Symbiofilm Trial in Allergic Kids (SYMBIOFILM-TAK)

Impact of Adding Healsea® Isotonic Nasal Spray to Conventional Therapies for the Care of Children With Allergic Rhinitis Presenting With Symptoms of Acute Infectious Rhinitis: an Observational Study

Healsea® Children is a seawater-based nasal spray supplemented with a natural Symbiofilm® extract (0.02%) isolated from marine bacteria. Symbiofilm has antibiofilm activity against various bacterial pathogens involved in respiratory tract infections.Healsea® Children is indicated in the cleaning and moistening of nasal mucosa during common cold and rhinitis for children above 6 years.

This non interventional post-market clinical investigation aimed to confirm the benefit of Healsea® Children in real life setting in children with perennial allergy who are more prone to common cold.

Study Overview

• Status: Completed
• Conditions: Allergy; Common Cold
• Intervention / Treatment: Device: Healsea® Children; Other: Conventional therapies for common cold

Detailed Description

Healsea® Children is a seawater-based nasal spray supplemented with a natural Symbiofilm® extract (0.02%) isolated from marine bacteria. Symbiofilm® is an exopolymeric composition with emulsifying properties, in vitro antibiofilm activity and detachment properties against various bacterial pathogens involved in respiratory tract infections. Symbiofilm® has no bacteriostatic nor bactericidal activities. Healsea® Children is indicated in the cleaning and moistening of nasal mucosa during common cold and rhinitis.

The common cold is an acute viral infection of the upper respiratory tract, involving, to variable degrees, sneezing, nasal congestion and discharge (rhinorrhea), sore throat, cough, low-grade fever, headache, and malaise (1). It can be caused by members of several families of viruses; the most common are rhinoviruses. Acute viral rhinitis is generally self-limiting. In children where the illness is not self-limiting and extends beyond 7-10 days, many agree that a bacterial infection is likely (1). Bacterial over infections and progression to a chronic state are favoured by the formation of biofilms, which facilitate bacterial growth and persistence as well as reducing antibiotic efficacy (2-3).

Allergic diseases may play a particular role in promoting the respiratory infection recurrences (4). The physiological immune response is impaired in allergic subjects and allergic inflammation favours predisposition to respiratory infections. Subjects with allergic disorders may have functional defect of type 1 immune response that is relevant in fighting infections (5-6).

Allergic rhinitis (AR) may affect up to 40% of the paediatric population. Nasal symptoms are caused by exposure to an allergen to which a patient is sensitized.

AR is characterized by typical nasal symptoms and immunoglobulin E (IgE) -mediated inflammation. The allergic inflammatory process releases many cytokines and other proinflammatory proteins. Inflammation caused by nasal allergy leads to obstruction, fluid accumulation and acute disease. If these diseases are unsuccessfully treated, a chronic state of inflammation, obstruction, and infection develops that can cause mucosal damage and, ultimately, chronic disease (7).

For these reasons, the paediatric IgE-dependent allergic population that is more prone to common cold represents a suitable target for Healsea® Children (8-9).

During this prospective post-market clinical investigation, IgE-dependent allergic children with early symptoms of infectious rhinitis will be followed, children being treated with Healsea® Children on top of common cold conventional therapies or with conventional therapies only (excluded nasal irrigation).

Conventional therapies for non-complicated infectious rhinitis are symptomatic but are not without side effects. For example, decongestant use can increase blood pressure, antihistamine intake is associated with drowsiness.

Healsea® Children represents an interesting alternative that can not only improve acute infectious rhinitis symptomatology but could also limit the complication and progression to chronic state.

This non interventional post-market clinical investigation aimed to confirm the benefit of Healsea® Children in a real life setting in children with perennial allergy.

• Study Type: Observational
• Enrollment (Actual): 186

Contacts and Locations

Study Locations

• Poland
  • Białystok, Poland, 15-430
    • Research Site
  • Białystok, Poland, 15-010
    • Research Site
  • Bydgoszcz, Poland, 85-048
    • Research Site
  • Dys, Poland, 21-003
    • Research Site
  • Głowno, Poland, 95-015
    • Research Site
  • Kraków, Poland, 30-644
    • Research Site
  • Lublin, Poland, 20-093
    • Research Site
  • Lublin, Poland, 20-552
    • Research Site
  • Lublin, Poland, 20-141
    • Research Site
  • Lublin, Poland, 20-803
    • Research Site
  • Lublin, Poland, 20-865
    • Research Site
  • Rzeszów, Poland, 35-061
    • Research Site
  • Tarnów, Poland, 33-100
    • Research Site
  • Warszawa, Poland, 04-314
    • Research Site
  • Łomża, Poland, 18-402
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 10 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population comprises children 6 to10 years old with perennial allergy and early symptoms of common cold.

The recruitment will be competitive in both group, exposed to Healsea® Children or not exposed to Healsea® Children. However, when 100 patients will be recruited in one group, the recruitment will be stopped in this group but will continue in the other group until 100 patients to be enrolled.

Description

Inclusion Criteria:

1. Male/Female subjects ≥6 and ≤10-year-old
2. AsIgE (Allergy specific IgE) ≥ class 2 (RAST) or positive prick test for at least one perennial allergen
3. Acute infectious rhinitis/rhinosinusitis for ≤48h before trial entry
4. Patient presenting with fever ≥ 37.5 °C at screening
5. Symptoms of headache, muscle ache, chilliness, sore throat, blocked nose, runny nose, cough, sneezing with a total score ≤9 (according to a physician-rated symptom score; scale: 0 to 3 [0: no symptom to 3: severe intensity])
6. At least one of these symptoms: sore throat, runny nose or blocked nose (i.e., with a score ≥1)
7. Written consent obtained from parent/legal guardians
8. Written assent obtained from patient

Exclusion Criteria:

1. Known hypersensitivity/allergy to any component of the test device
2. Medical history that is considered by the investigator as a reason for non-inclusion,
3. Severe nasal septum deviation or other condition that could cause nasal obstruction such as the presence of nasal polyps
4. History of nasal or sinus surgery that in the opinion of the investigator may influence symptom scores
5. Antibiotic intake within 2 weeks before screening
6. Systemic corticosteroids within 4 weeks before screening
7. Antihistamines intake for allergy when treatment was started from less than 4 weeks
8. Bacterial lysate intake within 6 months before screening
9. Chronic decongestant use
10. Recent (within the previous 2 days) intake of a common cold medicine that in the opinion of the investigator may influence symptom score at screening (NSAID, nasal decongestants, cough medicines)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healsea® Children: isotonic seawater based nasal spray supplemented with natural Symbiofilm® extract; Children will receive Healsea® Children nasal spray on top of conventional therapies for common cold, as needed.	Device: Healsea® Children; Children will be administered Healsea Children , one puff (1-2 sec) in each nostril twice a day for 10 days on top of conventional therapies, as needed; Other Names: Conventional therapies for common cold; Other: Conventional therapies for common cold; Children will receive conventional therapies for common cold, nasal irrigation excluded (antipyretics, mucolytics, decongestants, antitussives, systemic and topical corticosteroids, antibiotics)
Conventional therapies; Children will receive conventional therapies for common cold as needed, nasal irrigation excluded	Other: Conventional therapies for common cold; Children will receive conventional therapies for common cold, nasal irrigation excluded (antipyretics, mucolytics, decongestants, antitussives, systemic and topical corticosteroids, antibiotics)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (Area Under Curve) of the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS-K) During the 10-day Treatment Period	The WURSS-K will be assessed once daily, from Day1 to Day10 (treatment period) WURSS-K is a 3-dimensional structure questionnaire specifically designed for children 4 to 10 years of age. It includes 6 items assessing symptoms (symptoms score: runny nose, stuffy nose, sneezing, sore throat, cough, feeling tired), 7 items assessing functional impairments (quality of life score: think, sleep, breathe, talk, walk/climb stairs/exercise, go to school, play with friends), 1 item assessing global severity. All these items are scored from 0 (absent or no impairment) through 1 (a little bad), 2 (bad) and 3 (very bad). The AUC value of the WURSS-K during the 10 day- treatment period is comprised between 0 WURSS-K score*day (no impairement) and 420 WURSS-K score *day (maximal impairement)	Cumulative AUC of the WURSS score assessed from Day 1 to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Days With Runny Nose	During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Runny nose is the item 2	Number of days with runny nose during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Number of Days With Stuffy Nose	During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Stuffy nose is the item 3.	Number of days with stuffy nose during the 10-day treatment period and a follow-up period of 20 days, up to 30 days
Number of Days With Sneezing	During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of common cold symptoms in both groups. Sneezing is the item 4.	Number of days with sneezing during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Number of Days With Sore Throat	During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Sore throat is the item 5.	Number of days with sore throat during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Number of Days With Cough	During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Cough is the item 6.	Number of days with cough during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Number of Days With "Feeling Tired"	During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of each common cold symptoms in both groups. Feeling tired is the item 7.	Number of days with "feeling tired" during the 10-day treatment period and a follow-up of 20 days, up to 30 days
Respiratory Complication Requiring Antibiotic Prescription After the10-day Treatment Period	The number of subjects who develop respiratory complication requiring antibiotic prescription during a 20-day follow-up period after the treatment period will be assessed in both groups and compared	Number of subjects with respiratory complications during the 20-day follow-up period
Number of Participants With Use of Concomitant Treatments	Number of subjects who took at least one concomitant treatment (antibiotics, antipyretics, systemic or local mucolytics, decongestants, antitussives, systemic and topical corticosteroids) that may impact symptoms of common cold and comparaison between groups	During 10-day treatment period and a follow-up period of 20 days, up to 30 days

Collaborators and Investigators

• Sponsor: Lallemand Pharma AG
• Investigators: Principal Investigator: Andrzej EMERYK, MD, PhD, University Children Hospital, Lublin, Poland

Publications and helpful links

General Publications

• Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Meco C, Matricardi PM, O'Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia P, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kawauchi H, Kjeldsen A, Klimek L, Krzeski A, Kopacheva Barsova G, Kim SW, Lal D, Letort JJ, Lopatin A, Mahdjoubi A, Mesbahi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Otori N, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Riechelmann H, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Sindvongs K, Soklic Kosak T, Stjarne P, Sutikno B, Steinsvag S, Tantilipikorn P, Thanaviratananich S, Tran T, Urbancic J, Valiulius A, Vasquez de Aparicio C, Vicheva D, Virkkula PM, Vicente G, Voegels R, Wagenmann MM, Wardani RS, Welge-Lussen A, Witterick I, Wright E, Zabolotniy D, Zsolt B, Zwetsloot CP. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600.
• Yan J, Bassler BL. Surviving as a Community: Antibiotic Tolerance and Persistence in Bacterial Biofilms. Cell Host Microbe. 2019 Jul 10;26(1):15-21. doi: 10.1016/j.chom.2019.06.002.
• Varricchio A, La Mantia I, Brunese FP, Ciprandi G. Inflammation, infection, and allergy of upper airways: new insights from national and real-world studies. Ital J Pediatr. 2020 Feb 10;46(1):18. doi: 10.1186/s13052-020-0782-z.
• Ciprandi G, Tosca MA, Fasce L. Allergic children have more numerous and severe respiratory infections than non-allergic children. Pediatr Allergy Immunol. 2006 Aug;17(5):389-91. doi: 10.1111/j.1399-3038.2006.00413.x.
• Cirillo I, Marseglia G, Klersy C, Ciprandi G. Allergic patients have more numerous and prolonged respiratory infections than nonallergic subjects. Allergy. 2007 Sep;62(9):1087-90. doi: 10.1111/j.1398-9995.2007.01401.x. Epub 2007 Jun 18.
• Eifan AO, Durham SR. Pathogenesis of rhinitis. Clin Exp Allergy. 2016 Sep;46(9):1139-51. doi: 10.1111/cea.12780.
• De Corso E, Lucidi D, Cantone E, Ottaviano G, Di Cesare T, Seccia V, Paludetti G, Galli J. Clinical Evidence and Biomarkers Linking Allergy and Acute or Chronic Rhinosinusitis in Children: a Systematic Review. Curr Allergy Asthma Rep. 2020 Sep 5;20(11):68. doi: 10.1007/s11882-020-00967-9.
• Lin SW, Wang SK, Lu MC, Wang CL, Koo M. Acute rhinosinusitis among pediatric patients with allergic rhinitis: A nationwide, population-based cohort study. PLoS One. 2019 Feb 12;14(2):e0211547. doi: 10.1371/journal.pone.0211547. eCollection 2019.
• Rabin N, Zheng Y, Opoku-Temeng C, Du Y, Bonsu E, Sintim HO. Biofilm formation mechanisms and targets for developing antibiofilm agents. Future Med Chem. 2015;7(4):493-512. doi: 10.4155/fmc.15.6. Erratum In: Future Med Chem. 2015;7(10):1362. doi: 10.4155/fmc.15.77.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): November 3, 2022
• Study Completion (Actual): November 3, 2022

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Infectious rhinitis, nasal irrigation, perennial allergy
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Picornaviridae Infections; Common Cold
• Other Study ID Numbers: LPH-2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No