Evaluation of Efficacy and Safety in Control Cough and the Relief of Nasal Symptoms in Children 2-12 Years Old,Suffering From Cough and Acute Rhinitis

Study Overview
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Brief Summary
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Multicenter clinical trial, phase III, controlled by active medicine, open, randomized, enroll 962 children, 2 to 12 years old, that suffer acute inflammation upper airway characterized by non-productive cough, daytime/nighttime, with duration for at least 3 and no more than 5 consecutive days (without systemic/topic use of medication during this period) followed by nasal congestion, with or without associate other nasal symptoms (sneezing, runny nose, nasal itching and/or mouth breathing). The subjects will be allocated in 2 parallel groups, and will receive the medicines of study, according of the randomization.

Official Title
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Multicenter Clinical Trial, Phase III, Controlled, Open, Parallel Group, Randomized, Comparing the Fixed Dose Combination of Diphenhydramine + Dropropizine + Pseudoephedrine and the Combined Use of Dropropizine and Fixed Dose Combination of Pseudoephedrine Hydrochloride + Brompheniramine Maleate Used Orally for Evaluation of Efficacy and Safety in Control Cough and the Relief of Nasal Symptoms in Children 2 to 12 Years Old, Suffering From Non-productive Cough and Acute Rhinitis.

Conditions
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Inflammation, Cough, Rhinitis

Intervention / Treatment
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* Drug: diphenhydramine + dropropizine + pseudoephedrine
* Drug: Dropropizine and fixed dose combination of pseudoephedrine hydrochloride + brompheniramine maleate (Dimetapp® elixir).


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 2 and 12 years old, of both sexes; Clinical condition compatible with acute rhinitis accompanied by nasal obstruction; Non-productive cough, daytime and/or nighttime with at least 3 and up 5 consecutive days in duration; Score greater than or equal to 3 points on the cough severity score (As per item 4.1.2); Score greater than or equal to 2 points on the nasal obstruction severity score (As per item 4.1.3); ICF signed by a parent/caregiver/representant; Parent/Caregiver/Representant capacity, according to investigator evaluation, for compliance at the treatment and protocol requirements, fulfilling the regular visits; Exclusion Criteria: Non-productive cough with purulent smear, fever (axillar temperature superior than 37,8°C/100°F), purulent runny nose and other signs and symptoms of bacteria infection of upper and lower airways at 7 days before the screening/randomization visit; Septal deviation level III (in any region and any nasal cavity) and/or nasal polyps or other determinants conditions of nasal congestion; Previous diagnosis of asthma; Patients under treatment for chronic allergy; Presence of purulent or mucopurulent secretion, nasal vault or mal formations (cleft lip or cleft nasolabial corrected or not) in nasal vestibule; Current use of systemic antibiotics for any reason; Use of prohibited medicine within the prescribed period before V0 as shown in item 9.3 of this protocol; Participation in last one year of clinical protocols; Any psychiatric diseases, including major depression; Presence of mental retardation from any cause; Diagnosis of renal or hepatic failure; History of hypersensitivity to any component of the study drugs; Relatives of sponsor´s or study site´s employee; Current evidence of clinically significant diseases: hematopoietic, gastrointestinal, cardiovascular, hepatic, renal, neurological, endocrine, psychiatric, autoimmune, pulmonary, or another disease that block the patient participation; Patient or parent/caregiver/representant with a history of lack of compliance to treatment or previous treatment protocols; Any finding of clinical observation (anamnesis and physical exam) laboratory abnormality (eg, blood glucose, blood count), disease (for example, liver, cardiovascular system, lung) or therapy that, in opinion of the investigator, may endanger the patient or interfere with the endpoints of study.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 12 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Notuss® syrup<br>Group 1: fixed dose combination of diphenhydramine + dropropizine + pseudoephedrine (Notuss® syrup). | Drug: diphenhydramine + dropropizine + pseudoephedrine<br>* Group 1: fixed dose combination of diphenhydramine + dropropizine + pseudoephedrine (Notuss® syrup). Posology: The medicine treat will be as follows: - Notuss® syrup Age: 2-5 years / Dosage: 5,0 mL Age: 6-12 years / Dosage: 10,0 ml<br>|
| Active Comparator: Dropropizine + Pseudoephedrine and brompheniramine<br>Group 2: combined use of dropropizine and fixed dose combination of pseudoephedrine hydrochloride + brompheniramine maleate. | Drug: Dropropizine and fixed dose combination of pseudoephedrine hydrochloride + brompheniramine maleate (Dimetapp® elixir).<br>* Dropropizine: Age: 2 - 3 years / Dosage: 5,0 ml Age: 4 - 12 years / Dosage: 10,0 ml Pseudoephedrine hydrochloride + brompheniramine maleate: Age: 2 - 3 years / Dosage: 2,5 ml Age: 4 - 6 years / Dosage: 5,0 ml Age: 7 - 9 years / Dosage: 7,5 ml Age: 10 - 12 years / Dosage: 10,0 ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of nasal congestion and cough | Participants were evaluated (by a parent/guardian/caregivers) for pain intensity by using a 4-point rating scale: 0=none, 1=mild, 2=moderate, and 3=severe. | Evaluated on the day 2 after beginning treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of nasal congestion and cough | Participants were evaluated (by a parent/guardian/caregivers) for pain intensity by using a 4-point rating scale: 0=none, 1=mild, 2=moderate, and 3=severe. | Evaluated on the 7(±1) day after beginning treatment | 
| Improvement of non-obstructive nasal symptoms | Participants were evaluated (by a parent/guardian/caregivers for pain intensity by using a sum of 4-point rating scale: 0=none, 1=mild, 2=moderate, and 3=severe. | Evaluated on the day 2 and 7 (±1) after beginning treatment | 
| Reduction of the frequency of nighttime awakenings of parent/guardian/roommate of the child |  | Evaluated on the day 2 and 7 (±1) after beginning treatment | 
| Reduction of vomiting frequency episodes triggered by coughing |  | Evaluated on the day 2 and 7 (±1) after beginning treatment | 
| Improvement of acute rhinitis signs | Assessed by anterior rhinoscopy and application of specific clinical scores | Evaluated on the day 2 and 7 (±1) after beginning treatment | 
| Use of rescue medication |  | Evaluated on the day 2 and 7 (±1) after beginning treatment | 
| Overall impression of improvement by the investigator | Specific scale and overall impression of improvement by a parent/guardian/ caregiver of the child | Evaluated on the day 2 and 7 (±1) after beginning treatment | 
| Safety descriptive about occurence of adverse events, evaluation of results of general physical examination. | Collection of safety data throughout the whole study period | Will be evaluated during the 7(± 1) days of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cough, acute rhinitis, common cold, nasal symptoms, children., Acute inflammation upper airway