Common Cold, Rhinitis Viral
Conditions
Keywords
nasal spray, supplemented isotonic saline solution, infectious rhinitis, children
Brief summary
The purpose of this post market clinical investigation is to demonstrate that Healsea® Babykids alleviates symptoms of the acute rhinitis phase with better efficacy than isotonic saline solution used as Placebo in children above 2 years.
Detailed description
Healsea® Babykids is an isotonic saline solution based nasal spray supplemented with a natural Symbiofilm® extract (0.04%) isolated from marine bacteria. Symbiofilm® has in vitro antibiofilm activity and protects in vitro human nasal epithelial cells viability after Rhinovirus, Adenovirus, coronavirus OC43 and flu infection. Healsea® Babykids is a nasal spray indicated in children above 2 years to clean and moisten the nose during colds 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. 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. 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 aim of this study is to demonstrate that Healsea® Babykids alleviates symptoms of the acute rhinitis phase with better efficacy than isotonic saline solution used as Placebo. The study comprises 2 parts: \- Part 1 (Day 1-Day 11): treatment of the acute phase • with Healsea® Babykids, 2 puffs in each nostril 2 times per day with a minimum of 7-day-treatment period (14 intakes of Healsea® Babykids) up to 10 days (20 intakes of the investigational device). or • with isotonic nasal spray (Placebo), 2 puffs in each nostril 2 times per day with a minimum of 7-day-treatment period (14 intakes of Placebo) up to 10 days (20 intakes of the investigational device). \- Part 2 (up to Day 15/Day 18): follow-up phase. The study comprises two visits: * Visit 1 (V1) at Day 1 * End of study visit (Visit 2, V2) between Day 15 and Day 18
Interventions
DEVICEHealsea Babykids
7-day-treatment period (14 intakes ) up to 10 days (20 intakes) .
DEVICEPlacebo
7-day-treatment period (14 intakes ) up to 10 days (20 intakes) .
Sponsors
Lallemand Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The investigational device and the comparator were indistinguishable. The comparator (isotonic nasal spray) used the same technology and the same packaging than Healsea Babykids. A white label with regulatory mentions for clinical investigations was stuck on the vial A white label with regulatory mentions was sticked on a white cardboard box used as secondary packaging. The IFUs (Bulgarian version) was included in the secondary packaging (on one face, Healsea Babykids, on the other face Placebo
Intervention model description
Randomized controlled trial double blind
Eligibility
Sex/Gender
ALL
Age
25 Months to 6 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Male/Female subjects \>2 and ≤6-year-old * 2\. Acute infectious rhinitis/rhinosinusitis for ≤48h before trial entry * 3\. Patient presenting with fever ≥ 37.5 °C at screening * 4\. Subjects with nasal congestion (blocked / stuffy nose) rated at least as moderate on the Acute Rhinitis Symptoms Severity Questionnaire, based on evaluation by the investigator * 5\. Subjects showing at least moderate grade for at least one of the following additional signs of acute rhinitis: runny nose, nasal crust (dry mucus), sneezing and cough * 6\. Written consent obtained from parent/legal guardians
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\. Chronic decongestant use * 8\. Recent (within the previous 2 days) intake of a common cold medicine that in the opinion of the investigator may influence ARSSQ score at screening (NSAID, nasal decongestants, cough medicines)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Area Under the Curve (AUC) of the Global Score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) During First 10 Days of Symptoms - Full Analysis Set (FAS) | From Day 1 to Day 10 | ARSSQ is a non-validated customized questionnaire. It includes 10 items assessing symptoms (questions 2 to 7), functional impairments (8 to 10), and global severity (question 1). Each item is scored from 0 (not present/no impact/ not sick) to 3 (severe, severe impact and very sick) for symptoms, functional impairment and global severity respectively. The questionnaire is to be completed in a diary once daily in the evening. The minimum ARSSQ score is zero (0) and the maximum ARSSQ score is thirty (30). |
| The Area Under the Curve (AUC) of the Global Score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) During First 10 Days of Symptoms - Per Protocol Set (PP) | From Day 1 to Day 10 | ARSSQ is a non-validated customized questionnaire. It includes 10 items assessing symptoms (questions 2 to 7), functional impairments (8 to 10), and global severity (question 1). Each item is scored from 0 (not present/no impact/ not sick) to 3 (severe, severe impact and very sick) for symptoms, functional impairment and global severity respectively. The questionnaire is to be completed in a diary once daily in the evening. The minimum ARSSQ score is zero (0) and the maximum ARSSQ score is thirty (30). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of Days of Concomitant Treatments Use That May Affect Common Cold Symptoms (Antibiotics, Antipyretics, Systemic or Local Mucolytics, Decongestants, Antitussives, Systemic and Topical Corticosteroids) | Through study completion, up to Day 18 | Concomitant treatments use (antibiotics, antipyretics, systemic or local mucolytics, decongestants, antitussives, systemic and topical corticosteroids) will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF. |
| Cumulative Number of Days of Antibiotics Intake | through study completion , up to day 18 | Antibiotics use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF. |
| Cumulative Number of Days of Antipyretics Intake | through study completion, up to day 18 | Antipyretics use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF. |
| Duration of Each Cold Symptom (Questions 2 to 7 of the ARSSQ) in Both Groups | Through study completion, up to Day 18 | For each separate symptom, the duration is defined as the number of days between Day 1 and the first day the parent/legal guardian reports the patient not having this symptom (Not present) for 2 consecutive days. Duration may be censored at Visit 2. |
| Cumulative Number of Days of Decongestants Use | through study completion, up to day 18 | Decongestants use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF. |
| Cumulative Number of Days of Antitussives Use | through study completion, up to day 18 | Antitussives use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF. |
| Cumulative Number of Days of Systemic and Topical Corticosteroids Use | Through study completion, up to day 18 | Systemic and topical corticosteroids use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF. |
| Cumulative Number of Days of Mucolytics Intake | Through study completion , up to day 18 | Mucolytics use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF. |
| Duration of Quality-of-life Impairment (Questions 8 to 10 of the ARSSQ). | Through study completion, up to Day 18 | For each separate symptom, the duration is defined as the number of days between Day 1 and the first day the parent/legal guardian reports the patient not having this symptom (Not present) for 2 consecutive days. Duration may be censored at Visit 2. |
Countries
Bulgaria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healsea Babykids Healsea® Babykids, nasal spray indistinguishable from the comparator. Subjects have to spray 2 puffs in each nostril 2 times per day with a minimum of 7-day-treatment period (14 intakes ) up to 10 days (20 intakes ).
Healsea Babykids: 7-day-treatment period (14 intakes ) up to 10 days (20 intakes) . | 100 |
| Placebo The comparator is a saline isotonic nasal spray considered as inert Placebo i.e., neutral for the nasal mucosa.
Subjects have to spray 2 puffs in each nostril 2 times per day with a minimum of 7-day-treatment period (14 intakes ) up to 10 days (20 intakes ).
Placebo: 7-day-treatment period (14 intakes ) up to 10 days (20 intakes) . | 100 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Healsea Babykids |
|---|---|---|---|
| Age, Continuous | 4.0 years STANDARD_DEVIATION 1.2 | 4.0 years STANDARD_DEVIATION 1.1 | 3.9 years STANDARD_DEVIATION 1.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 100 Participants | 200 Participants | 100 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 49 Participants | 97 Participants | 48 Participants |
| Sex: Female, Male Male | 51 Participants | 103 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 0 / 100 |
| other Total, other adverse events | 11 / 100 | 14 / 100 |
| serious Total, serious adverse events | 0 / 100 | 0 / 100 |
Outcome results
Primary
The Area Under the Curve (AUC) of the Global Score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) During First 10 Days of Symptoms - Full Analysis Set (FAS)
ARSSQ is a non-validated customized questionnaire. It includes 10 items assessing symptoms (questions 2 to 7), functional impairments (8 to 10), and global severity (question 1). Each item is scored from 0 (not present/no impact/ not sick) to 3 (severe, severe impact and very sick) for symptoms, functional impairment and global severity respectively. The questionnaire is to be completed in a diary once daily in the evening. The minimum ARSSQ score is zero (0) and the maximum ARSSQ score is thirty (30).
Time frame: From Day 1 to Day 10
Population: FAS: all the subjects from the Safety Population and with at least one post-baseline efficacy data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea Babykids | The Area Under the Curve (AUC) of the Global Score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) During First 10 Days of Symptoms - Full Analysis Set (FAS) | 78.1 score on a scale*day | Standard Deviation 28.9 |
| Placebo | The Area Under the Curve (AUC) of the Global Score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) During First 10 Days of Symptoms - Full Analysis Set (FAS) | 93.6 score on a scale*day | Standard Deviation 28.9 |
Comparison: Comparison of the means of AUC on global score or ARSSQ during the first 10 days of the study between both groups.p-value: 0.0013Wilcoxon (Mann-Whitney)
Primary
The Area Under the Curve (AUC) of the Global Score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) During First 10 Days of Symptoms - Per Protocol Set (PP)
ARSSQ is a non-validated customized questionnaire. It includes 10 items assessing symptoms (questions 2 to 7), functional impairments (8 to 10), and global severity (question 1). Each item is scored from 0 (not present/no impact/ not sick) to 3 (severe, severe impact and very sick) for symptoms, functional impairment and global severity respectively. The questionnaire is to be completed in a diary once daily in the evening. The minimum ARSSQ score is zero (0) and the maximum ARSSQ score is thirty (30).
Time frame: From Day 1 to Day 10
Population: PP: efficacy population based on the FAS for subjects without major protocol deviation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea Babykids | The Area Under the Curve (AUC) of the Global Score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) During First 10 Days of Symptoms - Per Protocol Set (PP) | 80.5 score on a scale*day | Standard Deviation 28.2 |
| Placebo | The Area Under the Curve (AUC) of the Global Score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) During First 10 Days of Symptoms - Per Protocol Set (PP) | 96 score on a scale*day | Standard Deviation 29.5 |
p-value: 0.0034t-test, 2 sided
Secondary
Cumulative Number of Days of Antibiotics Intake
Antibiotics use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF.
Time frame: through study completion , up to day 18
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healsea Babykids | Cumulative Number of Days of Antibiotics Intake | 108 number of days |
| Placebo | Cumulative Number of Days of Antibiotics Intake | 127 number of days |
p-value: >0.05Poisson regression
Secondary
Cumulative Number of Days of Antipyretics Intake
Antipyretics use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF.
Time frame: through study completion, up to day 18
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healsea Babykids | Cumulative Number of Days of Antipyretics Intake | 62 number of days |
| Placebo | Cumulative Number of Days of Antipyretics Intake | 86 number of days |
p-value: 0.0029Poisson regression
Secondary
Cumulative Number of Days of Antitussives Use
Antitussives use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF.
Time frame: through study completion, up to day 18
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healsea Babykids | Cumulative Number of Days of Antitussives Use | 23 number of days |
| Placebo | Cumulative Number of Days of Antitussives Use | 18 number of days |
p-value: 0.0789Poisson regression
Secondary
Cumulative Number of Days of Concomitant Treatments Use That May Affect Common Cold Symptoms (Antibiotics, Antipyretics, Systemic or Local Mucolytics, Decongestants, Antitussives, Systemic and Topical Corticosteroids)
Concomitant treatments use (antibiotics, antipyretics, systemic or local mucolytics, decongestants, antitussives, systemic and topical corticosteroids) will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF.
Time frame: Through study completion, up to Day 18
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healsea Babykids | Cumulative Number of Days of Concomitant Treatments Use That May Affect Common Cold Symptoms (Antibiotics, Antipyretics, Systemic or Local Mucolytics, Decongestants, Antitussives, Systemic and Topical Corticosteroids) | 317 number of days |
| Placebo | Cumulative Number of Days of Concomitant Treatments Use That May Affect Common Cold Symptoms (Antibiotics, Antipyretics, Systemic or Local Mucolytics, Decongestants, Antitussives, Systemic and Topical Corticosteroids) | 389 number of days |
p-value: 0.0015Poisson regression
Secondary
Cumulative Number of Days of Decongestants Use
Decongestants use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF.
Time frame: through study completion, up to day 18
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healsea Babykids | Cumulative Number of Days of Decongestants Use | 149 number of days |
| Placebo | Cumulative Number of Days of Decongestants Use | 220 number of days |
p-value: 0.0513Poisson regression
Secondary
Cumulative Number of Days of Mucolytics Intake
Mucolytics use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF.
Time frame: Through study completion , up to day 18
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healsea Babykids | Cumulative Number of Days of Mucolytics Intake | 44 number of days |
| Placebo | Cumulative Number of Days of Mucolytics Intake | 85 number of days |
p-value: 0.0006Poisson regression
Secondary
Cumulative Number of Days of Systemic and Topical Corticosteroids Use
Systemic and topical corticosteroids use will be reported in the paper diary by parents/legal guardians throughout the study, validated by the investigator at the end of the study visit before being reported in the e-CRF.
Time frame: Through study completion, up to day 18
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healsea Babykids | Cumulative Number of Days of Systemic and Topical Corticosteroids Use | 25 number of days |
| Placebo | Cumulative Number of Days of Systemic and Topical Corticosteroids Use | 66 number of days |
p-value: <0.0001Poisson regression
Secondary
Duration of Each Cold Symptom (Questions 2 to 7 of the ARSSQ) in Both Groups
For each separate symptom, the duration is defined as the number of days between Day 1 and the first day the parent/legal guardian reports the patient not having this symptom (Not present) for 2 consecutive days. Duration may be censored at Visit 2.
Time frame: Through study completion, up to Day 18
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea Babykids | Duration of Each Cold Symptom (Questions 2 to 7 of the ARSSQ) in Both Groups | 6.92 Number of days | Standard Deviation 2.14 |
| Placebo | Duration of Each Cold Symptom (Questions 2 to 7 of the ARSSQ) in Both Groups | 7.61 Number of days | Standard Deviation 2.05 |
Comparison: Comparison of the mean duration of common cold during the study between both groups.p-value: 0.0209Cox survival regression and p Wald
Secondary
Duration of Quality-of-life Impairment (Questions 8 to 10 of the ARSSQ).
For each separate symptom, the duration is defined as the number of days between Day 1 and the first day the parent/legal guardian reports the patient not having this symptom (Not present) for 2 consecutive days. Duration may be censored at Visit 2.
Time frame: Through study completion, up to Day 18
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healsea Babykids | Duration of Quality-of-life Impairment (Questions 8 to 10 of the ARSSQ). | 6.46 Duration in Days | Standard Deviation 1.92 |
| Placebo | Duration of Quality-of-life Impairment (Questions 8 to 10 of the ARSSQ). | 7.03 Duration in Days | Standard Deviation 1.97 |
Comparison: Comparison of the mean duration of impact of common cold on quality of life during the study between both groups.p-value: 0.0399Cox survival regression and p Wald