Treatment of Adults With Acute Bronchitis in the Primary Healthcare Setting

Study Overview
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Brief Summary
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The study aims to evaluate the effectiveness and safety of Atusin® CAP in reducing the severity of acute bronchitis.

Detailed Description
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A prospective, multicenter, double-blind, placebo-controlled, randomized, parallel study will be conducted to evaluate the effect of Atusin® CAP on the rapid relief of irritating cough in adults with acute bronchitis treated in actual clinical practices in primary healthcare, where patients seek help as a result of serious complaints. The combination of the three extracts: a mix of essential oils, bromelain and green Brazilian propolis may represent a breakthrough in symptomatic treatment by blocking the triggering mechanisms of cough due to acute bronchitis.

Official Title
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Phase 4, Efficacy and Safety of Atusin CAP in the Treatment of Subjects With Acute Bronchitis in the Primary Healthcare Setting: Prospective, Multicenter, Double-blind, Placebo-controlled, Randomized, Parallel-arm Clinical Study.

Conditions
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Acute Bronchitis

Intervention / Treatment
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* Dietary Supplement: Atusin CAP
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female ambulatory subjects Age of 18 to 60 years Clinical diagnosis of Acute bronchitis meeting the following criteria: ≥6 cough attacks in the day preceding the screening visit; Bronchitis Severity Scale (BSS) ≥ 5 point at screening (out of 20 points maximum); Cough severity of ≥4 on the Visual Analogue Scale (VAS) at screening Body temperature < 39.0°C Duration of symptoms ≤ 5 days before enrollment in the study; Occurrence of initial symptoms (sputum production with impaired expectoration) within 2 days prior to initiation of study treatment; Good physical and mental condition; Non-smokers (Active smoking of < 5 cigarettes per day or subjects who stopped smoking at least six months before enrollment in the study). BMI: 18,0 - 29,9 kg/m2 In the judgement of the Investigator, the subject is capable of adhere with the visit schedule, complying with study treatment regimen and completing the study. The subject has a smartphone and is capable of using it. The subject must sign an informed consent form approved by an Ethics Committee and must agree to carry out the necessary visits to the site. Exclusion Criteria: History of or current confounding respiratory disease (for example, COPD, allergic rhinitis, chronic sinusitis or chronic bronchitis - including acute exacerbations, emphysema, bronchiectasias, asthma, cystic fibrosis, tuberculosis, lung cancer, etc.); lung radiogram revealing pulmonary inflammatory lesions; suspected pneumonia - imaging diagnostics is used mainly to rule out pneumonia. ACCP 2006 Guidelines point out that an imaging assessment is not indicated in patients with symptoms of acute bronchitis, who have normal vital signs and normal pulmonary evaluation.33 Absence of the following findings reduces the likelihood of pneumonia sufficiently to eliminate the need of chest radiogram or hospital admission: heart rate > 100 beats/min; respiratory rate > 24 breaths/min; oral body temperature > 39,0 C; blood pressure: systolic < 90 mmHg, diastolic < 60 mmHg; SaO2 < 92%; If Investigator suspect pneumonia, the subject will not be enrolled in the study until the diagnosis of Pneumonia is ruled out; Concurrent bacterial infection; Elevated body temperature (> 39,5°C rectal or ≥39,0°C axillary); Subject administers antibiotics at the time of screening or for whom antibiotics are indicated, in the judgment of the Investigator; History of cough lasting over 5 days; Active smoking of ≥ 5 cigarettes per day; Hypersensitivity to the study treatment; Active concurrent disease which may interfere with subject's ability to participate in the study, in the judgement of Investigator: Sleep apnea; Elevated liver enzymes (≥ 3 times the upper limit of normal (ULN)); Severe kidney dysfunction (glomerular filtration rate < 30 mL/min); Uncontrolled diabetes mellitus (plasma glucose ≥ 250 mg/dL); Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg); Active peptic ulcer and gastrointestinal bleeding; coagulopathy; cataract(s); advanced malignant disease; significant cardiac disease (for example heart failure class III/IV, pulmonary hypertension, peripheral artery disease); Antibiotics, antivirals, steroids, anticoagulants; treatment with antitussives or expectorants in the 7 days prior to enrollment in the study; monoamine oxidase (MAO) inhibitors (for example, antidepressants, antipsychotics, or medications for Parkinson's disease) within 2 weeks prior to randomization; Subjects in poor condition requiring urgent hospitalization, or planned hospitalization during the study; Women who are pregnant or lactating; Women who plan on getting pregnant during the study; Participation in a clinical study within the last 8 weeks; Evidence or suspicion of non-compliance;; Risk of lost to follow-up; Inability to give informed consent; Alcohol or drug abuse in the last year; Unstable medical conditions, as determined by the Investigator; Inability to comply with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Interventional Model Description: Prospective, multicenter, double-blind, placebo-controlled, randomized, parallel-arm clinical study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum group<br>10 days of treatment with 3 daily doses of 420 mg (available in an capsule of 210 mg), as recommended by the manufacturer. 6 capsules daily for 10 days: 2 capsules in the morning (30 minutes before breakfast), 2 capsules at noon (30 minutes before lunch), 2 capsules in the evening (30 minutes before dinner) | Dietary Supplement: Atusin CAP<br>* This food supplement contains a distillate of 4 types of purified oils - eucalyptus, sweet orange, lemon and myrtle, rich in 1,8-cineol, limonene, alpha-pinene in the ratio: 66:32:1:1, bromelain and green Brazilian propolis in a gastro-resistant capsule. The product contains excipients: microcrystalline cellulose, silica dioxide, copovidone, magnesium stearate.<br>|
| Placebo Comparator: Placebo<br>10 days treatment with a 3-day dose of 420 mg placebo capsules (available in an indistinguishable capsule of 210 mg). 6 capsules daily for 10 days: 2 capsules in the morning (30 minutes before breakfast), 2 capsules at noon (30 minutes before lunch), 2 capsules in the evening (30 minutes before dinner) | Dietary Supplement: Placebo<br>* The placebo product will be identical in shape, appearance and color to the active product and will have the same composition but without the active ingredients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bronchitis severity assessment | The bronchitis severity assessment will be performed using the Bronchitis Severity Scale by the Investigator. The intensity of symptoms - frequency of coughing attacks, sputum discharge, rales on auscultation, chest pain on coughing and dyspnea will be assessed using a 5-point Likert scale: 0=Absent (1-2 times/day), 1=mild (3-5 times/day), 2=moderate (6-10 times/day), 3=severe (11-20 times/day), 4=very severe (>20 times/day). Clinical cure is defined as ⩾75% reduction in baseline Bronchitis Severity Scale after 10 days. | Up to 14+2 days after starting treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in cough severity | The severity of the cough by Visual Analogue Scale (VAS) is a single element measure of the subject's current perception of the severity of the cough. It is rated on a scale of 10 cm (100 mm), where 0 stands for Absent and 10 represents The most severe possible cough. The decrease in cough severity per VAS by ⩾ 20 mm is assumed to be significant in this study. | Up to 14+2 days after starting treatment | 
| Reduction of the duration (in days) of moderate to severe cough | Number of continuous days with moderate to severe cough. The severity of cough is assessed by the subject every evening at bedtime on Day 1 through Day 10, using the Visual Analogue Scale (VAS). The duration of moderate to severe cough will be calculated taking into account the number of consecutive days (2, 3,..10) in which the subject noted severity of cough of ≥ 5. | up to 14+2 days after start of treatment | 
| Frequency of daytime cough attacks | An attack is defined as a single cough of 3 or more consecutive coughs. Evaluated by: Investigator at subject enrollment, during screening at Visit 1 (V1) (Day 1), and the data will serve as a baseline, and on V2, V3 and V4 using the Bronchitis Severity Scale. Subject every evening at bedtime on Day 1 through Day 10, using an Acute Bronchitis Severity Score. | Up to 14+2 days after start of treatment | 
| Reduction in the frequency of nocturnal cough | The baseline frequency of cough attacks is evaluated by the Investigator at subject enrollment during screening Visit 1 (V1; CRF record) Day 1, using the Bronchitis Severity Scale and by the subject every evening at bedtime on Day 1 through Day 10, using the Acute Bronchitis Severity Score. The frequency of nighttime cough will be assessed daily from Day 1 (enrollment) to Day 10 and changes in its frequency will be analyzed after 1-10 days from baseline (change in day/night cough frequency after k days of treatment = frequency of day/night cough after k days of treatment - frequency of cough at enrollment (Day 1), where k = 1, 2,…,10). | Up to 10 days after the start of treatment | 
| Quality of life (QoL) | Limitation of daily activity is assessed by the Investigator at trial entry and by subject every evening at bedtime on Day 1 through Day 10 using the Acute Bronchitis Severity Score (ABSS). | Up to 10 days after start of treatment | 
| Adverse events | Incidence of mild (e.g. self-resolving), moderate (e.g. those requiring medical evaluation) and severe (e.g. those requiring prolonged hospitalization) serious and non-serious adverse events.. Recorded daily by the subjects in ePD and by Investigators in eCRF | Up to 14+2 days after starting treatment | 
| Response to treatment | At each visit during/after treatment (V2, V3 and V4), response to treatment is assessed by the Investigator using a verbal rating scale (VRS): 0 = symptoms resolved [resolved], 1 = symptoms improved compared to baseline, 2 = symptoms unchanged compared to baseline, 3 = symptoms worsened compared to baseline. Subjects with points 0 or 1 are defined as responders; subjects with points 2 or 3 were defined as non-responders. | Up to 14+2 days after starting treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mix of essential oils, Cough, Sputum, Bromelain, Green Brazilian propolis, Acute Bronchitis, Adults