Testing the Efficacy in Adults With Cold of HEalsea Rescue* (TEACHER)

Efficacy and Safety of Healsea® Hypertonic Nasal Spray 2.7% in the Treatment of Acute Infectious Rhinitis in Adults

Healsea® Rescue* is a CE-marked class I medical device. This is a saline-based nasal spray supplemented with a natural Symbiofilm™ extract (0.04%) isolated from the marine bacteria. Healsea® Rescue* is indicated in adults for the treatment of symptoms of acute respiratory tract infections, rhinitis or rhinosinusitis, and for reduction of the swelling of the nasal mucosa.

The goal of this clinical trial is to demonstrate that hypertonic saline solution and Symbiofilm™ act in a synergistic manner to alleviate symptoms of the acute rhinitis phase resulting in better efficacy than isotonic saline solution without Symbiofilm™ used as Placebo in adults with early symptoms of common cold / acute infectious rhinitis.

Study Overview

• Status: Completed
• Conditions: Common Cold
• Intervention / Treatment: Device: Healsea Rescue*; Device: Placebo

Detailed Description

Upper respiratory tract infections (URTIs) and sino-nasal symptoms are very frequent, especially during the fall and the winter. The common cold is caused by a variety of viruses such as human rhinoviruses and influenza viruses. The incidence of acute rhinitis/rhinosinusitis is very high, estimated to occur from 2 to 5 times per year in the average adult. However, the natural course of acute rhinitis in adults is favorable since 75% of persons have a reduction or resolution of symptoms within 7 days. Only 0.5 to 2.0% of subjects develop secondary bacterial sinusitis requiring antibiotic prescription. 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. The socioeconomic impact of acute rhinitis is well established: visits to GP, additional prescriptions and over prescription of antibiotics, workdays lost.

Although clinical evidence from well-designed trials is scarce, European and American guidelines for acute rhinosinusitis recommend daily nasal saline irrigation for reduction of the severity of symptoms and for speeding recovery. The exact mechanisms by which nasal irrigation works are not known. However, most of the experts agree that it is primarily a mechanical intervention leading to direct cleansing of the nasal mucosa. Hypertonic saline solutions are generally considered as more effective than isotonic saline solutions in reducing nasal symptoms in the acute phase. Nevertheless, the efficacy of such solution remains moderate.

Healsea® Rescue* is a CE-marked class I medical device. This is a saline-based nasal spray supplemented with a natural Symbiofilm™ extract (0.04%) isolated from the marine bacteria Bacillus licheniformis T14. The nasal solution is hypertonic (NaCl 2.7%). Symbiofilm™ is an exopolysaccharide with emulsifying properties and in vitro antibiofilm activity and detachment properties against various bacterial pathogens. Symbiofilm™ also protects in vitro human nasal epithelial cells viability after Rhinovirus, Adenovirus, Coronavirus OC43 and Flu infection.

The aim of this study is to demonstrate that hypertonic saline solution and Symbiofilm™ act in a synergistic manner to alleviate symptoms of the acute rhinitis phase resulting in better efficacy than isotonic saline solution without Symbiofilm™ used as Placebo.

The study comprises two parts:

- Part 1 (Day1-Day 8): treatment of the acute phase

• with Healsea® Rescue*, 2 puffs in each nostril 2 times per day during 7 days (14 intakes of the investigational device).

or • with isotonic nasal spray (Placebo), 2 puffs in each nostril 2 times per day during 7 days (14 intakes of the Placebo).

- Part 2 (Day 9-Day 13/15): follow-up phase.

The study comprises two visits and one telephone call:

• Visit 1 (V1) at Day 1
• Telephone call at Day 8
• End of study visit (Visit 2, V2) between Day 13 and Day 15.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1000
    • DCC Convex Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male/Female subjects >18 years
2. Acute infectious rhinitis/rhinosinusitis for ≤48h before trial entry
3. Symptoms of headache, muscle ache, chilliness, sore throat, blocked nose, runny nose, cough, sneezing with a score ≤9 (according to a self-rated symptom score; scale: 0 → 3 [0: no symptom to 3: severe intensity])
4. At least one of these symptoms: sore throat, runny nose or blocked nose (i.e., with a score ≥1)
5. Willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the information consent form
6. Patient with a smartphone and an internet connection.

Exclusion Criteria:

1. Known hypersensitivity/allergy to any component of the test device
2. Medical history or any current disease 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 or local corticosteroids (nasal route or inhalation) within 4 weeks before screening
7. Antihistamines intake for allergy when treatment was started from less than 4 weeks
8. Chronic decongestant use
9. 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)
10. Pregnant/Lactating female or absence of efficient contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healsea Rescue* group; Subjects will receive Healsea Rescue* according to its intended use.	Device: Healsea Rescue*; Subjects will be administered with Healsea Rescue* by spraying 2 puffs in each nostril 2 times per day during 7 days.
Placebo Comparator: Placebo group; Subjects will receive Placebo according to identical posology, instructions for use, contraindication, precaution of use and labelling to those of Healsea Rescue.	Device: Placebo; Subjects will be administered with isotonic saline nasal spray indistinguishable from the Healsea Rescue* by spraying 2 puffs in each nostril 2 times per day during 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (Area Under Curve) of Wisconsin Upper Respiratory Symptom Survey (WURSS-21) During First 8 Days of Symptoms as Compared Between Both Groups - Full Analysis Set (FAS)	The WURSS-21 questionnaire scores the severity and functional impact of a cold (items 2 to 11 and 12 to 20 respectively) plus 2 items for global severity and global change (items 1 and 21 respectively). Each item is scored from 0 (not sick / Do not have this symptom / Not at all / Very much better) to 7 (severely, severe, severely, very much worse) for global assessment, symptoms, functional impairment and global change respectively. The question 21 is not included in the calculation of the total score of the WURSS-21. The minimum WURSS-21 score is zero (0) and the maximum WURSS-21 score is one hundred forty (140). The questionnaire was completed in a diary once daily in the evening, taking into account the symptoms from the morning to the evening, during Day 2-Day 8 (day of the end of treatment). At Day 1, the WURSS-21 was completed during the visit. After Day 8, it was assessed once daily until the subject feels not sick for two consecutive days.	Treatment period, from Day 1 to Day 8
AUC (Area Under Curve) of Wisconsin Upper Respiratory Symptom Survey (WURSS-21) During First 8 Days of Symptoms as Compared Between Both Groups - Per Protocol Set (PP)	The WURSS-21 questionnaire scores the severity and functional impact of a cold (items 2 to 11 and 12 to 20 respectively) plus 2 items for global severity and global change (items 1 and 21 respectively). Each item is scored from 0 (not sick / Do not have this symptom / Not at all / Very much better) to 7 (severely, severe, severely, very much worse) for global assessment, symptoms, functional impairment and global change respectively. The question 21 is not included in the calulation of the total score of the WURSS-21. The minimum WURSS-21 score is zero (0) and the maximum WURSS-21 score is one hundred forty (140). The questionnaire was completed in a diary once daily in the evening, taking into account the symptoms from the morning to the evening, during Day 2-Day 8 (day of the end of treatment). At Day 1, the WURSS-21 was completed during the visit. After Day 8, it was assessed once daily until the subject feels not sick for two consecutive days.	Treatment period, from Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of the Symptoms Sub-score (Items 2-11) of the WURSS-21 During First 8 Days	The Symptoms' WURSS-21 questionnaire scores the severity of the cold (items 2 to 11). Each item is scored from 0 (Do not have this symptom) to 7 (Severe). The minimum Symptoms' WURSS-21 score is zero (0) and the maximum is seventy (70). The questionnaire was completed in a diary once daily in the evening, taking into account the symptoms from the morning to the evening, during Day 2-Day 8 (day of the end of treatment). At Day 1, the Symptoms' WURSS-21 was completed during the visit. After Day 8, it was assessed once daily until the subject feels not sick for two consecutive days.	Treatment period, from Day 1 to Day 8
AUC of the Quality of Life Sub-score (Items 12-20) of the WURSS-21 During First 8 Days	The Quality-of-Life' WURSS-21 questionnaire scores the impact of the cold on quality of life (items 12 to 20). Each item is scored from 0 (Not at all) to 7 (Severely). The minimum Quality-of-Life' WURSS-21 score is zero (0) and the maximum is sixty three (63). The questionnaire was completed in a diary once daily in the evening, taking into account the symptoms from the morning to the evening, during Day 2-Day 8 (day of the end of treatment). At Day 1, the Symptoms' WURSS-21 was completed during the visit. After Day 8, it was assessed once daily until the subject feels not sick for two consecutive days	Treatment period, from Day 1 to Day 8
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Runny Nose	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Plugged Nose	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Sneezing	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Sore Throat	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Cough	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Scratchy Throat	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Hoarseness	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Head Congestion	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Chest Congestion	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Duration of Cold Symptoms Assessed by Means of the WURSS-21: Duration of Feeling Tired	For each item, the duration is defined as the number of symptomatic days between Visit 1 and the first day the subject reports not to have this symptom for two consecutive days.	Through study completion, up to Day 15
Cumulative Number of Days of Usual Medication for Common Cold Use	Concomitant treatments (antipyretics, systemic or local mucolytics, decongestants, antitussives, antibiotics) use will be reported in the e-diary by the patient throughout the study, validated by the investigator at the end of study visit before being reported in the e-CRF.	Through study completion, up to Day 15
Subject Satisfaction Regarding Ease of Use of the Nasal Spray	At end of study visit (V2) subject satisfaction regarding ease of use will be recorded using a 4-points categorical scale (How would you characterize the use of Healsea® Rescue* nasal spray? 0: not easy ; 1: pretty easy ; 2: easy ; 3: very easy).	Between Day 13 and Day 15
Characterization of Residual Taste by the Subject	At end of study visit (V2) the residual taste after using the spray will be assessed by the subject using a 4-points categorical scale (How would you characterize the residual taste after spraying Healsea® Rescue*?0: not pleasant ; 1: neutral ; 2: pleasant ; 3: very pleasant).	Between Day 13 and Day 15
Characterization of Cleansing and Moistening of Nasal Mucosa With the Prescribed Treatment by the Subject	At end of study visit (V2) cleansing and moistening of nasal mucosa will be assessed by the subject using a 4-points categorical scale (How would you characterize the cleansing and moistening of nasal mucosa with Healsea® Rescue*?0: no improvement ; 1: slight improvement ; 2: moderate improvement; 3: very clear improvement).	Between Day 13 and Day 15

Collaborators and Investigators

• Sponsor: Lallemand Pharma AG
• Investigators: Principal Investigator: Emil KOLEV, MD, DCC Convex Ltd., Sofia, Bulgaria

Publications and helpful links

General Publications

• Barrett B, Brown RL, Mundt MP, Thomas GR, Barlow SK, Highstrom AD, Bahrainian M. Validation of a short form Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Health Qual Life Outcomes. 2009 Aug 12;7:76. doi: 10.1186/1477-7525-7-76.
• Rabago D, Zgierska A, Mundt M, Barrett B, Bobula J, Maberry R. Efficacy of daily hypertonic saline nasal irrigation among patients with sinusitis: a randomized controlled trial. J Fam Pract. 2002 Dec;51(12):1049-55.
• JACKSON GG, DOWLING HF, SPIESMAN IG, BOAND AV. Transmission of the common cold to volunteers under controlled conditions. I. The common cold as a clinical entity. AMA Arch Intern Med. 1958 Feb;101(2):267-78. doi: 10.1001/archinte.1958.00260140099015. No abstract available.
• 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.
• 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.
• Heikkinen T, Jarvinen A. The common cold. Lancet. 2003 Jan 4;361(9351):51-9. doi: 10.1016/S0140-6736(03)12162-9.
• Rosenfeld RM. CLINICAL PRACTICE. Acute Sinusitis in Adults. N Engl J Med. 2016 Sep 8;375(10):962-70. doi: 10.1056/NEJMcp1601749. No abstract available.
• King D, Mitchell B, Williams CP, Spurling GK. Saline nasal irrigation for acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015 Apr 20;2015(4):CD006821. doi: 10.1002/14651858.CD006821.pub3.
• Principi N, Esposito S. Nasal Irrigation: An Imprecisely Defined Medical Procedure. Int J Environ Res Public Health. 2017 May 11;14(5):516. doi: 10.3390/ijerph14050516.
• Talbot AR, Herr TM, Parsons DS. Mucociliary clearance and buffered hypertonic saline solution. Laryngoscope. 1997 Apr;107(4):500-3. doi: 10.1097/00005537-199704000-00013.
• Brown CL, Graham SM. Nasal irrigations: good or bad? Curr Opin Otolaryngol Head Neck Surg. 2004 Feb;12(1):9-13. doi: 10.1097/00020840-200402000-00004.
• van Haselen R, Thinesse-Mallwitz M, Maidannyk V, Buskin SL, Weber S, Keller T, Burkart J, Klement P. The Effectiveness and Safety of a Homeopathic Medicinal Product in Pediatric Upper Respiratory Tract Infections With Fever: A Randomized Controlled Trial. Glob Pediatr Health. 2016 Jul 4;3:2333794X16654851. doi: 10.1177/2333794X16654851. eCollection 2016.
• Brown RL, Obasi CN, Barrett B. Rasch Analysis of The WURSS-21 Dimensional Validation and Assessment of Invariance. J Lung Pulm Respir Res. 2016;3(2):00076. doi: 10.15406/jlprr.2015.03.00076. Epub 2016 Apr 11.
• 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): December 14, 2022
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: March 9, 2023
• First Submitted That Met QC Criteria: April 5, 2023
• First Posted (Actual): April 19, 2023

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: July 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Respiratory tract infection; Rhinosinusitis; Nasal irrigation; Acute infectious rhinitis
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Picornaviridae Infections; Common Cold
• Other Study ID Numbers: LPH-2201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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