Treatment of Adults With Acute Bronchitis in the Primary Healthcare Setting

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.

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

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.

Inclusion Criteria:

Male and female ambulatory subjects

1. Age of 18 to 60 years

2. 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

3. Duration of symptoms ≤ 5 days before enrollment in the study;

4. Occurrence of initial symptoms (sputum production with impaired expectoration) within 2 days prior to initiation of study treatment;

5. Good physical and mental condition;

6. Non-smokers (Active smoking of < 5 cigarettes per day or subjects who stopped smoking at least six months before enrollment in the study).

7. BMI: 18,0 - 29,9 kg/m2

8. 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.

9. The subject has a smartphone and is capable of using it.

10. 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:

1. 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;

2. Concurrent bacterial infection;

3. Elevated body temperature (> 39,5°C rectal or ≥39,0°C axillary);

4. Subject administers antibiotics at the time of screening or for whom antibiotics are indicated, in the judgment of the Investigator;

5. History of cough lasting over 5 days;

6. Active smoking of ≥ 5 cigarettes per day;

7. Hypersensitivity to the study treatment;

8. 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);

9. 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;

10. Subjects in poor condition requiring urgent hospitalization, or planned hospitalization during the study;

11. Women who are pregnant or lactating;

12. Women who plan on getting pregnant during the study;

13. Participation in a clinical study within the last 8 weeks;

14. Evidence or suspicion of non-compliance;;

15. Risk of lost to follow-up;

16. Inability to give informed consent;

17. Alcohol or drug abuse in the last year;

18. Unstable medical conditions, as determined by the Investigator;

19. Inability to comply with the study protocol.