Cough, Upper Respiratory Tract Infection
Conditions
Keywords
cough, common cold, antitussive agents, mucosal protection, medical device
Brief summary
The purpose of this study is to determine if there is comparable efficacy between carbocisteine and a protective cough syrup from natural ingredients in children's cough due to upper respiratory tract infections (URTI) such as the common cold. The hypothesis is that protecting the throat is very useful in decreasing cough severity, both day and night, without needing to subdue such an important reflex as cough, and without only acting on mucous fluidification, especially in children where sedation and excessive fluidification is dangerous. The research hypothesis is that the protective (Grintuss) Syrup relieves cough (frequency, intensity, degree of disturbance due to nocturnal cough, and improves the quality of sleep of the child) as much as or more than the carbocysteine syrup usually used to treat children (Syr Mucolit).
Detailed description
Cough is a life saving reflex, therefore it is important, especially in pediatrics, to calm cough spells without sedating the reflex. Mucolytic agents have been shown to be helpful but side effects have been reported and use has been prohibited under 2 years of age. Therefore, a completely safe and effective cough remedy has not been officially reported yet in a randomised trial. Looking into other mechanisms for cough management such as protection of irritated pharynx mucosa from post nasal drip or other irritating substances is theoretically sound and shows practical interesting results. A parallel comparison of efficacy and tolerability between such protective mechanism (acting through a barrier and radical scavenging action) due to natural substances (honey, plantago lanceolata, grindelia robusta and helichrysum italicum) and a mucolytic substance has not been done so far, in young children, especially in a time frame of 4 days. The intent of this study is to use the protective syrup versus carbocysteine in children with moderate to severe night and daily cough, measured with a validated parent questionnaire. The invasiveness of cough is followed immediately after one night administration of the study products and daily for four days. A similar effectiveness of the protective cough syrup as compared to carbocisteine is considered very interesting due to the mechanism of the remedy.
Interventions
DEVICEprotective cough syrup
The mucoadhesive and radical scavenging properties of the components create a protective film on the pharynx which protects irritated mucosa from cough generating stimuli such as post nasal drip, irritating elements, dehydration.
DRUGcarbocisteine cough syrup
Mucolytic
Sponsors
Aboca Spa Societa' Agricola
Clalit Health Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
* cough attributed to URTI such as the common cold * 2-5 years of age * moderate to severe day cough according to questionnaire (score at least 3 on all 3 questions relating to day cough) considering the day prior to enrollment. * moderate to severe night cough score according to questionnaire (score at least 3 of 2 of the three questions relating to the evaluation of nocturnal cough (frequency of nocturnal cough, impact of the sleep of the child and impact on the sleep of the parent) * signature of informed consent
Exclusion criteria
* Children with the diagnosis of diseases of the lower respiratory tract: inflammation of the larynx, trachea, bronchi, pneumonia, asthma, sinusitis, allergic rhinitis, as well as heart disease. * Children who received cough medicines or drugs containing antihistamines the day prior to study entry. * Known hypersensitivity to honey or any other component of the experimental product such as Grindelia, Helichrysum, essential oils natural flavourings of Lemon, Sweet Orange, Myrtle; Lemon natural flavouring * Children who received any steroid preparation (spray nozzle , or syrup , or other similar the day before study entry ) * Known sensitivity to carbocysteine specifically to the comparator Mucolit * gastric ulcer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Night Cough Score on First Night of Treatment (From N0 to N1) | 1 night from before enrollment (N0) to first night after treatment (N1) | Night cough is most bothersome to the child and family. Cough was measured with a validated questionnaire which asks parents to rate 5 aspects of night cough: frequency, severity, bothersomeness, child sleep and parent sleep according to a 7 point Likert scale, from 0 (not at all) to 6 (extremely). Lower scores indicate a better condition. The morning after the first night of treatment (N1) the parents rated the passed night by scoring from 0-6 each of the 5 aspects of night cough. The sum of scores for all 5 aspects gives the combined night cough score. This score, ranging between 0-30, was subtracted from the sum of all aspects, also ranging between 0-30, form the basal night cough score of the night before enrollment (N0). This change is recorded as change in combined night cough score and it refers to the change from N0 to N1. Negative values of the change indicate an improvement in the condition of the patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Night Cough Score at End of Study (From N0 to N4) | 4 nights (onset of trial Night 1 to Night 4) and 3 days | A validated cough questionnaire measuring 5 aspects of night cough (frequency, severity, bothersomeness, child sleep and parents' sleep) on a 7 point Likert scale was used each morning to rate the passed night. The scale rates each parameter from 0 (not at all) to 6 (extremely). Every night of the trial is rated. The morning after the last night of the study (N4) the parents rated the passed night by scoring from 0-6 each of the 5 aspects of night cough. The summed score for all aspects gives the combined night cough score. This score, ranging between 0-30, was subtracted from the sum of all aspects, also ranging between 0-30, form the basal night cough score of the night before enrollment (N0). This change is recorded as change in combined night cough score and it refers to the change from N0 to N4. Negative values of the change indicate an improvement in the condition of the patient. |
| Change in Day Cough Score at End of Study (From D0 to D4) | 4 nights (onset of trial Night 1 to Night 4) and 3 days | A validated cough questionnaire measuring 3 aspects of daytime cough (frequency, severity, bothersomeness) on a 7 point Likert scale was used each evening to rate the passed day, as regards these aspects. The scale rates each parameter from 0 (not at all) to 6 (extremely). Every day of the trial is rated. The last evening of the study (D4) the parents rated the passed day by scoring from 0-6 each of the 3 aspects of day cough. The summed score for all aspects gives the combined day cough score. This score, ranging between 0-18, was subtracted from the sum of all aspects, also ranging between 0-18, form the basal day cough score of the day before enrollment (D0). This change is recorded as change in combined day cough score and it refers to the change from D0 to D4. Negative values of the change indicate an improvement in the condition of the patient. |
Countries
Israel
Participant flow
Recruitment details
Recruiting took place within the Clalit health service community day hospitals. Community day hospitals are places where parents go for usual illnesses and treat most community ailments.
Pre-assignment details
Access for eligibility= 195 Excluded =45 (refused to participate n= 24, not meeting inclusion criteria n=21)
Participants by arm
| Arm | Count |
|---|---|
| Protective Cough Syrup syrup containing honey, plantago lanceolata, grindelia robusta, helichrysum italicum in a syrup form. The cough syrup is a CE marked medical device acting in a non pharmacological way to reduce cough.
Dosage: 6.5 ml three times a day for the duration of the study (4 nights, 3 days)
protective cough syrup: The mucoadhesive and radical scavenging properties of the components create a protective film on the pharynx which protects irritated mucosa from cough generating stimuli such as post nasal drip, irritating elements, dehydration.
Enrolled: 150 completed pre-treatment questionnaire and randomized into groups Allocated protective syrup n = 78 received intervention n= 78 Lost to follow up n=3 Discontinued intervention n=0 Analyzed n=75 Excluded from analysis n=0 | 78 |
| Carbocisteine Cough Syrup Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)
carbocisteine cough syrup: Mucolytic
Enrolled: 150 completed pre-treatment questionnaire and randomized into groups Allocated carbocisteine syrup n = 72 received intervention n= 72 Lost to follow up n=6 Discontinued intervention n=0 Analyzed n=66 Excluded from analysis n=0 | 72 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 6 |
Baseline characteristics
| Characteristic | Protective Cough Syrup | Carbocisteine Cough Syrup | Total |
|---|---|---|---|
| Age, Continuous | 42.49 months STANDARD_DEVIATION 12.96 | 43.17 months STANDARD_DEVIATION 14.57 | 42.8 months STANDARD_DEVIATION 13.7 |
| Participants coughing since ≥ 3 days at time of enrollment | 47 participants | 46 participants | 93 participants |
| Region of Enrollment Israel | 78 participants | 72 participants | 150 participants |
| Sex: Female, Male Female | 41 Participants | 38 Participants | 79 Participants |
| Sex: Female, Male Male | 37 Participants | 34 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 75 | 9 / 66 |
| serious Total, serious adverse events | 0 / 75 | 0 / 66 |
Outcome results
Primary
Change in Night Cough Score on First Night of Treatment (From N0 to N1)
Night cough is most bothersome to the child and family. Cough was measured with a validated questionnaire which asks parents to rate 5 aspects of night cough: frequency, severity, bothersomeness, child sleep and parent sleep according to a 7 point Likert scale, from 0 (not at all) to 6 (extremely). Lower scores indicate a better condition. The morning after the first night of treatment (N1) the parents rated the passed night by scoring from 0-6 each of the 5 aspects of night cough. The sum of scores for all 5 aspects gives the combined night cough score. This score, ranging between 0-30, was subtracted from the sum of all aspects, also ranging between 0-30, form the basal night cough score of the night before enrollment (N0). This change is recorded as change in combined night cough score and it refers to the change from N0 to N1. Negative values of the change indicate an improvement in the condition of the patient.
Time frame: 1 night from before enrollment (N0) to first night after treatment (N1)
Population: the population analyzed are the children who completed the protocol and submitted the complete questionnaire for night and day cough. 78 patients were enrolled in the protective syrup Group and 72 in the carbocysteine Group. 3 patients in the protective syrup group and 6 in the carbocysteine group never began the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Protective Cough Syrup | Change in Night Cough Score on First Night of Treatment (From N0 to N1) | -5.16 change in combined night cough score | Standard Error 0.85 |
| Carbocisteine Cough Syrup | Change in Night Cough Score on First Night of Treatment (From N0 to N1) | -1.77 change in combined night cough score | Standard Error 0.67 |
Comparison: The sample size was calculated to detect a 0.75 point difference between any two treatment groups with a 90% power and p\<0.05. Such sample size was 60 subject which was elevated ot 75 subjects per group to account for drop outs. For comparison of cough evaluation before and after treatment a paired Student t test was used.p-value: <0.01t-test, 2 sided
Secondary
Change in Day Cough Score at End of Study (From D0 to D4)
A validated cough questionnaire measuring 3 aspects of daytime cough (frequency, severity, bothersomeness) on a 7 point Likert scale was used each evening to rate the passed day, as regards these aspects. The scale rates each parameter from 0 (not at all) to 6 (extremely). Every day of the trial is rated. The last evening of the study (D4) the parents rated the passed day by scoring from 0-6 each of the 3 aspects of day cough. The summed score for all aspects gives the combined day cough score. This score, ranging between 0-18, was subtracted from the sum of all aspects, also ranging between 0-18, form the basal day cough score of the day before enrollment (D0). This change is recorded as change in combined day cough score and it refers to the change from D0 to D4. Negative values of the change indicate an improvement in the condition of the patient.
Time frame: 4 nights (onset of trial Night 1 to Night 4) and 3 days
Population: 78 patients were enrolled in the protective syrup Group and 72 in the carbocysteine Group. 3 patients in the protective syrup group and 6 in the carbocysteine group never began the study. 6 patients from the protective syrup group and twelve 11 patients from the carbocysteine group did not answer the questions for the last day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Protective Cough Syrup | Change in Day Cough Score at End of Study (From D0 to D4) | -6.17 change in combined day cough score | Standard Error 0.43 |
| Carbocisteine Cough Syrup | Change in Day Cough Score at End of Study (From D0 to D4) | -4.54 change in combined day cough score | Standard Error 0.6 |
p-value: <0.05t-test, 2 sided
Secondary
Change in Night Cough Score at End of Study (From N0 to N4)
A validated cough questionnaire measuring 5 aspects of night cough (frequency, severity, bothersomeness, child sleep and parents' sleep) on a 7 point Likert scale was used each morning to rate the passed night. The scale rates each parameter from 0 (not at all) to 6 (extremely). Every night of the trial is rated. The morning after the last night of the study (N4) the parents rated the passed night by scoring from 0-6 each of the 5 aspects of night cough. The summed score for all aspects gives the combined night cough score. This score, ranging between 0-30, was subtracted from the sum of all aspects, also ranging between 0-30, form the basal night cough score of the night before enrollment (N0). This change is recorded as change in combined night cough score and it refers to the change from N0 to N4. Negative values of the change indicate an improvement in the condition of the patient.
Time frame: 4 nights (onset of trial Night 1 to Night 4) and 3 days
Population: 78 patients were enrolled in the protective syrup Group and 72 in the carbocysteine Group. 3 patients in the protective syrup group and 6 in the carbocysteine group never began the study. 7 patients from the protective syrup group and twelve 12 patients from the carbocysteine group did not answer the questions for the last night.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Protective Cough Syrup | Change in Night Cough Score at End of Study (From N0 to N4) | -13.92 change in combined night cough score | Standard Error 0.92 |
| Carbocisteine Cough Syrup | Change in Night Cough Score at End of Study (From N0 to N4) | -9.48 change in combined night cough score | Standard Error 1.08 |
p-value: <0.01t-test, 2 sided