Clinical trial NCT06142994: Treatment of Adults With Acute Bronchitis in the Primary Healthcare Setting
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Bronchitis
Keywords: Cough
Sputum
Mix of essential oils
Bromelain
Green Brazilian propolis
Acute Bronchitis
Adults
Lead sponsor: Neopharm Bulgaria Ltd.
Sponsor class: INDUSTRY
First posted: 2023-11-22
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, double-blind, placebo-controlled, randomized, parallel-arm clinical study
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Bronchitis severity assessment
timeFrame: Up to 14+2 days after starting treatment
Secondary outcomes:
measure: Reduction in cough severity
timeFrame: Up to 14+2 days after starting treatment
measure: Reduction of the duration (in days) of moderate to severe cough
timeFrame: up to 14+2 days after start of treatment
measure: Frequency of daytime cough attacks
timeFrame: Up to 14+2 days after start of treatment
measure: Reduction in the frequency of nocturnal cough
timeFrame: Up to 10 days after the start of treatment
measure: Quality of life (QoL)
timeFrame: Up to 10 days after start of treatment
measure: Adverse events
timeFrame: Up to 14+2 days after starting treatment
measure: Response to treatment
timeFrame: Up to 14+2 days after starting treatment
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: University Hospital "St George"
Study officials:
affiliation: Head of Pulmonology clinic in the UMHAT "Sveti Georgi", Medical University-Plovdiv
name: Vladimir Hodzhev, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clnic of Pneumology at UMHAT "St. Marina", Medical University - Varna
name: Diana Petkova, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Head of Pulmonology clinic in the UMHAT St Ivan Rilski, Medical University of Sofia
name: Rossen Petkov, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Head of Pneumology and Phthisiology clinic in the UMHAT "Dr. Georgi Stranski"
name: Yavor Ivanov, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clark TW, Medina MJ, Batham S, Curran MD, Parmar S, Nicholson KG. Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample. J Infect. 2014 Nov;69(5):507-15. doi: 10.1016/j.jinf.2014.07.023. Epub 2014 Aug 6.
citation: Gonzales R, Sande MA. Uncomplicated acute bronchitis. Ann Intern Med. 2000 Dec 19;133(12):981-91. doi: 10.7326/0003-4819-133-12-200012190-00014.
citation: Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan;129(1 Suppl):95S-103S. doi: 10.1378/chest.129.1_suppl.95S.
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citation: Tackett KL, Atkins A. Evidence-based acute bronchitis therapy. J Pharm Pract. 2012 Dec;25(6):586-90. doi: 10.1177/0897190012460826. Epub 2012 Oct 16.
citation: Malesker MA, Callahan-Lyon P, Ireland B, Irwin RS; CHEST Expert Cough Panel. Pharmacologic and Nonpharmacologic Treatment for Acute Cough Associated With the Common Cold: CHEST Expert Panel Report. Chest. 2017 Nov;152(5):1021-1037. doi: 10.1016/j.chest.2017.08.009. Epub 2017 Aug 22.
citation: Bagcchi S. Stigma during the COVID-19 pandemic. Lancet Infect Dis. 2020 Jul;20(7):782. doi: 10.1016/S1473-3099(20)30498-9. No abstract available.