Comparison of Efficacy and Tolerability of Two Cough Syrups in Cough Due to Cold in Children.

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized, Single Blind, Multicenter Study to Evaluate the Efficacy and Tolerability of Syr. Grintuss Pediatric and Syr. Mucolit in Cough Due to Upper Respiratory Tract Infection in Children

Conditions
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Cough, Upper Respiratory Tract Infection

Intervention / Treatment
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* Device: protective cough syrup
* Drug: carbocisteine cough syrup


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: protective cough syrup<br>syrup containing honey, plantago lanceolata, grindelia robusta, helichrysum italicum ina syrup form. The cough syrup is a CE marked medical device acting in a non pharmacological way to reduce cough. Dosage: 20 ml divided in three doses per day for the duration of the study (4 nights, 3 days) | Device: protective cough syrup<br>* 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.<br>* Other names: Grintuss;|
| Active Comparator: carbocisteine cough syrup<br>Dosage 20-25 mg/kg/day three times a day (3 days/4 nights) | Drug: carbocisteine cough syrup<br>* Mucolytic<br>* Other names: Lisomucil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 night from before enrollment (N0) to first night after treatment (N1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 nights (onset of trial Night 1 to Night 4) and 3 days | 
| 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. | 4 nights (onset of trial Night 1 to Night 4) and 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cough, common cold, antitussive agents, mucosal protection, medical device