes in percentages (%) of acute otitis media patients with free acute otitis media symptoms include fever, purulent discharge from the ear canal (ear discharge or otorrhea), earache (rubbing or pulling on the earlobe, tossing or turning, difficulty sleeping or crying), headache, and hearing loss temporary (poor response to sound), vomiting or diarrhea.

  Day 3 compared to Day 0

Secondary Outcomes (3)

• Changes in infection bacterial concentrations can cause acute rhinosinusitis (ARS) and acute otitis media (AOM)

  Day 3 compared to Day 0 and/or Day 7 compared to Day 0

• Changes in cytokines level

  Day 3 compared to Day 0 and/or Day 7 compared to Day 0

• Changes in immunoglobulin A level

  Day 3 compared to Day 0 and/or Day 7 compared to Day 0

Study Arms (4)

Control - Acute rhinosinusitis (ARS) subgroup

PLACEBO COMPARATOR

The Control - ARS subgroup receives the routine treatment and uses 0.9% NaCl physiological saline: Routine treatment (at the Thai Binh Medical University Hospital) is as follows: * Oral-administrative antibiotics: Augmentin (Amoxicillin and Acid Clavulanic). * Oral-administrative expectorant: Acetylcysteine * Nasal- spraying decongestant: Xylometazoline (Otrivin®)

Drug: 0.9% NaCl physiological saline Nasal-spraying; Drug: Augmentin 500Mg Tablet; Drug: Acetylcysteine; Drug: Xylometazoline Nasal

Navax - Acute rhinosinusitis (ARS) subgroup

EXPERIMENTAL

Navax - ARS subgroup receives the routine treatment and uses NaCl 0.9% plus B. subtilis and B. clausii at 5 billion Colony Forming Units (CFU)/5 mL (LiveSpo® Navax): Routine treatment (at the Thai Binh Medical University Hospital) is as follows: * Oral-administrative antibiotics: Augmentin (Amoxicillin and Acid Clavulanic). * Oral-administrative expectorant: Acetylcysteine * Nasal- spraying decongestant: Xylometazoline (Otrivin®)

Combination Product: LiveSpo Navax®; Drug: Augmentin 500Mg Tablet; Drug: Acetylcysteine; Drug: Xylometazoline Nasal

Control - ARS accompanied by the AOM (ARS & AOM) subgroup

PLACEBO COMPARATOR

The Control - ARS \& AOM subgroup receives the routine treatment and uses 0.9% NaCl physiological saline: Routine treatment (at the Thai Binh Children's Hospital) is as follows: * Oral-administrative antibiotics: Augmentin (Amoxicillin and Acid Clavulanic). Or injection or infusion-administrative antibiotics such as Imetoxim (Cefotaxime). * Antibiotic ear drops: Ciprofloxacin * Nasal- spraying decongestant: Xylometazoline (Otrivin®)

Drug: 0.9% NaCl physiological saline Nasal-spraying; Drug: Augmentin 500Mg Tablet; Drug: Xylometazoline Nasal; Drug: Cefotaxime; Drug: Ciprofloxacin

Navax - ARS accompanied by the AOM (ARS & AOM) subgroup

EXPERIMENTAL

Navax - ARS \& AOM subgroup 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 (at the Thai Binh Children's Hospital) is as follows: * Oral-administrative antibiotics: Augmentin (Amoxicillin and Acid Clavulanic). Or injection or infusion-administrative antibiotics such as Imetoxim (Cefotaxime). * Antibiotic ear drops: Ciprofloxacin * Nasal- spraying decongestant: Xylometazoline (Otrivin®)

Combination Product: LiveSpo Navax®; Drug: Augmentin 500Mg Tablet; Drug: Xylometazoline Nasal; Drug: Cefotaxime; Drug: Ciprofloxacin

Interventions

0.9% NaCl physiological saline Nasal-spraying DRUG

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.

Also known as: Registration number: VD-32723-19

Control - ARS accompanied by the AOM (ARS & AOM) subgroup; Control - Acute rhinosinusitis (ARS) subgroup

LiveSpo Navax® 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

Also known as: Registration number: No.210001337/PCBA-HN

Navax - ARS accompanied by the AOM (ARS & AOM) subgroup; Navax - Acute rhinosinusitis (ARS) subgroup

Augmentin 500Mg Tablet DRUG

Augmentin (GlaxoSmithKline Pte, product declaration No. VN-20169-16) is an oral antibiotic available in the form of 625 mg tablets, which are prescribed as routine treatment for children and adults, respectively.

Also known as: Registration number: VN-20169-16

Control - ARS accompanied by the AOM (ARS & AOM) subgroup; Control - Acute rhinosinusitis (ARS) subgroup; Navax - ARS accompanied by the AOM (ARS & AOM) subgroup; Navax - Acute rhinosinusitis (ARS) subgroup

Acetylcysteine DRUG

Acetylcysteine 200 mg (STADA Vietnam, product declaration No. VD-22667-15) is an oral expectorant, which is prescribed as routine treatment for children and adults, respectively.

Also known as: Registration number: VD-22667-15

Control - Acute rhinosinusitis (ARS) subgroup; Navax - Acute rhinosinusitis (ARS) subgroup

Xylometazoline Nasal DRUG

Otrivin (Xylometazoline 0.05%) (Novartis VietNam, product declaration No. VN-15558-12) is a nasal-spraying decongestant, which is prescribed as routine treatment for children and adults, respectively.

Also known as: Otrivin® 0.05 % with Registration number: VN-15558-12

Control - ARS accompanied by the AOM (ARS & AOM) subgroup; Control - Acute rhinosinusitis (ARS) subgroup; Navax - ARS accompanied by the AOM (ARS & AOM) subgroup; Navax - Acute rhinosinusitis (ARS) subgroup

Cefotaxime DRUG

Imetoxim 1g (Cefotaxime 1g) (Imexpharm Pharmaceutical, product declaration No. VD-26846-17) is an injection or infusion-administrative antibiotic, which is prescribed as routine treatment for children.

Also known as: Imetoxim 1g with Registration number: VD-26846-17

Control - ARS accompanied by the AOM (ARS & AOM) subgroup; Navax - ARS accompanied by the AOM (ARS & AOM) subgroup

Ciprofloxacin DRUG

Ciprofloxacin 0.3% (Vidipha Central Pharmaceutical, product declaration No. VD-15205-11) is an antibiotic ear drop, which is prescribed as routine treatment for children.

Also known as: Registration number: VD-15205-11

Control - ARS accompanied by the AOM (ARS & AOM) subgroup; Navax - ARS accompanied by the AOM (ARS & AOM) subgroup

Eligibility Criteria

• Age: 6 Months - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with acute rhinosinusitis: sudden onset of two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip); and/or facial pain/pressure; and/or reduction or loss of smell for \<12 weeks. In children: sudden onset of two or more of the symptoms: nasal blockage/obstruction/congestion or discolored nasal discharge, or cough (daytime and night-time) for \< 12 weeks
• Patients diagnosed with acute rhinosinusitis accompanied by acute otitis media: patients from 6 months to 7 years old, suffer from onset ear discharge not caused by otitis external, the tympanic membrane was ruptured with purulent.
• Patients are hospitalized or treated as outpatients but need periodic re-examination
• Have a complete medical record or medical examination book
• For patients under 18 years old, the patient's parents agreed to participate in the study that was explained and signed the study consent form.
• Patients \>18 years old: patients agreed to participate in the study, explained, and signed the study consent form.

You may not qualify if:

• The patient did not agree to participate in the study.
• There are not enough medical records or medical examination books.
• The patient moves out of the treatment unit (not for professional reasons).
• The outpatients but no periodic re-examination.
• Patients with congenital deafness, or deafness due to neurological causes: meningitis, obstetric complications, ear poisoning...
• Patients with congenital disease-causing disorders of maxillofacial development and mental and physical retardation.

Sponsors & Collaborators

• Anabio R&D: lead
• Thai Binh University of Medicine and Pharmacy: collaborator

Study Sites (1)

Thai Binh University of Medicine and Pharmacy, Thai Binh Medical University Hospital and Thai Binh Children's Hospital

Thái Bình, Vietnam

Location

Related Publications (11)

• Fekete S, Szabo D, Tamas L, Polony G. [The role of the microbiome in otorhinolaryngology]. Orv Hetil. 2019 Sep;160(39):1533-1541. doi: 10.1556/650.2019.31451. Hungarian.

  PMID: 31544493 BACKGROUND

• Yoon YK, Park CS, Kim JW, Hwang K, Lee SY, Kim TH, Park DY, Kim HJ, Kim DY, Lee HJ, Shin HY, You YK, Park DA, Kim SW. Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections. Infect Chemother. 2017 Dec;49(4):326-352. doi: 10.3947/ic.2017.49.4.326.

  PMID: 29299900 BACKGROUND

• Zernotti ME, Pawankar R, Ansotegui I, Badellino H, Croce JS, Hossny E, Ebisawa M, Rosario N, Sanchez Borges M, Zhang Y, Zhang L. Otitis media with effusion and atopy: is there a causal relationship? World Allergy Organ J. 2017 Nov 14;10(1):37. doi: 10.1186/s40413-017-0168-x. eCollection 2017.

  PMID: 29158869 BACKGROUND

• Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, Orlandi RR, Palmer JN, Patel ZM, Peters A, Walsh SA, Corrigan MD. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015 Apr;152(2 Suppl):S1-S39. doi: 10.1177/0194599815572097.

  PMID: 25832968 BACKGROUND

• Gwaltney JM Jr, Wiesinger BA, Patrie JT. Acute community-acquired bacterial sinusitis: the value of antimicrobial treatment and the natural history. Clin Infect Dis. 2004 Jan 15;38(2):227-33. doi: 10.1086/380641. Epub 2003 Dec 19.

  PMID: 14699455 BACKGROUND

• Song M, Hong HA, Huang JM, Colenutt C, Khang DD, Nguyen TV, Park SM, Shim BS, Song HH, Cheon IS, Jang JE, Choi JA, Choi YK, Stadler K, Cutting SM. Killed Bacillus subtilis spores as a mucosal adjuvant for an H5N1 vaccine. Vaccine. 2012 May 9;30(22):3266-77. doi: 10.1016/j.vaccine.2012.03.016. Epub 2012 Mar 22.

  PMID: 22446640 BACKGROUND

• Lefevre M, Racedo SM, Ripert G, Housez B, Cazaubiel M, Maudet C, Justen P, Marteau P, Urdaci MC. Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study. Immun Ageing. 2015 Dec 3;12:24. doi: 10.1186/s12979-015-0051-y. eCollection 2015.

  PMID: 26640504 BACKGROUND

• Cutting SM. Bacillus probiotics. Food Microbiol. 2011 Apr;28(2):214-20. doi: 10.1016/j.fm.2010.03.007. Epub 2010 Mar 24.

  PMID: 21315976 BACKGROUND

• Piewngam P, Zheng Y, Nguyen TH, Dickey SW, Joo HS, Villaruz AE, Glose KA, Fisher EL, Hunt RL, Li B, Chiou J, Pharkjaksu S, Khongthong S, Cheung GYC, Kiratisin P, Otto M. Pathogen elimination by probiotic Bacillus via signalling interference. Nature. 2018 Oct;562(7728):532-537. doi: 10.1038/s41586-018-0616-y. Epub 2018 Oct 10.

  PMID: 30305736 BACKGROUND

• Tran DM, Tran TT, Phung TTB, Bui HT, Nguyen PTT, Vu TT, Ngo NTP, Nguyen MT, Nguyen AH, Nguyen ATV. Nasal-spraying Bacillus spores as an effective symptomatic treatment for children with acute respiratory syncytial virus infection. Sci Rep. 2022 Jul 20;12(1):12402. doi: 10.1038/s41598-022-16136-z.

  PMID: 35858943 BACKGROUND

• Khieu TH, Le DP, Nguyen BT, Ngo BT, Chu HT, Truong DM, Nguyen HM, Nguyen AH, Pham TD, Van Nguyen AT. Alleviating symptoms of paediatric acute rhinosinusitis and acute otitis media with otorrhea using nasal-spraying Bacillus probiotics: a randomized controlled trial. Sci Rep. 2025 Jan 27;15(1):3410. doi: 10.1038/s41598-025-87372-2.

  PMID: 39870748 DERIVED

MeSH Terms

Conditions

Respiratory Tract Infections; Otitis Media

Interventions

Amoxicillin-Potassium Clavulanate Combination; Tablets; Acetylcysteine; xylometazoline; Cefotaxime; Ciprofloxacin

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases; Otitis; Ear Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Dosage Forms; Cysteine; Amino Acids, Sulfur; Amino Acids; Amino Acids, Peptides, and Proteins; Cephacetrile; Cephalosporins; Thiazines; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Officials

• Thanh Khieu Huu, MD.,PhD

  Thai Binh University of Medicine and Pharmacy

  PRINCIPAL INVESTIGATOR

• Binh Nguyen Thanh, Assoc. Prof.

  Thai Binh University of Medicine and Pharmacy

  PRINCIPAL INVESTIGATOR

• Anh Nguyen Thị Vân, Assoc. Prof.

  Anabio R&D Ltd

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Blind randomized controlled trial

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: April 7, 2023
• Study Start: October 28, 2021
• Primary Completion: April 5, 2024
• Study Completion: August 1, 2024
• Last Updated: August 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research and will be provided following review and approval of a study protocol, informed consent form (ICF), and clinical study report (CSR). For more information or to submit a request, please contact clinicaltrial.probiotics@gmail.com

Locations

VN (1)